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Sample records for rat substantia gelatinosa

  1. Minocycline enhances inhibitory transmission to substantia gelatinosa neurons of the rat spinal dorsal horn.

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    Peng, H-Z; Ma, L-X; Lv, M-H; Hu, T; Liu, T

    2016-04-05

    Minocycline, a second-generation tetracycline, is well known for its antibiotic, anti-inflammatory, and antinociceptive effects. Modulation of synaptic transmission is one of the analgesic mechanisms of minocycline. Although it has been reported that minocycline may suppress excitatory glutamatergic synaptic transmission, it remains unclear whether it could affect inhibitory synaptic transmission, which also plays a key role in modulating pain signaling. To examine the effect of minocycline on synaptic transmission in rat spinal substantia gelatinosa (SG) neurons, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole-cell patch-clamp recording at a holding potential of 0 mV. Bath application of minocycline significantly increased the frequency but not the amplitude of sIPSCs in a reversible and concentration-dependent manner with an EC50 of 85. The enhancement of inhibitory synaptic transmission produced by minocycline was not affected by the glutamate receptor antagonists CNQX and D-APV or by the voltage-gated sodium channel blocker tetrodotoxin (TTX). Moreover, the potency of minocycline for facilitating sIPSC frequency was the same in both glycinergic and GABAergic sIPSCs without changing their decay phases. However, the facilitatory effect of minocycline on sIPSCs was eliminated in a Ca(2+)-free Krebs solution or by co-administration with calcium channel blockers. In summary, our data demonstrate that baseline inhibitory synaptic transmission in SG neurons is markedly enhanced by minocycline. This may function to decrease the excitability of SG neurons, thus leading to a modulation of nociceptive transmission. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Activation of substantia gelatinosa by midbrain reticular stimulation demonstrated with 2-deoxyglucose in the rat spinal cord

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    Gonzales-Lima, F.

    1986-01-01

    The autoradiographic ( 14 C)2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG)(Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular mechanisms at the spinal cord level. (author)

  3. Activation of substantia gelatinosa by midbrain reticular stimulation demonstrated with 2-deoxyglucose in the rat spinal cord

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    Gonzales-Lima, F

    1986-04-24

    The autoradiographic (/sup 14/C)2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG)(Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular mechanisms at the spinal cord level. 12 refs.

  4. Contribution of presynaptic HCN channels to excitatory inputs of spinal substantia gelatinosa neurons.

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    Peng, S-C; Wu, J; Zhang, D-Y; Jiang, C-Y; Xie, C-N; Liu, T

    2017-09-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pathological pain-associated voltage-gated ion channels. They are widely expressed in central nervous system including spinal lamina II (also named the substantia gelatinosa, SG). Here, we examined the distribution of HCN channels in glutamatergic synaptic terminals as well as their role in the modulation of synaptic transmission in SG neurons from SD rats and glutamic acid decarboxylase-67 (GAD67)-GFP mice. We found that the expression of the HCN channel isoforms was varied in SG. The HCN4 isoform showed the highest level of co-localization with VGLUT2 (23±3%). In 53% (n=21/40 neurons) of the SG neurons examined in SD rats, application of HCN channel blocker, ZD7288 (10μM), decreased the frequency of spontaneous (s) and miniature (m) excitatory postsynaptic currents (EPSCs) by 37±4% and 33±4%, respectively. Consistently, forskolin (FSK) (an activator of adenylate cyclase) significantly increased the frequency of mEPSCs by 225±34%, which could be partially inhibited by ZD7288. Interestingly, the effects of ZD7288 and FSK on sEPSC frequency were replicated in non-GFP-expressing neurons, but not in GFP-expressing GABAergic SG neurons, in GAD67-GFP transgenic C57/BL6 mice. In summary, our results represent a previously unknown cellular mechanism by which presynaptic HCN channels, especially HCN4, regulate the glutamate release from presynaptic terminals that target excitatory, but not inhibitory SG interneurons. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Activation of Glycine and Extrasynaptic GABAA Receptors by Taurine on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis

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    Thi Thanh Hoang Nguyen

    2013-01-01

    Full Text Available The substantia gelatinosa (SG of the trigeminal subnucleus caudalis (Vc has been known for the processing and transmission of orofacial nociceptive information. Taurine, one of the most plentiful free amino-acids in humans, has proved to be involved in pain modulation. In this study, using whole-cell patch clamp technique, we investigated the direct membrane effects of taurine and the action mechanism behind taurine-mediated responses on the SG neurons of the Vc. Taurine showed non-desensitizing and repeatable membrane depolarizations and inward currents which remained in the presence of amino-acid receptors blocking cocktail (AARBC with tetrodotoxin, indicating that taurine acts directly on the postsynaptic SG neurons. Further, application of taurine at different doses (10 μM to 3 mM showed a concentration dependent depolarizations and inward currents with the EC50 of 84.3 μM and 723 μM, respectively. Taurine-mediated responses were partially blocked by picrotoxin (50 μM and almost completely blocked by strychnine (2 μM, suggesting that taurine-mediated responses are via glycine receptor (GlyR activation. In addition, taurine (1 mM activated extrasynaptic GABAA receptor (GABAAR-mediated currents. Taken together, our results indicate that taurine can be a target molecule for orofacial pain modulation through the activation of GlyRs and/or extrasynaptic GABAARs on the SG neurons.

  6. Activation of Glycine and Extrasynaptic GABAA Receptors by Taurine on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis

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    Bhattarai, Janardhan Prasad; Park, Soo Joung; Han, Seong Kyu

    2013-01-01

    The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) has been known for the processing and transmission of orofacial nociceptive information. Taurine, one of the most plentiful free amino-acids in humans, has proved to be involved in pain modulation. In this study, using whole-cell patch clamp technique, we investigated the direct membrane effects of taurine and the action mechanism behind taurine-mediated responses on the SG neurons of the Vc. Taurine showed non-desensitizing and repeatable membrane depolarizations and inward currents which remained in the presence of amino-acid receptors blocking cocktail (AARBC) with tetrodotoxin, indicating that taurine acts directly on the postsynaptic SG neurons. Further, application of taurine at different doses (10 μM to 3 mM) showed a concentration dependent depolarizations and inward currents with the EC50 of 84.3 μM and 723 μM, respectively. Taurine-mediated responses were partially blocked by picrotoxin (50 μM) and almost completely blocked by strychnine (2 μM), suggesting that taurine-mediated responses are via glycine receptor (GlyR) activation. In addition, taurine (1 mM) activated extrasynaptic GABAA receptor (GABAAR)-mediated currents. Taken together, our results indicate that taurine can be a target molecule for orofacial pain modulation through the activation of GlyRs and/or extrasynaptic GABAARs on the SG neurons. PMID:24379976

  7. Enhanced GABA action on the substantia gelatinosa neurons of the medullary dorsal horn in the offspring of streptozotocin-injected mice.

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    Nguyen, Hoang Thi Thanh; Bhattarai, Janardhan Prasad; Park, Soo Joung; Lee, Jeong Chae; Cho, Dong Hyu; Han, Seong Kyu

    2015-07-01

    Peripheral neuropathy is a frequent complication of diabetes mellitus and a common symptom of neuropathic pain, the mechanism of which is complex and involves both peripheral and central components of the sensory system. The lamina II of the medullary dorsal horn, called the substantia gelatinosa (SG), is well known to be a critical site for processing of orofacial nociceptive information. Although there have been a number of studies done on diabetic neuropathy related to the orofacial region, the action of neurotransmitter receptors on SG neurons in the diabetic state is not yet fully understood. Therefore, we used the whole-cell patch clamp technique to investigate this alteration on SG neurons in both streptozotocin (STZ)-induced diabetic mice and offspring from diabetic female mice. STZ (200 mg/kg)-injected mice showed a small decrease in body weight and a significant increase in blood glucose level when compared with their respective control group. However, application of different concentrations of glycine, gamma-aminobutyric acid (GABA) and glutamate on SG neurons from STZ-injected mice did not induce any significant differences in inward currents when compared to their control counterparts. On the other hand, the offspring of diabetic female mice (induced by multiple injections of STZ (40 mg/kg) for 5 consecutive days) led to a significant decrease in both body weight and blood glucose level compared to the control offspring. Glycine and glutamate responses in the SG neurons of the offspring from diabetic female mice were similar to those of control offspring. However, the GABA response in SG neurons of offspring from diabetic female mice was greater than that of control offspring. Furthermore, the GABA-mediated responses in offspring from diabetic and control mice were examined at different concentrations ranging from 3 to 1,000 μM. At each concentration, the GABA-induced mean inward currents in the SG neurons of offspring from diabetic female mice were

  8. Infusion of opiates into substantia nigra protects against maximal electroshock seizures in rats.

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    Garant, D S; Gale, K

    1985-07-01

    Microinfusion of morphine sulfate (50 nmol), [d-Ala2]-Met-enkephalin (35 nmol) or dynorphin A 1-13 (1 nmol) bilaterally into the substantia nigra significantly attenuated seizures induced by maximal electroshock in rats. This action was accompanied by stereotyped behavioral hyperactivity. These anticonvulsant and behavioral effects were antagonized by systemic naloxone administration; neither effect was observed after intranigral microinjection of dynorphin A 1-17 amide (1 nmol). These results are consistent with a mu opiate receptor-mediated inhibition of substantia nigra efferent neurons, and with the proposal that bilateral inhibition of nigral efferents attenuates seizure propagation. However, intranigral morphine failed to alter the severity of i.v. bicuculline seizures, indicating that opiate-mediated inhibition in substantia nigra is distinct from that produced by gamma-aminobutyric acid.

  9. Apelin-13 ameliorates cognitive impairments in 6-hydroxydopamine-induced substantia nigra lesion in rats.

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    Haghparast, Elham; Esmaeili-Mahani, Saeed; Abbasnejad, Mehdi; Sheibani, Vahid

    2018-04-01

    Although Parkinson's disease (PD) is well known with its motor deficits, the patients often suffer from cognitive dysfunction. Apelin, as the endogenous ligand of the APJ receptor, is found in several brain regions such as substantia nigra and mesolimbic pathway. However, the role of apelin in cognition and cognitive disorders has not been fully clarified. In this study the effects of apelin-13 were investigated on cognitive disorders in rat Parkinsonism experimental model. 6-hydroxydopamine (6-OHDA) was administrated into the substantia nigra. Apelin-13 (1, 2 and 3μg/rat) was administered into the substantia nigra one week after the 6-OHDA injection. Morris water maze (MWM), object location and novel object recognition tests were performed one month after the apelin injection. 6-OHDA-treated animals showed a significant impairment in cognitive functions which was revealed by the increased in the escape latency and traveled distance in MWM test and decreased in the exploration index in novel object recognition and object location tasks. Apelin-13 (3μg/rat) significantly attenuates the mentioned cognitive impairments in 6-OHDA-treated animals. In conclusion, the data support the pro-cognitive property of apelin-13 in 6-OHDA-induced cognitive deficit and provided a new pharmacological aspect of the neuropeptide apelin. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Edaravone protects neurons in the rat substantia nigra against 6-hydroxydopamine-induced oxidative stress damage.

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    Liu, Xiqi; Shao, Rushing; Li, Meng; Yang, Guofeng

    2014-11-01

    To investigate the mechanism of the neuroprotective effect of edaravone in substantia nigra (SN) of the 6-OHDA-induced rat model of Parkinson's disease. Animal model of Parkinson's disease was induced in male Sprague-Dawley rats by injecting 6-OHDA into the left medial forebrain bundle. Subsequently, rats were intraperitoneally injected with 0.3, 1, or 3 mg/kg of edaravone for 14 days or with 3 mg/kg edaravone for 14 days followed by 14 days of no treatment. We evaluated the effect of edaravone on the rotational and normal behavior of the rats, and on the number of tyrosine hydroxylase (TH)-positive cells, the amount of Nissl bodies, and the levels of glutathione (GSH), and malondialdehyde (MDA) in the SN. Edaravone treatment at 3 mg/kg significantly reduced apomorphine-induced rotational behavior (P Edaravone exerted a long-term neuroprotective effects in 6-OHDA-induced PD animal model by attenuating changes in the levels of GSH and MDA in SN, caused by oxidative stress. Edaravone prevented 6-OHDA-induced behavioral changes and de-pigmentation of SN that results from the loss of dopaminergic neurons.

  11. Calpain inhibition reduces NMDA receptor rundown in rat substantia nigra dopamine neurons.

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    Zhao, Jerry; Baudry, Michel; Jones, Susan

    2018-05-04

    Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca 2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca 2+ -dependent regulatory protein has not been identified. The role of the Ca 2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown. To investigate the role of the calpain-2 isoform, the membrane permeable calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I, 200 nM), was applied; C2I application significantly reduced whole cell NMDAR current rundown. Interestingly, ALLN but not C2I significantly reduced rundown of NMDA-EPSCs. These results suggest the calpain-2 isoform mediates Ca 2+ -dependent regulation of extrasynaptic NMDAR current in the first postnatal week, while calpain-1 might mediate rundown of synaptic NMDAR currents. One week later in postnatal development, at P12-P16 ('P14'), there was significantly less rundown in SNc-DA neurons, and no significant effect on rundown of either Ca 2+ chelation or treatment with the calpain inhibitor, ALLN, suggesting that the rundown observed in SNc-DA neurons from two week-old rats might be Ca 2+ -independent. In conclusion, Ca 2+ -dependent rundown of extrasynaptic NMDAR currents in SNc DA neurons involves calpain-2 activation, but Ca 2+ - and calpain-2-dependent NMDAR current rundown is developmentally regulated. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. OXIDATIVE STRESS-DEPENDENT ALTERED IMMUNE RESPONSES AND CELL DEATH IN SUBSTANTIA NIGRA AFTER OZONE EXPOSURE IN RAT

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    Selva eRivas - Arancibia

    2015-05-01

    Full Text Available Parkinson’s disease has been associated with the selective loss of neurons in the substantia nigra pars compacta. Increasing evidence suggests that oxidative stress plays a major role. The resulting increase in reactive oxygen species triggers a sequence of events that leads to cell damage, activation of microglia cells and neuroinflammatory responses. Our objective was to study whether chronic exposure to low doses of ozone, which produces oxidative stress itself, induces progressive cell death in conjunction with glial alterations in the substantia nigra. Animals were exposed to an ozone-free air stream (control or to low doses of ozone for 7, 15, 30, 60, or 90 days. Each group underwent 1 spectrophotometric analysis for protein oxidation; 2 western blot testing for microglia reactivity and nuclear factor kappa B expression levels; and 3 immunohistochemistry for cytochrome c, GFAP, Iba-1, NFkB and COX-2. Our results indicate that ozone induces an increase in protein oxidation levels, changes in activated astrocytes and microglia, and cell death. NFkB and cytochrome c showed an increase until 30 days of exposure, while cyclooxygenase 2 in the substantia nigra increased from 7 days up to 90 days of repetitive ozone exposure. These results suggest that oxidative stress caused by ozone exposure induces changes in inflammatory responses and progressive cell death in the substantia nigra in rats, which could also be occurring in Parkinson’s disease.

  13. Chronic intrastriatal dopamine infusions in rats with unilateral lesions of the substantia nigra

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    Hargraves, R.; Freed, W.J.

    1987-01-01

    This study examined the effects of continuously supplied dopamine delivered directly into the dopamine-deficient striatum. Rats received unilateral lesions of the substantia nigra by stereotaxic administration of 6-hydroxydopamine and were tested for apomorphine-induced rotational behavior and general activity. Osmotic mini-pumps were filled with dopamine in various concentrations, implanted subcutaneously and connected to a cannula implanted directly into the striatum. The system delivered solution at a rate of .5 μl/hr for two weeks. Dopamine in a dosage of 0.5 μg/per hour reduced apomorphine-induced rotational behavior by a mean of 52 +/- 5.8% (mean +/- SEM n=20) with a maximal individual decrease of 99%. There was no change in general activity or increase in stereotype behavior. Infusions of vehicle solutions did not decrease rotational behavior. Spread of the infused dopamine and its metabolites was estimated by adding 3 H-dopamine to the pumps in tracer quantities. Radioactivity was highly concentrated at the infusion site and decreased rapidly within a few mm from the infusion site. Continuous infusion methods may eventually prove to be effective in the treatment of nigro-striatal degenerative disease. 12 references, 4 figures

  14. GABAB-receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra.

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    Engberg, G; Kling-Petersen, T; Nissbrandt, H

    1993-11-01

    Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABAB-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABAB-receptor agonist baclofen (1-16 mg/kg) was associated with a dose-dependent regularization of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularization of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GABAA-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3-10 min) did neither promote nor prevent the regularization of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABAB-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst firing activity on these neurons.

  15. Acute Neuroinflammatory Response in the Substantia Nigra Pars Compacta of Rats after a Local Injection of Lipopolysaccharide

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    Yazmin M. Flores-Martinez

    2018-01-01

    Full Text Available Models of Parkinson’s disease with neurotoxins have shown that microglial activation does not evoke a typical inflammatory response in the substantia nigra, questioning whether neuroinflammation leads to neurodegeneration. To address this issue, the archetypal inflammatory stimulus, lipopolysaccharide (LPS, was injected into the rat substantia nigra. LPS induced fever, sickness behavior, and microglial activation (OX42 immunoreactivity, followed by astrocyte activation and leukocyte infiltration (GFAP and CD45 immunoreactivities. During the acute phase of neuroinflammation, pro- and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-4, and IL-10 responded differentially at mRNA and protein level. Increased NO production and lipid peroxidation occurred at 168 h after LPS injection. At this time, evidence of neurodegeneration could be seen, entailing decreased tyrosine hydroxylase (TH immunoreactivity, irregular body contour, and prolongation discontinuity of TH+ cells, as well as apparent phagocytosis of TH+ cells by OX42+ cells. Altogether, these results show that LPS evokes a typical inflammatory response in the substantia nigra that is followed by dopaminergic neurodegeneration.

  16. Acute Neuroinflammatory Response in the Substantia Nigra Pars Compacta of Rats after a Local Injection of Lipopolysaccharide

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    Gonzalez-Barrios, Juan A.; Gutierrez-Castillo, Maria E.

    2018-01-01

    Models of Parkinson's disease with neurotoxins have shown that microglial activation does not evoke a typical inflammatory response in the substantia nigra, questioning whether neuroinflammation leads to neurodegeneration. To address this issue, the archetypal inflammatory stimulus, lipopolysaccharide (LPS), was injected into the rat substantia nigra. LPS induced fever, sickness behavior, and microglial activation (OX42 immunoreactivity), followed by astrocyte activation and leukocyte infiltration (GFAP and CD45 immunoreactivities). During the acute phase of neuroinflammation, pro- and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-4, and IL-10) responded differentially at mRNA and protein level. Increased NO production and lipid peroxidation occurred at 168 h after LPS injection. At this time, evidence of neurodegeneration could be seen, entailing decreased tyrosine hydroxylase (TH) immunoreactivity, irregular body contour, and prolongation discontinuity of TH+ cells, as well as apparent phagocytosis of TH+ cells by OX42+ cells. Altogether, these results show that LPS evokes a typical inflammatory response in the substantia nigra that is followed by dopaminergic neurodegeneration. PMID:29854828

  17. Does the cerebral cortex exacerbate dopaminergic cell death in the substantia nigra of 6OHDA-lesioned rats?

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    Luquin, Natasha; Mitrofanis, John

    2008-01-01

    We have explored the survival of dopaminergic cells of the substantia nigra pars compacta (SNc) in 6 hydroxydopamine (6OHDA)-lesioned rats with prior cortical removal. There were approximately 35% more dopaminergic cells in the ventral sector of SNc (vSNc) of 6OHDA-lesioned rats that had prior cortical removal compared to those that did not. By contrast, there were no differences in dopaminergic cell number between these experimental groups in the ventral tegmental area (VTA) and the dorsal sector of SNc (dSNc). Hence, prior cortical removal in 6OHDA-lesioned rats neuroprotected vSNc--but not VTA or dSNc--dopaminergic cells from death.

  18. High density of benzodiazepine binding sites in the substantia innominata of the rat

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    Sarter, M.; Schneider, H.H.

    1988-01-01

    In order to study the neuronal basis of the pharmacological interactions between benzodiazepine receptor ligands and cortical cholinergic turnover, we examined the regional distribution of specific benzodiazepine binding sites using in vitro autoradiography. In the basal forebrain, the substantia innominata contained a high density of [ 3 H]lormetazepam (LMZ) binding sites (Bmax = 277 fmol/mg tissue; Kd = 0.55 nM). The label could be displaced by diazepam (IC50 = 100 nM), the benzodiazepine receptor antagonist beta-carboline ZK 93426 (45 nM) and the partial inverse agonist beta-carboline FG 7142 (540 nM). It is hypothesized that the amnesic effects of benzodiazepine receptor agonists are exerted through benzodiazepine receptors which are situated on cholinergic neurons in the substantia innominata and are involved in a tonic inhibition of cortical acetylcholine release. The benzodiazepine receptor antagonist ZK 93426 may exert its nootropic effects via benzodiazepine receptors in the substantia innominata and, consequently, by disinhibiting cortical acetylcholine release

  19. Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats.

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    Viggiano, Andrea; Stoddard, Madison; Pisano, Simone; Operto, Francesca Felicia; Iovane, Valentina; Monda, Marcellino; Coppola, Giangennaro

    2016-07-01

    The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats.

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    Ghazaleh Samoudi

    Full Text Available BACKGROUND: The vestibular system is connected to spinal, cerebellar and cerebral motor control structures and can be selectively activated with external electrodes. The resulting sensation of disturbed balance can be avoided by using stochastic stimulation patterns. Adding noise to the nervous system sometimes improves function. Small clinical trials suggest that stochastic vestibular stimulation (SVS may improve symptoms in Parkinson's disease. We have investigated this claim and possible mechanisms using the 6-hydroxydopamine (6-OHDA hemilesion model of Parkinson's disease. METHODOLOGY/PRINCIPAL FINDINGS: Animals were tested in the accelerating rod test and the Montoya staircase test of skilled forelimb use. In 6-OHDA hemilesioned animals, SVS improved rod performance by 56±11 s. At group level L-DOPA treatment had no effect, but positive responders improved time on rod by 60±19 s. Skilled forelimb use was not altered by SVS. To investigate how SVS may influence basal ganglia network activity, intracerebral microdialysis was employed in four regions of interest during and after SVS. In presence of the γ-amino buturic acid (GABA transporter inhibitor NNC 711, SVS induced an increase in GABA to 150±15% of baseline in the substantia nigra (SN of unlesioned animals, but had no effect in the pedunculopontine nucleus (PPN, the striatum or the ventromedial thalamus (VM. Dopamine release remained stable in all areas, as did GABA and amine concentrations in the SN of unstimulated controls. Following SVS, a sustained increase in GABA concentrations was observed in the ipsilesional, but not in the contralesional SN of 6-OHDA hemilesioned rats. In contrast, L-DOPA treatment produced a similar increase of GABA in the ipsi- and contra-lesional SN. CONCLUSIONS/SIGNIFICANCE: SVS improves rod performance in a rat model of Parkinson's disease, possibly by increasing nigral GABA release in a dopamine independent way. We propose that SVS could be useful for

  1. Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats.

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    Pang, Y; Lin, S; Wright, C; Shen, J; Carter, K; Bhatt, A; Fan, L-W

    2016-03-24

    Protection of substantia nigra (SN) dopaminergic (DA) neurons by neurotrophic factors (NTFs) is one of the promising strategies in Parkinson's disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer's patients. In vitro, insulin has been shown to protect neurons against various insults. Therefore, the current study was designed to test whether intranasal insulin could afford neuroprotection in the 6-hydroxydopamine (6-OHDA)-based rat PD model. 6-OHDA was injected into the right side of striatum to induce a progressive DA neuronal lesion in the ipsilateral SN pars compact (SNc). Recombinant human insulin was applied intranasally to rats starting from 24h post lesion, once per day, for 2 weeks. A battery of motor behavioral tests was conducted on day 8 and 15. The number of DA neurons in the SNc was estimated by stereological counting. Our results showed that 6-OHDA injection led to significant motor deficits and 53% of DA neuron loss in the ipsilateral side of injection. Treatment with insulin significantly ameliorated 6-OHDA-induced motor impairments, as shown by improved locomotor activity, tapered/ledged beam-walking performance, vibrissa-elicited forelimb-placing, initial steps, as well as methamphetamine-induced rotational behavior. Consistent with behavioral improvements, insulin treatment provided a potent protection of DA neurons in the SNc against 6-OHDA neurotoxicity, as shown by a 74.8% increase in tyrosine hydroxylase (TH)-positive neurons compared to the vehicle group. Intranasal insulin treatment did not affect body weight and blood glucose levels. In conclusion, our study showed that intranasal insulin provided strong

  2. Iptakalim inhibits nicotinic acetylcholine receptor-mediated currents in dopamine neurons acutely dissociated from rat substantia nigra pars compacta.

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    Hu, J; DeChon, J; Yan, K C; Liu, Q; Hu, G; Wu, J

    2006-07-31

    Iptakalim hydrochloride, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, has shown remarkable antihypertensive and neuroprotective effects in a variety of studies using in vivo and in vitro preparations. We recently found that iptakalim blocked human alpha4-containing nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the human SH-EP1 cell line. In the present study, we examined the effects of iptakalim on several neurotransmitter-induced current responses in single DA neurons freshly dissociated from rat substantia nigra pars compacta (SNc), using perforated patch-clamp recordings combined with a U-tube rapid drug application. In identified DA neurons under voltage-clamp configuration, glutamate-, NMDA-, and GABA-induced currents were insensitive to co-application with iptakalim (100 microM), while whole-cell currents induced by ACh (1 mM+1 microM atropine) or an alpha4beta2 nicotinic acetylcholine receptors relatively selective agonist, RJR-2403 (300 microM), were eliminated by iptakalim. Iptakalim inhibited RJR-2403-induced current in a concentration-dependent manner, and reduced maximal RJR-2403-induced currents at the highest agonist concentration, suggesting a non-competitive block. In current-clamp mode, iptakalim failed to affect resting membrane potential and spontaneous action potential firing, but abolished RJR-2403-induced neuronal firing acceleration. Together, these results indicate that in dissociated SNc DA neurons, alpha4-containing nAChRs, rather than ionotropic glutamate receptors, GABA(A) receptors or perhaps K-ATP channels are the sensitive targets to mediate iptakalim's pharmacological roles.

  3. State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats.

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    Brazhnik, Elena; Cruz, Ana V; Avila, Irene; Wahba, Marian I; Novikov, Nikolay; Ilieva, Neda M; McCoy, Alex J; Gerber, Colin; Walters, Judith R

    2012-06-06

    Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, 7 d after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8-25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25-40 Hz band with a peak frequency at 30-35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons, and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25-40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity.

  4. Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra

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    Purves-Tyson Tertia D

    2012-08-01

    Full Text Available Abstract Background Increased risk of schizophrenia in adolescent males indicates that a link between the development of dopamine-related psychopathology and testosterone-driven brain changes may exist. However, contradictions as to whether testosterone increases or decreases dopamine neurotransmission are found and most studies address this in adult animals. Testosterone-dependent actions in neurons are direct via activation of androgen receptors (AR or indirect by conversion to 17β-estradiol and activation of estrogen receptors (ER. How midbrain dopamine neurons respond to sex steroids depends on the presence of sex steroid receptor(s and the level of steroid conversion enzymes (aromatase and 5α-reductase. We investigated whether gonadectomy and sex steroid replacement could influence dopamine levels by changing tyrosine hydroxylase (TH protein and mRNA and/or dopamine breakdown enzyme mRNA levels [catechol-O-methyl transferase (COMT and monoamine oxygenase (MAO A and B] in the adolescent male rat substantia nigra. We hypothesized that adolescent testosterone would regulate sex steroid signaling through regulation of ER and AR mRNAs and through modulation of aromatase and 5α-reductase mRNA levels. Results We find ERα and AR in midbrain dopamine neurons in adolescent male rats, indicating that dopamine neurons are poised to respond to circulating sex steroids. We report that androgens (T and DHT increase TH protein and increase COMT, MAOA and MAOB mRNAs in the adolescent male rat substantia nigra. We report that all three sex steroids increase AR mRNA. Differential action on ER pathways, with ERα mRNA down-regulation and ERβ mRNA up-regulation by testosterone was found. 5α reductase-1 mRNA was increased by AR activation, and aromatase mRNA was decreased by gonadectomy. Conclusions We conclude that increased testosterone at adolescence can shift the balance of sex steroid signaling to favor androgenic responses through promoting

  5. Biochemical evidence for. gamma. -aminobutyrate containing fibres from the nucleus accumbens to the substantia nigra and ventral tegmental area in the rat

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    Walaas, I; Fonnum, F

    1980-01-01

    Glutamate decarboxylase activity, a specific marker for ..gamma..-aminobutyrate-containing neurons, has been analysed in microdissected samples from rat mesencephalon following unilateral electrocoagulations of the nucleus accumbens. This lesion resulted in a consistent decrease of 50% in the enzyme activity in the rostromedial substantia nigra, and a slight, but insignificant decrease (- 15%) in the medial parts of the caudal pars compacta of the substantia nigra. No change was found in the lateral pars compacta or the central pars reticulata. In the ventral tegmental area, the highest activity was found in the rostromedial part, adjacent to the mammillary body. At this level, a significant decrease of 20% was found in the ventral tegmental area on the lesioned side. In contrast, the activities in the medial accessory optic nucleus and the caudal ventral tegmental area adjacent to the interpenduncular nucleus were unchanged. The results indicate that the nucleus accumbens sends ..gamma..-aminobutyrate-containing fibres to the rostromedial substantia nigra and to the rostral ventral tegmental area. The caudal ventral tegmental area, the lateral pars compacta and the central pars reticulata do not receive measurable amounts of such fibres.

  6. Vitamin B12-impaired metabolism produces apoptosis and Parkinson phenotype in rats expressing the transcobalamin-oleosin chimera in substantia nigra.

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    Carlos Enrique Orozco-Barrios

    Full Text Available BACKGROUND: Vitamin B12 is indispensable for proper brain functioning and cytosolic synthesis of S-adenosylmethionine. Whether its deficiency produces effects on viability and apoptosis of neurons remains unknown. There is a particular interest in investigating these effects in Parkinson disease where Levodopa treatment is known to increase the consumption of S-adenosylmethionine. To cause deprivation of vitamin B12, we have recently developed a cell model that produces decreased synthesis of S-adenosylmethionine by anchoring transcobalamin (TCII to the reticulum through its fusion with Oleosin (OLEO. METHODOLOGY: Gene constructs including transcobalamin-oleosin (TCII-OLEO and control constructs, green fluorescent protein-transcobalamin-oleosin (GFP-TCII-OLEO, oleosin-transcobalamin (OLEO-TCII, TCII and OLEO were used for expression in N1E-115 cells (mouse neuroblastoma and in substantia nigra of adult rats, using a targeted transfection with a Neurotensin polyplex system. We studied the viability and the apoptosis in the transfected cells and targeted tissue. The turning behavior was evaluated in the rats transfected with the different plasmids. PRINCIPAL FINDINGS: The transfection of N1E-115 cells by the TCII-OLEO-expressing plasmid significantly affected cell viability and increased immunoreactivity of cleaved Caspase-3. No change in propidium iodide uptake (used as a necrosis marker was observed. The transfected rats lost neurons immunoreactive to tyrosine hydroxylase. The expression of TCII-OLEO was observed in cells immunoreactive to tyrosine hydroxylase of the substantia nigra, with a superimposed expression of cleaved Caspase-3. These cellular and tissular effects were not observed with the control plasmids. Rats transfected with TCII-OLEO expressing plasmid presented with a significantly higher number of turns, compared with those transfected with the other plasmids. CONCLUSIONS/SIGNIFICANCE: In conclusion, the TCII-OLEO transfection

  7. Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and (14C)2-deoxy-D-glucose autoradiography. [Rats

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    Schmidt, R H; Ingvar, M; Lindvall, O; Stenevi, U; Bjoerklund, A

    1982-03-01

    Dopaminergic innervation of the caudate nucleus in adult rats can be partially restored by the grafting of embryonic substantia nigra into the overlying parietal cortex with concomitant compensation of certain behavioral abnormalities. In this study the function of such grafts was investigated neurochemically by quantification of transmitter metabolism and glucose utilization in the reinnervated target. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle received a single graft to the dorsal caudate-putamen and were screened for rotational behavior following 5 mg/kg methamphetamine. The grafts restored dopamine concentrations in the caudate-putamen from initially less than 0.5% to an average of 13.6% of normal in rats with behavioral compensation. The ratio of 3,4-dihydroxyphenylacetic acid to dopamine, which is a measure of the rate of transmitter turnover, were equivalent in transplanted and normal control rats. Moreover, measurements of DOPA accumulation for a 30-min period after DOPA decarboxylase inhibition indicated similar fractional dopamine turnover rates in normal and transplant-reinnervated tissues. Correlations between rotational behavior and dopamine concentrations showed that reinnervation to only 3% of normal was sufficient to counterbalance the motor asymmetry. Measurements of glucose utilization by (14C)deoxyglucose autoradiography indicated equivalent metabolic rates for the grafted tissue and the intact substantia nigra. Overall the results indicate that behaviorally functional neuronal grafts spontaneously metabolize dopamine and utilize glucose at rates characteristic of the intact nigrostriatal system. This provides further evidence that ectopic intracortical nigral transplants can reinstate dopaminergic neurotransmission in regions of the host brain initially denervated by the 6-hydroxydopamine lesion.

  8. Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis.

    Science.gov (United States)

    Toti, Luca; Travagli, R Alberto

    2014-11-15

    Idiopathic Parkinson's disease (PD) is a late-onset, chronic, and progressive motor dysfunction attributable to loss of nigrostriatal dopamine neurons. Patients with PD experience significant gastrointestinal (GI) issues, including gastroparesis. We aimed to evaluate whether 6-hydroxy-dopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) induces gastric dysmotility via dysfunctions of the brain-gut axis. 6-OHDA microinjection into the SNpc induced a >90% decrease in tyrosine hydroxylase-immunoreactivity (IR) on the injection site. The [13C]-octanoic acid breath test showed a delayed gastric emptying 4 wk after the 6-OHDA treatment. In control rats, microinjection of the indirect sympathomimetic, tyramine, in the dorsal vagal complex (DVC) decreased gastric tone and motility; this inhibition was prevented by the fourth ventricular application of either a combination of α1- and α2- or a combination of D1 and D2 receptor antagonists. Conversely, in 6-OHDA-treated rats, whereas DVC microinjection of tyramine had reduced effects on gastric tone or motility, DVC microinjection of thyrotropin-releasing hormone induced a similar increase in motility as in control rats. In 6-OHDA-treated rats, there was a decreased expression of choline acetyl transferase (ChAT)-IR and neuronal nitric oxide synthase (NOS)-IR in DVC neurons but an increase in dopamine-β-hydroxylase-IR in the A2 area. Within the myenteric plexus of the esophagus, stomach, and duodenum, there were no changes in the total number of neurons; however, the percentage of NOS-IR neurons increased, whereas that of ChAT-IR decreased. Our data suggest that the delayed gastric emptying in a 6-OHDA rat model of PD may be caused by neurochemical and neurophysiological alterations in the brain-gut axis. Copyright © 2014 the American Physiological Society.

  9. Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra.

    Science.gov (United States)

    Newman-Tancredi, A; Cussac, D; Brocco, M; Rivet, J M; Chaput, C; Touzard, M; Pasteau, V; Millan, M J

    2001-11-30

    Unilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra pars compacta (SNPC) neurons in rats induce behavioural hypersensitivity to dopaminergic agonists. However, the role of specific dopamine receptors is unclear, and potential alterations in their transduction mechanisms remain to be evaluated. The present study addressed these issues employing the dopaminergic agonist, quinelorane, which efficaciously stimulated G-protein activation (as assessed by [35S]GTPgammaS binding) at cloned hD2 (and hD3) receptors. At rat striatal membranes, dopamine stimulated [35S]GTPgammaS binding by 1.9-fold over basal, but its actions were only partially reversed by the selective D2/D3 receptor antagonist, raclopride, indicating the involvement of other receptor subtypes. In contrast, quinelorane-induced stimulation (48% of the effect of dopamine) was abolished by raclopride, and by the D2 receptor antagonist, L741,626. Further, novel antagonists selective for D3 and D4 receptors, S33084 and S18126, respectively, blocked the actions of quinelorane at concentrations corresponding to their affinities for D2 receptors. Quinelorane potently induced contralateral rotation in unilaterally 6-OHDA-lesioned rats, an effect abolished by raclopride and L741,626, but not by D3 and D4 receptor-selective doses of S33084 and S18126, respectively. In functional ([35S]GTPgammaS) autoradiography experiments, quinelorane stimulated G-protein activation in caudate putamen and, to a lesser extent, in nucleus accumbens and cingulate cortex of naive rats. In unilaterally SNPC-lesioned rats, quinelorane-induced G-protein activation in the caudate putamen on the non-lesioned side was similar to that seen in naive animals (approximately 50% stimulation), but significantly greater on the lesioned side (approximately 80%). This increase was both pharmacologically and regionally specific since it was reversed by raclopride, and was not observed in nucleus accumbens or cingulate cortex. In conclusion

  10. Inhibition of Cathepsins B Induces Neuroprotection Against Secondary Degeneration in Ipsilateral Substantia Nigra After Focal Cortical Infarction in Adult Male Rats

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    Xialin Zuo

    2018-05-01

    Full Text Available Stroke is the leading cause of adult disability in the world. In general, recovery from stroke is incomplete. Accumulating evidences have shown that focal cerebral infarction leads to dynamic trans-neuronal degeneration in non-ischemic remote brain regions, with the disruption of connections to synapsed neurons sustaining ischemic insults. Previously, we had reported that the ipsilateral striatum, thalamus degenerated in succession after permanent distal branch of middle cerebral artery occlusion (dMCAO in Sprague-Dawley (SD rats and cathepsin (Cath B was activated before these relay degeneration. Here, we investigate the role of CathB in the secondary degeneration of ipsilateral substantia nigra (SN after focal cortical infarction. We further examined whether the inhibition of CathB with L-3-trans-(Propyl-carbamoyloxirane-2-carbonyl-L-isoleucyl-L-proline methyl ester (CA-074Me would attenuate secondary degeneration through enhancing the cortico-striatum-nigral connections and contribute to the neuroprotective effects. Our results demonstrated that secondary degeneration in the ipsilateral SN occurred and CathB was upregulated in the ipsilateral SN after focal cortical infarction. The inhibition of CathB with CA-074Me reduced the neuronal loss and gliosis in the ipsilateral SN. Using biotinylated dextran amine (BDA or pseudorabies virus (PRV 152 as anterograde or retrograde tracer to trace striatum-nigral and cortico-nigral projections pathway, CA-074Me can effectively enhance the cortico-striatum-nigral connections and exert neuroprotection against secondary degeneration in the ipsilateral SN after cortical ischemia. Our study suggests that the lysosomal protease CathB mediates the secondary damage in the ipsilateral SN after dMCAO, thus it can be a promising neuroprotective target for the rehabilitation of stroke patients.

  11. Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

    International Nuclear Information System (INIS)

    Hei, Ming-Yan; Luo, Ya-Li; Zhang, Xiao-Chun; Liu, Hong; Gao, Ru; Wu, Jing-Jiang

    2011-01-01

    Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8% O 2 /92% N 2 ) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI

  12. Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

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    Hei Ming-Yan

    2012-01-01

    Full Text Available Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI, and severe HI groups (N = 10 in each group at each time on postnatal day 7 (P7 to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH in the substantia nigra (SN. The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2 for 90 and 150 min, respectively. The elevated plus-maze (EPM test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05. The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2% and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05. The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.

  13. THE EFFECT OF BETA GLUCAN OF SACCHAROMYCES CEREVISAE ON THE INCREASE OF THE NUMBER OF BRAIN CELLS IN SUBSTANTIA NIGRA BRAIN OF PARKINSON’S WISTAR STRAIN RAT (RATTUS NORVEGICUS MODEL INDUCED WITH ROTENONE

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    Masruroh Rahayu

    2015-01-01

    Full Text Available ackground and aims. One of many neurodegenerative diseases afflicting the elderly is Parkinson. Beta glucan from Saccharomyces cerevisae is very potential to be used as a regenerative therapy of Parkinson's disease. Beta glucan can increase the mobilization of hematopoietic stem cells (HSCs from the bone marrow into the damaged tissues. Hematopoietic stem cells (HSCs which have been mobilized can regenerate and differentiate into brain cells so that the symptoms of Parkinson would be reduced. This research aims to find out the effects of the addition of Saccharomyces cerevisae toward the number of brain cells in substantia nigra Parkinson’s rat model. Method. The research was experimental in vivo using the draft of randomized post test only controlled group design. There were five groups that become the sample in this research with 5 rats for each group, i.e. negative control group, positive control group, Treatment Group 1, 2 and 3 (Rotenone + Saccharomyces cerevisae 18 mg/kgBB, 36 mg/kgBB, 72 mg/kgBBfor 4 weeks. Variable measured in this study was the number of brain cells in substantia nigra. The results of this study showed that Treatment Group 3 (72 mg/kgBB was a group with the largest number of brain cells than the other treatment groups. Statistical data obtained showed that the average number of brain cells in negative control group was 192.00 cells; positive control amounted to 116.80 cells; Treatment 1 amounted to 135.40 cells; Treatment 2 amounted to 140.80 cells; and Treatment 3 amounted to 161.80 cells. Result. The result of ANOVA test showed a significant difference between groups (p< 0.05, while the correlation test result indicated a strong correlation between the dose of Saccharomyces cerevisae and the number of substantia nigra of rat’s brain cells (r = 0,818. Conclusion. From this research, it can be concluded that the addition of Saccharomyces cerevisae with a dose of 18mg/kgBB, 36mg/kgBBdan 72 mg/kgBB is able to increase

  14. Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata

    International Nuclear Information System (INIS)

    Aceves, J.; Young, J.M.; Arias-Montano, J.A.; Floran, B.; Garcia, M.

    1997-01-01

    The release of [ 3 H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K + from 6 to 15 mM in the presence of 10 μM sulpiride was inhibited by 73±3% by 1 μM SCH 23390, consistent with a large component of release dependent upon D 1 receptor activation. The histamine H 3 receptor-selective agonist immepip (1 μM) and the non-selective agonist histamine (100 μM) inhibited [ 3 H]GABA release by 78±2 and 80±2%, respectively. The inhibition by both agonists was reversed by the H 3 receptor antagonist thioperamide (1 μM). However, in the presence of 1 μM SCH 23390 depolarization-induced release of [ 3 H]GABA was not significantly decreased by 1 μM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [ 3 H]GABA, but in the presence of 1 μM SKF 38393, which produced a 7±1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 μM) also inhibited the depolarization-induced release of [ 3 H]dopamine from substantia nigra pars reticulata slices, by 38±3%.The evidence is consistent with the proposition that activation of histamine H 3 receptors leads to the selective inhibition of the component of depolarization-induced [ 3 H]GABA release in substantia nigra pars reticulata slices which is dependent upon D 1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [ 3 H]dopamine release. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  15. Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10

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    Sridhar TS

    2009-07-01

    Full Text Available Abstract Background Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Results Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Conclusion Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of Parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

  16. Glycine receptors in the human substantia nigra as defined by (3H)strychnine binding

    Energy Technology Data Exchange (ETDEWEB)

    de Montis, G; Beaumont, K; Javoy-Agid, F; Agid, Y; Constandinidis, J; Lowenthal, A; Lloyd, K G

    1982-03-01

    Specific (3H)strychnine binding was used to identify the glycine receptor macromolecular complex in human spinal cord, substantia nigra, inferior olivary nucleus, and cerebral cortex. In material from control patients a high-affinity KD (3--8 nM) was observed in the spinal cord and the substantia nigra, both the pars compacta and the pars reticulata. This is very similar to the values observed in the rat and bovine spinal cord (8 and 3 nM, respectively) and rat substantia nigra (12 nM). In the human brain the distribution of (3H)strychnine binding (at 10 nM) was: spinal cord . substantia nigra, pars compacta greater than substantia nigra, pars reticulata . inferior olivary nucleus greater than cerebral cortex. The binding capacity (Bmax) of the rat brain (substantia nigra or spinal cord) was approximately 10-fold that of the human brain. (3H)Strychnine binding was significantly decreased in the substantia nigra from Parkinson's disease patients, both in the pars compacta (67% of control) and the pars reticulata (50% of control), but not in the inferior olivary nucleus. The results were reproduced in preliminary experiment in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. In the substantia nigra from patients who died with Huntington's disease, (3H)strychnine binding tended to be high (150% of control, NS) in both the pars compacta and the reticulata. (3H)Strychnine binding was unaltered in the substantia nigra of patients with senile dementia. Together with previous neurophysiological and neuropharmacological findings, those results support the hypothesis of glycine receptors occurring on dopamine cell bodies and/or dendrites in the substantia nigra.

  17. Effects of mild running on substantia nigra during early neurodegeneration.

    Science.gov (United States)

    Almeida, Michael F; Silva, Carolliny M; Chaves, Rodrigo S; Lima, Nathan C R; Almeida, Renato S; Melo, Karla P; Demasi, Marilene; Fernandes, Tiago; Oliveira, Edilamar M; Netto, Luis E S; Cardoso, Sandra M; Ferrari, Merari F R

    2018-06-01

    Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H 2 O 2 increase during early neurodegeneration, although the involved mechanism remains to be elucidated. TrkB levels and its anterograde trafficking seem not to be influenced by moderate treadmill running. In conclusion, moderate physical training could prevent early neurodegeneration in substantia nigra through the improvement of autophagy and mitophagy.

  18. Electrical stimulation of the substantia nigra reticulata : Detection of neuronal extracellular GABA in the ventromedial thalamus and its regulatory mechanism using microdialysis in awake rats

    NARCIS (Netherlands)

    Timmerman, W; Westerink, B.H.C.

    A combination of electrical stimulation and microdialysis was used to study the nigrothalamic gamma aminobutyric acid (GABA)ergic system and its regulatory mechanisms in awake rats. Extracellular GABA levels in the ventromedial nucleus of the thalamus were detected in S-min fractions collected

  19. Estudo comparativo entre as esferas de silicone gelatinosas e rígidas em cavidade eviscerada de coelho

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    Mayumi Shirota Kanamura

    2012-06-01

    Full Text Available OBJETIVO: Avaliar e comparar a biocompatibilidade de esferas de silicone gelatinosas e rígidas em cavidades evisceradas de coelhos. MÉTODOS: Trinta coelhos tiveram o olho direito eviscerado com implantação de esferas de silicone gelatinosas (Grupo I ou rígidas (Grupo II. Foi realizada avaliação clínica diária, ultrassonografia da cavidade orbitária, análise histológica e morfométrica da pseudocápsula que se formou ao redor dos implantes aos 7, 30 e 90 dias após a cirurgia, com avaliação estatística dos resultados. RESULTADOS: Houve boa integração das esferas com os tecidos orbitários e semelhança de resposta tecidual com ambas as esferas. Duas esferas de silicone gelatinosas e uma rígida extruíram. A pseudocápsula que se formou ao redor das esferas gelatinosas foi mais organizada, com espessura e reação inflamatória menores que a observada nas esferas rígidas. CONCLUSÕES: Esferas de silicone gelatinosas e rígidas tiveram boa integração tecidual em cavidades evisceradas de coelhos.

  20. Substantia innominata: MR findings in Parkinson's disease

    International Nuclear Information System (INIS)

    Oikawa, Hirobumi; Ehara, Shigeru; Sasaki, Makoto; Abe, Takashi

    2004-01-01

    To elucidate MR imaging changes of the substantia innominata in Parkinson's disease (PD), using a 1.5-T superconductive MR unit, the thickness of the substantia innominata was measured on coronal thin-section images in 44 PD patients and 20 age-matched control subjects. We also evaluated the correlation between the thickness of the substantia innominata and mental status in PD patients. Mean thickness of the substantia innominata was 2.3 mm in PD patients, and 2.5 mm in control subjects. Thinning of the substantia innominata was statistically significant in PD patients compared with control subjects, although there were large overlaps. Among the PD patients, thinning was remarkable in cases with dementia. A positive correlation between thickness of substantia innominata and score of Mini-Mental-Status-Examination was also observed in PD patients. Atrophy of the substantia innominata was demonstrated, especially in PD patients with cognitive impairment, on coronal MR images, and this is compatible with the previous pathological reports. (orig.)

  1. Autoradiographic localization of (125I-Tyr4)bombesin-binding sites in rat brain

    International Nuclear Information System (INIS)

    Zarbin, M.A.; Kuhar, M.J.; O'Donohue, T.L.; Wolf, S.S.; Moody, T.W.

    1985-01-01

    The binding of ( 125 I-Tyr 4 )bombesin to rat brain slices was investigated. Radiolabeled (Tyr 4 )bombesin bound with high affinity (K/sub d/ . 4 nM) to a single class of sites (B/sub max/ . 130 fmol/mg of protein); the ratio of specific to nonspecific binding was 6/1. Also, pharmacology studies indicated that the C-terminal of bombesin was important for the high affinity binding activity. Autoradiographic studies indicated that the ( 125 I-Tyr4)bombesin-binding sites were discretely distributed in certain gray but not white matter regions of rat brain. Highest grain densities were present in the olfactory bulb and tubercle, nucleus accumbens, suprachiasmatic and periventricular nuclei of the hypothalamus, central medial thalamic nucleus, medial amygdaloid nucleus, hippocampus, dentate gyrus, subiculum, nucleus of the solitary tract, and substantia gelatinosa. Moderate grain densities were present in the parietal cortex, deep layers of the neocortex, rhinal cortex, caudate putamen, stria terminalis, locus ceruleus, parabrachial nucleus, and facial nucleus. Low grain densities were present in the globus pallidus, lateral thalamus, and midbrain. Negligible grain densities were present in the cerebellum, corpus callosum, and all regions treated with 1 microM unlabeled bombesin. The discrete regional distribution of binding suggests that endogenous bombesin-like peptides may function as important regulatory agents in certain brain loci

  2. Long-term effects of ionizing radiation on the rat spinal cord: intramedullary connective tissue formation

    International Nuclear Information System (INIS)

    Gilmore, S.A.

    1973-01-01

    Light microscopy was used to evaluate the effects of ionizing radiation on spinal cords of rats irradiated when three days of age and killed at intervals up to 28 months after irradiation. The amounts of x-rays administered (2,000 R; 1,000 R; 500 R) were those which had been demonstrated by short-term studies to cause either no histopathologic changes or only transient, reparable alterations. The most significant and previously unreported finding was the development, usually restricted to the gray matter, of elongated, spindle-shaped cells that produce prodigious amounts of fibers clearly demonstrated by the Wilder's reticular stain. In cases where extensive cellular development had occurred, these cells were oriented around the perikarya of the large ventral motor neurons and formed a well-developed capsule of reticular fibers. This phenomenon occurred more frequently in rats receiving the greater amounts of radiation and killed 12 months or more after exposure. The other observation of interest was the development of lesser amounts of connective tissue-producing cells in the dorsal gray matter, where these cells were seen initially in the substantia gelatinosa. The significance of these changes is discussed in relation to previously reported long-term effects of ionizing radiation on the central nervous system

  3. TRPA1 in the spinal dorsal horn is involved in post-inflammatory visceral hypersensitivity: in vivo study using TNBS-treated rat model

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    Li Q

    2016-12-01

    Full Text Available Qian Li,1,* Cheng-Hao Guo,2,* Mohammed Ali Chowdhury,1 Tao-Li Dai,1 Wei Han,1,3 1Department of Gastroenterology, Qilu Hospital of Shandong University, 2Department of Pathology, Medical School of Shandong University, 3Laboratory of Translational Gastroenterology, Shandong University, Qilu Hospital, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Introduction: The transient receptor potential ankyrin-1 (TRPA1 channel, a pain transducer and amplifier, is drawing increasing attention in the field of visceral hypersensitivity, commonly seen in irritable bowel syndrome and inflammatory bowel disease. However, the role of TRPA1 in visceral nociception during post-inflammatory states is not well defined. Here, we explore the correlation between TRPA1 expression in the spinal dorsal horn (SDH and persistent post-inflammatory visceral hypersensitivity.Methods: We injected rats intracolonically with 2,4,6-trinitrobenzene sulfonic acid (TNBS or vehicle (n=12 per group. Post-inflammatory visceral hypersensitivity was assessed by recording the electromyographic activity of the external oblique muscle in response to colorectal distension. TRPA1 expression and distribution in the spinal cord and colon were examined by Western blotting and immunohistochemistry.Results: Animals exposed to TNBS had more abdominal contractions than vehicle-injected controls (P<0.05, which corresponded to a lower nociceptive threshold. Expression of TRPA1 in the SDH (especially in the substantia gelatinosa and the colon was significantly greater in the TNBS-treated group than in controls (P<0.05. In the SDH, the number of TRPA1-immunopositive neurons was 25.75±5.12 in the control group and 34.25±7.89 in the TNBS-treated group (P=0.023, and integrated optical density values of TRPA1 in the control and TNBS-treated groups were 14,544.63±6,525.54 and 22,532.75±7,608.11, respectively (P=0.041.Conclusion: Our results indicate

  4. Selective retrograde transport of D-aspartate in spinal interneurons anc cortical neurons of rats

    International Nuclear Information System (INIS)

    Rustioni, A.; Cuenod, M.

    1982-01-01

    Retrograde labeling of neuronal elements in the brain and spinal cord has been investigated by autoradiographic techniques following injections of D-[ 3 H]aspartate (asp), [ 3 H]γ-aminobutyric acid (GABA) or horseradish peroxidase (HRP) in the medulla and spinal cord of rats. Twenty-four hours after D-[ 3 H]asp injections focused upon the cuneate nucleus, autoradiographic labeling is present over fibers in the pyramidal tract, internal capsule and over layer V pyramids in the forelimb representation of the sensorimotor cortex. After [ 3 H]GABA injections in the same nucleus no labeling attributable to retrograde translocation can be detected in spinal segments, brain stem or cortex. Conversely, injections of 30% HRP in the cuneate nucleus label neurons in several brain stem nuclei, in spinal gray and in layer V of the sensorimotor cortex. D-[ 3 H]Asp injections focused on the dorsal horn at cervical segments label a fraction of perikarya of the substantia gelatinosa and a sparser population of larger neurons in laminae IV to VI for a distance of 3-5 segments above and below the injection point. No brain stem neuronal perikarya appear labeled following spinal injections of D-[ 3 H]asp although autoradiographic grains overlie pyramidal tract fibers on the side contralateral to the injection. (Auth.)

  5. Tomografia de coerência óptica na distrofia corneana gelatinosa em gotas: relato de caso

    OpenAIRE

    Magalhães, Otávio de Azevedo; Rymer, Samuel; Marinho, Diane Ruschel; Kwitko, Sérgio; Cardoso, Isabel Habeyche; Kliemann, Lúcia

    2012-01-01

    Gelatinous drop-like corneal dystrophy is a rare disorder with few cases described in the present literature. The following report will show how difficult it is to diagnose this disease in early stages. Modern image exams, such as optical coherence tomography helps to diagnose and can be crucial to establish the best treatment. We will present the histopathological changes and clinical features in this unusual dystrophy.A distrofia corneana gelatinosa em gotas é uma desordem rara e pouco desc...

  6. Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.

    Science.gov (United States)

    Guttuso, T; Bergsland, N; Hagemeier, J; Lichter, D G; Pasternak, O; Zivadinov, R

    2018-02-01

    Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline ( P Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases ( P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known

  7. Dopamine-dependent neurotoxicity of lipopolysaccharide in substantia nigra.

    Science.gov (United States)

    De Pablos, Rocío M; Herrera, Antonio J; Villarán, Ruth F; Cano, Josefina; Machado, Alberto

    2005-03-01

    Intranigral injection of lipopolysaccharide (LPS), a potent inductor of inflammation, induces degeneration of dopaminergic neurons, along with an inflammatory process that features activation of microglial cells and loss of astrocytes. To test the involvement of dopamine (DA) in this degeneration induced by LPS, we treated albino Wistar rats with different concentrations of alpha-methyl-p-tyrosine (alpha-MPT), an inhibitor of tyrosine hydroxylase (TH) activity. Results showed that alpha-MPT prevented LPS-induced loss of TH immunostaining and expression of mRNA for TH and DA transporter; it also prevented substantial activation of microglial cells. Loss of the astroglial population, a marker of damage in our model, was also prevented. This protective effect resulted from inhibition of TH and the consequent decrease in DA concentration, because treatment with L-DOPA/benserazide, which bypasses TH inhibition induced by alpha-MPT, reversed the protective effect produced by this drug. These results point out the important contribution of DA to the vulnerability and degeneration of dopaminergic neurons of the substantia nigra. Knowledge about the involvement of DA in this process may lead to the possibility of new protection strategies against this important degenerative process.

  8. Adaptação de lente de contato gelatinosa especial para ceratocone Keratoconus special soft contact lens fitting

    Directory of Open Access Journals (Sweden)

    Ester Sakae Yamazaki

    2006-08-01

    Full Text Available OBJETIVO: Relatar a experiência inicial com o uso de lentes de contato gelatinosas especiais para ceratocone. MÉTODOS: Estudo retrospectivo de 80 olhos de 66 pacientes usuários de lentes de contato gelatinosas especial para ceratocone, no Setor de Lentes de Contato da UNIFESP e em clínicas particulares. Os pacientes foram classificados de acordo com o grau de gravidade da doença pela avaliação ceratométrica. Foram coletados os seguintes dados: idade, sexo, diagnóstico, ceratometria, acuidade visual com a lente, equivalente esférico (ES, curvatura da lente e indicação para o seu uso. RESULTADOS: Foram estudados 80 olhos de 66 pacientes usuários de lente gelatinosa para ceratocone. A média de idade foi de 29 anos, sendo 51,5% homens e 48,5% de mulheres. De acordo com os grupos: incipiente: 15,0%, moderado: 53,7%, avançado: 26,3%, grave: 5,0%. A maioria dos olhos estudados (91,25% apresentou acuidade visual melhor que 20/40 com a lente. Foram adaptadas 58% lentes de poder esférico (média de -5,45 dioptrias e 41% lentes com grau esferocilíndrico (variando de -0,50 a -5,00 dioptrias cilíndricas. A curva esférica mais utilizada foi de 7,6 mm (61% dos olhos. As principais razões para a escolha e adaptação desta lente foram devido à intolerância e ao padrão de adaptação insatisfatório com outras lentes. CONCLUSÃO: A lente gelatinosa para ceratocone pode ser usada em casos de difícil adaptação, como uma opção para melhorar o conforto e possibilitar a reabilitação visual em pacientes que não obtiveram alternativas a não ser algum procedimento cirúrgico.PURPOSE: To evaluate the fitting and use of a soft contact lens in keratoconic patients. METHODS: Retrospective study on 80 eyes of 66 patients, fitted with a special soft contact lens for keratoconus, at the Contact Lens Section of UNIFESP and private clinics. Keratoconus was classified according to degrees of disease severity by keratometric pattern. Age, gender

  9. Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra

    International Nuclear Information System (INIS)

    Dawson, T.M.; Dawson, V.L.; Gage, F.H.; Fisher, L.J.; Hunt, M.A.; Wamsley, J.K.

    1991-01-01

    Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative [3H]BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of [3H]SCH 23390-labeled D-1 receptors in the striatum (36.7%) and the substantia nigra (35.1%) and a 54.4% increase in the number (Bmax) of [3H]sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of [3H]BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat

  10. Neuronal and glial expression of inward rectifier potassium channel subunits Kir2.x in rat dorsal root ganglion and spinal cord.

    Science.gov (United States)

    Murata, Yuzo; Yasaka, Toshiharu; Takano, Makoto; Ishihara, Keiko

    2016-03-23

    Inward rectifier K(+) channels of the Kir2.x subfamily play important roles in controlling the neuronal excitability. Although their cellular localization in the brain has been extensively studied, only a few studies have examined their expression in the spinal cord and peripheral nervous system. In this study, immunohistochemical analyses of Kir2.1, Kir2.2, and Kir2.3 expression were performed in rat dorsal root ganglion (DRG) and spinal cord using bright-field and confocal microscopy. In DRG, most ganglionic neurons expressed Kir2.1, Kir2.2 and Kir2.3, whereas satellite glial cells chiefly expressed Kir2.3. In the spinal cord, Kir2.1, Kir2.2 and Kir2.3 were all expressed highly in the gray matter of dorsal and ventral horns and moderately in the white matter also. Within the gray matter, the expression was especially high in the substantia gelatinosa (lamina II). Confocal images obtained using markers for neuronal cells, NeuN, and astrocytes, Sox9, showed expression of all three Kir2 subunits in both neuronal somata and astrocytes in lamina I-III of the dorsal horn and the lateral spinal nucleus of the dorsolateral funiculus. Immunoreactive signals other than those in neuronal and glial somata were abundant in lamina I and II, which probably located mainly in nerve fibers or nerve terminals. Colocalization of Kir2.1 and 2.3 and that of Kir2.2 and 2.3 were present in neuronal and glial somata. In the ventral horn, motor neurons and interneurons were also immunoreactive with the three Kir2 subunits. Our study suggests that Kir2 channels composed of Kir2.1-2.3 subunits are expressed in neuronal and glial cells in the DRG and spinal cord, contributing to sensory transduction and motor control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Do Substantia Nigra Dopaminergic Neurons Differentiate Between Reward and Punishment?

    Institute of Scientific and Technical Information of China (English)

    Michael J. Frank; D. James Surmeier

    2009-01-01

    The activity of dopaminergic neurons are thought to be increased by stimuli that predict reward and decreased by stimuli that predict aversive outcomes. Recent work by Matsumoto and Hikosaka challenges this model by asserting that stimuli associated with either rewarding or aversive outcomes increase the activity of dopaminergic neurons in the substantia nigra pars compacta.

  12. Bidirectional modulation of substantia nigra activity by motivational state.

    Directory of Open Access Journals (Sweden)

    Mark A Rossi

    Full Text Available A major output nucleus of the basal ganglia is the substantia nigra pars reticulata, which sends GABAergic projections to brainstem and thalamic nuclei. The GABAergic (GABA neurons are reciprocally connected with nearby dopaminergic neurons, which project mainly to the basal ganglia, a set of subcortical nuclei critical for goal-directed behaviors. Here we examined the impact of motivational states on the activity of GABA neurons in the substantia nigra pars reticulata and the neighboring dopaminergic (DA neurons in the pars compacta. Both types of neurons show short-latency bursts to a cue predicting a food reward. As mice became sated by repeated consumption of food pellets, one class of neurons reduced cue-elicited firing, whereas another class of neurons progressively increased firing. Extinction or pre-feeding just before the test session dramatically reduced the phasic responses and their motivational modulation. These results suggest that signals related to the current motivational state bidirectionally modulate behavior and the magnitude of phasic response of both DA and GABA neurons in the substantia nigra.

  13. Bidirectional Modulation of Substantia Nigra Activity by Motivational State

    Science.gov (United States)

    Rossi, Mark A.; Fan, David; Barter, Joseph W.; Yin, Henry H.

    2013-01-01

    A major output nucleus of the basal ganglia is the substantia nigra pars reticulata, which sends GABAergic projections to brainstem and thalamic nuclei. The GABAergic (GABA) neurons are reciprocally connected with nearby dopaminergic neurons, which project mainly to the basal ganglia, a set of subcortical nuclei critical for goal-directed behaviors. Here we examined the impact of motivational states on the activity of GABA neurons in the substantia nigra pars reticulata and the neighboring dopaminergic (DA) neurons in the pars compacta. Both types of neurons show short-latency bursts to a cue predicting a food reward. As mice became sated by repeated consumption of food pellets, one class of neurons reduced cue-elicited firing, whereas another class of neurons progressively increased firing. Extinction or pre-feeding just before the test session dramatically reduced the phasic responses and their motivational modulation. These results suggest that signals related to the current motivational state bidirectionally modulate behavior and the magnitude of phasic response of both DA and GABA neurons in the substantia nigra. PMID:23936522

  14. Medindo o poder refrativo de lentes de contato gelatinosas personalizadas Measuring the refractive power of customized soft contact lenses

    Directory of Open Access Journals (Sweden)

    Luis Alberto Vieira de Carvalho

    2007-02-01

    Full Text Available OBJETIVO: Lentes de contato gelatinosas com curvas-base esféricas têm sido usadas há anos. O cálculo do poder refrativo de lentes deste tipo é fácil, bastando utilizarmos a equação do fabricante de lentes para lentes espessas. No entanto, para projetos de lentes de contato personalizadas, não há ainda métodos confiáveis para medida das aberrações ópticas de ordem mais alta. Esse trabalho foi desenvolvido no laboratório do Centro de Ciências da Visão (Center for Visual Science da Universidade de Rochester, Nova York, com aparelho óptico que permite realizar medidas precisas de aberrações de ordem baixa e alta de lentes de contato gelatinosas personalizadas. Este é um passo essencial na verificação e obtenção de lentes de contato personalizadas de qualidade, e o instrumento desenvolvido na Universidade de Rochester permite verificar a qualidade de fabricação destas lentes. MÉTODOS: Um aparelho óptico de bancada foi montado em laboratório. Este aparelho consiste de uma célula úmida onde as lentes de contato são depositadas. Consiste também de uma série de lentes e espelhos e um sensor de frente-de-onda de Hartmann-Shack. As lentes de contato personalizadas utilizadas neste projeto foram fabricadas pela empresa Bausch & Lomb. Das dezenas de lentes de contato mensuradas no aparelho, restringimos aqui a apresentar os resultados de uma lente personalizada para ceratocone. RESULTADOS: O erro quadrático médio (EQM do instrumento foi de 0,04 micrômetro, sendo que o EQM das aberrações induzidas na lente está entre 4 e 6 micrômetros, ou seja, a precisão do aparelho está em torno de 1%. Este valor é mais do que suficiente para medidas precisas destes tipos de lentes de contato, algo até então inviável utilizando-se os sensores ou aparelhos convencionais de aberrometria. CONCLUSÃO: Com o instrumento desenvolvido neste trabalho foi possível realizar medidas precisas de aberrações de alta ordem. Esta

  15. Determination of trace elements in the human substantia nigra

    Energy Technology Data Exchange (ETDEWEB)

    Morawski, M. [Paul-Flechsig-Institut fuer Hirnforschung, Universitaet Leipzig, Jahnallee 59, 04109 Leipzig (Germany)]. E-mail: morm@medizin.uni-leipzig.de; Meinecke, Ch. [Fakultaet fuer Physik und Geowissenschaften, Universitaet Leipzig, Linnestrasse 5, 04105 Leipzig (Germany); Reinert, T. [Fakultaet fuer Physik und Geowissenschaften, Universitaet Leipzig, Linnestrasse 5, 04105 Leipzig (Germany); Doerffel, A.C. [Paul-Flechsig-Institut fuer Hirnforschung, Universitaet Leipzig, Jahnallee 59, 04109 Leipzig (Germany); Riederer, P. [Klin. Neurochemie, Abt. Psychiatrie, Universitaet Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg (Germany); Arendt, T. [Paul-Flechsig-Institut fuer Hirnforschung, Universitaet Leipzig, Jahnallee 59, 04109 Leipzig (Germany); Butz, T. [Fakultaet fuer Physik und Geowissenschaften, Universitaet Leipzig, Linnestrasse 5, 04105 Leipzig (Germany)

    2005-04-01

    'The gain in brain is mainly in the stain' was long time a key sentence for research in neurodegenerative disease. However, for a quantification of the element concentrations (especially iron) in brain tissue, standard staining methods are insufficient. Advanced physical methods allow a quantitative elemental analysis of brain tissue. The sophisticated ion beam analysis provides a quantitative determination of elemental concentrations with a subcellular spatial resolution using a scanning proton beam focussed down to below 1 {mu}m that induces characteristic X-rays in the specimen (PIXE - particle induced X-ray emission). Histochemical and biochemical determinations of total iron content in brain regions from idiopathic Parkinson's disease have demonstrated an increase of iron in parkinsonian substantia nigra pars compacta but not in the pars reticulata, however without a clear cellular classification. For the first time, we have differentially investigated the intra- and extraneuronal elemental concentrations (especially iron) of the human substantia nigra pars compacta versus pars reticulata with detection limits in the range of 50 {mu}mol/l. Thus, we could compare the neuronal iron concentration in human brain sections of healthy and parkinsonian brain tissue. Clear differences in the iron concentration and distribution could be disclosed. Additionally, we could show in situ that the increased intraneuronal iron content is linked to neuromelanin.

  16. Proteome analysis of human substantia nigra in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Werner Cornelius J

    2008-02-01

    Full Text Available Abstract Background Parkinson's disease (PD is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra. Results The gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin and glutathione-related redox metabolism (GST M3, GST P1, GST O1, including novel redox proteins (SH3BGRL. Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin, as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation, aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism. Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results. Conclusion Using an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many

  17. Desempenho visual na correção de miopia com óculos e lentes de contato gelatinosas Visual performance in myopic correction with spectacles and soft contact lenses

    Directory of Open Access Journals (Sweden)

    Breno Barth

    2008-02-01

    Full Text Available OBJETIVOS: Avaliar o desempenho visual, por meio da acuidade visual LogMAR de alto contraste, sensibilidade ao contraste e análise de frentes de onda de indivíduos portadores de miopia com ou sem astigmatismo, corrigidos com óculos e com três diferentes lentes de contato gelatinosas [Acuvue® 2 (Vistacon J&J Vision Care Inc., EUA, Biomedics® 55 (Ocular Science, EUA e Focus® 1-2 week (Ciba Vision Corporation, EUA]. MÉTODOS: Estudo clínico e prospectivo com intervenção em amostra constituída por quarenta indivíduos portadores de miopia entre -1,00 D e -4,50 D, sem ou com astigmatismo até -0,75 D. RESULTADOS: A sobrerefração objetiva realizada pelo aberrômetro Zywave detectou diferença significativa entre as lentes de contato gelatinosas Acuvue® 2 e Biomedics® 55, em relação aos componentes refrativos esfera e equivalente esférico, que se mostraram hipercorrigidos em relação às lentes de contato gelatinosas Focus® 1-2 week. A acuidade visual LogMAR e sensibilidade ao contraste não detectaram diferenças no desempenho visual com os óculos e com as três lentes de contato gelatinosas. A análise de frentes de onda detectou diferença significativa na aberração de terceira ordem sem e com as lentes de contato gelatinosas, com melhor desempenho visual com as lentes de contato gelatinosas Acuvue® 2 e Biomedics® 55. CONCLUSÕES: A análise de frentes de onda detectou diferenças no desempenho visual com óculos e com as lentes de contato gelatinosas, sendo, portanto, uma medida mais sensível da função visual que a acuidade visual LogMAR de alto contraste e a sensibilidade ao contraste. O modelo de avaliação de desempenho visual com análise de frentes de onda utilizado nesta investigação serve de modelo para pesquisas semelhantes.PURPOSE: To evaluate the visual performance by high contrast visual acuity, contrast sensitivity and wavefront in myopic patients with or without astigmatism corrected with spectacles and

  18. Illicit stimulant use is associated with abnormal substantia nigra morphology in humans.

    Directory of Open Access Journals (Sweden)

    Gabrielle Todd

    Full Text Available Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is an increasing health problem. Chronic use can cause neurotoxicity in animals and humans but the long-term consequences are not well understood. The aim of the current study was to investigate the long-term effect of stimulant use on the morphology of the human substantia nigra. We hypothesised that history of illicit stimulant use is associated with an abnormally bright and enlarged substantia nigra (termed 'hyperechogenicity' when viewed with transcranial sonography. Substantia nigra morphology was assessed in abstinent stimulant users (n = 36; 31±9 yrs and in two groups of control subjects: non-drug users (n = 29; 24±5 yrs and cannabis users (n = 12; 25±7 yrs. Substantia nigra morphology was viewed with transcranial sonography and the area of echogenicity at the anatomical site of the substantia nigra was measured at its greatest extent. The area of substantia nigra echogenicity was significantly larger in the stimulant group (0.273±0.078 cm(2 than in the control (0.201±0.054 cm(2; P<0.001 and cannabis (0.202±0.045 cm(2; P<0.007 groups. 53% of stimulant users exhibited echogenicity that exceeded the 90(th percentile for the control group. The results of the current study suggest that individuals with a history of illicit stimulant use exhibit abnormal substantia nigra morphology. Substantia nigra hyperechogenicity is a strong risk factor for developing Parkinson's disease later in life and further research is required to determine if the observed abnormality in stimulant users is associated with a functional deficit of the nigro-striatal system.

  19. Assessment of substantia nigra echogenicity in German and Filipino populations using a portable ultrasound system.

    Science.gov (United States)

    Go, Criscely L; Frenzel, Antonia; Rosales, Raymond L; Lee, Lillian V; Benecke, Reiner; Dressler, Dirk; Walter, Uwe

    2012-02-01

    Transcranial sonography of the substantia nigra for diagnosing premotor stages of Parkinson disease has been attracting increasing interest. Standard reference values defining an abnormal increased echogenic size (hyperechogenicity) of the substantia nigra have been established in several populations using high-end stationary ultrasound systems. It is unknown whether a portable ultrasound system can be appropriately used and how the Filipino population would compare with the well-studied white population. We prospectively studied substantia nigra echogenic sizes and third ventricle widths in 71 healthy adult German participants and 30 age- and sex-matched Filipino participants using both a well-established stationary ultrasound system (in the German cohort) and a recently distributed portable ultrasound system (in both ethnic cohorts). Mean substantia nigra echogenic sizes, cutoff values defining abnormal hyperechogenicity, and intra-rater reliability were similar with both systems and in both ethnic cohorts studied. The Filipino and German participants did not differ with respect to the frequency of insufficient insonation conditions (each 3%) and substantia nigra hyperechogenicity (10% versus 9%; P = .80). However, third ventricle widths were smaller in the Filipino than the German participants (mean ± SD, 1.6 ± 1.1 versus 2.4 ± 1.0 mm; P = .004). The frequency of substantia nigra hyperechogenicity appears to be homogeneous in white and Asian populations. Screening for this feature may well be performed with a present-day portable ultrasound system.

  20. Substantia nigra depigmentation and exposure to encephalitis lethargica.

    Science.gov (United States)

    Hack, Nawaz; Jicha, Gregory A; Abell, Annalisa; Dean, Dawson; Vitek, Jerrold L; Berger, Joseph R

    2012-12-01

    Parkinsonism has occasionally been reported as a consequence of infectious diseases. The present study examines the clinical and pathological correlates of parkinsonism across birth cohorts in relation to critical exposure to the encephalitis lethargica epidemic in the early 1900s. The study population consisted of 678 participants in the Nun Study, of whom 432 died and came to autopsy. Qualitative indices of substantia nigra (SN) depigmentation were verified in a subset of 40 randomly selected subjects using quantitative stereological techniques. SN depigmentation, detected neuropathologically, was correlated with clinical parameters of Parkinson disease, age, and birth cohort. SN depigmentation was detected in 57 (13.2%) of the cohort. Although qualitative SN depigmentation correlated modestly with age (p = 0.02), it correlated best with birth cohort (p = 0.009) for women born in the years 1895-1899. Quantitative measures of SN depigmentation were increased in this birth cohort compared to age matched subjects from flanking birth cohorts 1890-1894 and 1900-1904 (p < 0.001). SN depigmentation correlated with speed of 6- and 50-foot walk (p < 0.0001), up and go test (p < 0.0001), and hand coordination (p < 0.0001). Subjects in the birth cohort 1895-1899 would have been in their late teens and 20s at the onset and during the peak of the encephalitis lethargica epidemic. These were precisely the age ranges of persons who were most often affected by the illness. These data suggest the possibility that the coexistence of parkinsonism and SN depigmentation in this birth cohort may have resulted from the yet undetermined infectious agent responsible for encephalitis lethargica. Copyright © 2012 American Neurological Association.

  1. Intrinsic and integrative properties of substantia nigra pars reticulata neurons

    Science.gov (United States)

    Zhou, Fu-Ming; Lee, Christian R.

    2011-01-01

    The GABA projection neurons of the substantia nigra pars reticulata (SNr) are output neurons for the basal ganglia and thus critical for movement control. Their most striking neurophysiological feature is sustained, spontaneous high frequency spike firing. A fundamental question is: what are the key ion channels supporting the remarkable firing capability in these neurons? Recent studies indicate that these neurons express tonically active TRPC3 channels that conduct a Na-dependent inward current even at hyperpolarized membrane potentials. When the membrane potential reaches −60 mV, a voltage-gated persistent sodium current (INaP) starts to activate, further depolarizing the membrane potential. At or slightly below −50 mV, the large transient voltage-activated sodium current (INaT) starts to activate and eventually triggers the rapid rising phase of action potentials. SNr GABA neurons have a higher density of (INaT), contributing to the faster rise and larger amplitude of action potentials, compared with the slow-spiking dopamine neurons. INaT also recovers from inactivation more quickly in SNr GABA neurons than in nigral dopamine neurons. In SNr GABA neurons, the rising phase of the action potential triggers the activation of high-threshold, inactivation-resistant Kv3-like channels that can rapidly repolarize the membrane. These intrinsic ion channels provide SNr GABA neurons with the ability to fire spontaneous and sustained high frequency spikes. Additionally, robust GABA inputs from direct pathway medium spiny neurons in the striatum and GABA neurons in the globus pallidus may inhibit and silence SNr GABA neurons, whereas glutamate synaptic input from the subthalamic nucleus may induce burst firing in SNr GABA neurons. Thus, afferent GABA and glutamate synaptic inputs sculpt the tonic high frequency firing of SNr GABA neurons and the consequent inhibition of their targets into an integrated motor control signal that is further fine-tuned by neuromodulators

  2. Assessment of cytochrome C oxidase dysfunction in the substantia nigra/ventral tegmental area in schizophrenia.

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    Matthew W Rice

    Full Text Available Perturbations in metabolism are a well-documented but complex facet of schizophrenia pathology. Optimal cellular performance requires the proper functioning of the electron transport chain, which is constituted by four enzymes located within the inner membrane of mitochondria. These enzymes create a proton gradient that is used to power the enzyme ATP synthase, producing ATP, which is crucial for the maintenance of cellular functioning. Anomalies in a single enzyme of the electron transport chain are sufficient to cause disruption of cellular metabolism. The last of these complexes is the cytochrome c oxidase (COX enzyme, which is composed of thirteen different subunits. COX is a major site for oxidative phosphorylation, and anomalies in this enzyme are one of the most frequent causes of mitochondrial pathology. The objective of the present report was to assess if metabolic anomalies linked to COX dysfunction may contribute to substantia nigra/ventral tegmental area (SN/VTA pathology in schizophrenia. We tested COX activity in postmortem SN/VTA from schizophrenia and non-psychiatric controls. We also tested the protein expression of key subunits for the assembly and activity of the enzyme, and the effect of antipsychotic medication on subunit expression. COX activity was not significantly different between schizophrenia and non-psychiatric controls. However, we found significant decreases in the expression of subunits II and IV-I of COX in schizophrenia. Interestingly, these decreases were observed in samples containing the entire rostro-caudal extent of the SN/VTA, while no significant differences were observed for samples containing only mid-caudal regions of the SN/VTA. Finally, rats chronically treated with antipsychotic drugs did not show significant changes in COX subunit expression. These findings suggest that COX subunit expression may be compromised in specific sub-regions of the SN/VTA (i.e. rostral regions, which may lead to a faulty

  3. Avaliação da qualidade óptica de lentes de contato gelatinosas na correção de miopia Evaluation of optical performance of soft contact lenses in myopic correction

    Directory of Open Access Journals (Sweden)

    Marcelo Weslley Dalcoll

    2008-12-01

    Full Text Available OBJETIVO: Avaliar a qualidade óptica de olhos adaptados com dois tipos diferentes de lentes de contato gelatinosas: Acuvue® 2 (Vistacon J&J Vision Care Inc., EUA e World Vision Disposable Asférica Wave Front® (World Vision Ophthalmic, Brasil. MÉTODOS: Estudo clínico e prospectivo com intervenção em amostra constituída por 40 indivíduos portadores de miopia entre -0,75D e -4,50D, sem ou com astigmatismo até -0,75D. Um olho de cada paciente foi sorteado para avaliação a qual incluiu acuidade visual de alto e baixo contraste, aberrometria e teste de sensibilidade ao contraste. RESULTADOS: A sobre-refração objetiva realizada pelo Nidek OPD-Scan detectou hipercorreção significativa para ambas as lentes de contato gelatinosas. A avaliação da AV logMAR de alto e baixo contraste mostrou diferença significativa favorável das lentes de contato gelatinosas em relação aos óculos e na comparação entre as lentes de contato gelatinosas, apenas em relação à AV logMAR de alto contraste, houve melhor desempenho da LC World Vision Disposable Asférica Wave Front® . A avaliação de sensibilidade ao contraste detectou melhor desempenho das lentes de contato gelatinosas em relação aos óculos para as freqüências espaciais de 1,5; 3; 6 e 18. Não houve diferença significativa entre os dois tipos de lentes de contato gelatinosas nas freqüências espaciais avaliadas. A análise de frentes de onda não identificou diferença significativa do índice de Strehl, função de transferência modular (MTF e das aberrações de alta ordem (aberrações totais, coma, trefoil, quadrifoil, esférica e astigmatismo secundário sem e com as lentes de contato gelatinosas, bem como na comparação entre elas. CONCLUSÃO: Houve melhor desempenho óptico da lente de contato gelatinosa World Vision Disposable Asférica Wave Front® na medida de AV logMAR de alto contraste. Não houve diferença entre as lentes de contato gelatinosas nas avalia

  4. [The role of the opiate mechanisms of the hippocampus and substantia nigra in the behavioral and convulsive disorders in picrotoxin-induced kindling].

    Science.gov (United States)

    Kryzhanovskiĭ, G N; Shandra, A A; Godlevskiĭ, L S; Mazarati, A M; Nguyen, T T

    1991-03-01

    It was shown in the experiments on rats that the repeated picrotoxin administration resulted in the kindling of generalized seizures. Generalized convulsions were followed by the development of either postictal depression or explosiveness. The injection of mu-opiate agonist met-enkephalin into hippocampus of kindled rats resulted in the increase in the severity of seizure reactions which were induced by picrotoxin and also in the increase in the number of animals with postictal explosiveness. The injection of dynorphin-A-1-13 (kappa-opiate agonist) into substantia nigra reticulata induced the locomotor depression which was like one in postictal period and resulted in the decrease of picrotoxin-induced seizures severity. It was concluded that mu-opiate system of hippocampus took part in the formation of generator of pathologically enhanced excitation in the structure during kindling and the development of seizure syndrome, providing also the postictal explosiveness. Kappa-opiate system of substantia nigra plays an important role in the activation of the antiepileptic system, limitation of seizures and the development of postictal depression.

  5. [Morphochemical changes in the substantia nigra cellular structures in Parkinson's disease].

    Science.gov (United States)

    Salkov, V N; Khudoerkov, R M; Voronkov, D N; Sobolev, V B; Kutukova, K A

    to clarify the features of morphochemical changes in the substantia nigra cellular structures in Parkinson's disease. The structural characteristics of the substantia nigra were studied microscopically and quantified using computer morphometric methods at brain autopsies of individuals with Parkinson's disease who had died from intercurrent diseases and those who had no evidence of neurological disorders in their history (a control group). This investigation could clarify the features of morphochemical changes in both the neural network structures and the glial populations of the substantia nigra in Parkinson's disease. The number of neurons containing tyrosine hydroxylase (a marker of dopamine neurons) in the compact part of the substantia nigra (a ventral region) was smaller and the density distribution of Lewy bodies was higher in the patients with Parkinson's disease than in the control group. The accumulation of iron (II) compounds in the cellular elements and neuropile and the increased expression of glial fibrillary acidic protein in Parkinson's disease were more pronounced than those in the controls. Postmortem diagnosis in Parkinson's disease should be based on a full description of a set of neuronal and glial morphochemical and structural changes in the substantia nigra rather than on the identification of cellular markers for the neurodegenerative process.

  6. Altered Tracer Distribution and Clearance in the Extracellular Space of the Substantia Nigra in a Rodent Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Yuan Fang

    2017-07-01

    Full Text Available The relationship between extracellular space (ECS diffusion parameters and brain drug clearance is not well-studied, especially in the context of Parkinson's disease (PD. Therefore, we used a rodent model of PD to explore the distribution and clearance of a magnetic resonance tracer. Forty male Sprague Dawley rats were randomized into four different groups: a PD group, a Madopar group (PD + Madopar treatment, a sham group, and a control group. All rats received an injection of the extracellular tracer gadolinium-diethylene triaminepentacetic acid (Gd-DTPA directly into the substantia nigra (SN. ECS diffusion parameters including the effective diffusion coefficient (D*, clearance coefficient (k', ratio of the maximum distribution volume of the tracer (Vd-max%, and half-life (t1/2 were measured. We found that all parameters were significantly increased in the PD group compared to the other three groups (D*: F = 5.774, p = 0.0025; k': F = 20.00, P < 0.0001; Vd-max%: F = 12.81, P < 0.0001; and t1/2: F = 23.35, P < 0.0001. In conclusion, the PD group exhibited a wider distribution and lower clearance of the tracer compared to the other groups. Moreover, k' was more sensitive than D* for monitoring morphological and functional changes in the ECS in a rodent model of PD.

  7. Ventral Tegmental Area and Substantia Nigra Neural Correlates of Spatial Learning

    Science.gov (United States)

    Martig, Adria K.; Mizumori, Sheri J. Y.

    2011-01-01

    The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) may provide modulatory signals that, respectively, influence hippocampal (HPC)- and striatal-dependent memory. Electrophysiological studies investigating neural correlates of learning and memory of dopamine (DA) neurons during classical conditioning tasks have found DA…

  8. Substantia nigra in MR images in Parkinson disease and MPTP exposure

    International Nuclear Information System (INIS)

    De La Paz, R.L.; Duguid, J.; Langston, W.J.

    1986-01-01

    Eight patients, aged 60-77 years, with idiopathic Parkinson disease were studied to determine whether the characteristic degeneration of the substantia nigra (zona compacta), seen pathologically, could be identified in vivo on T2-weighted proton MR imaging (1.5 T). The mean width of the substantia nigra in the eight patients was 4.1 mm (SEM = 0.21 mm), significantly (rho < .004) less than the mean width of 5.2 mm (SEM= 0.30 mm) in ten age-matched controls. Overlap with control values was seen in only one patient. No clear correlation between low signal in the putamen (suggesting excess deposition of iron, Fe/sup 3+/) and Parkinson disease was seen. Narrowing of the substantia nigra on MR imaging was also seen in one patient with drug-induced Parkinson syndrome (MPTP exposure). These changes on MR imaging are probably due to atrophy of the zona compacta of the substantia nigra, but excess iron in the zona reticulata may partially contribute to these findings. MR imaging may be useful for differentiating ''classic'' Parkinson disease from other extrapyramidal degenerative disorders and for predicting response to drug therapy

  9. Neurosteroid biosynthetic pathway changes in substantia nigra and caudate nucleus in Parkinson's disease

    NARCIS (Netherlands)

    Luchetti, Sabina; Bossers, Koen; Frajese, Giovanni Vanni; Swaab, Dick F.

    2010-01-01

    There is emerging evidence from animal studies for a neuroprotective role of sex steroids in neurodegenerative diseases, but studies in human brain are lacking. We have carried out an extensive study of the neurosteroid biosynthetic pathways in substantia nigra (SN), caudate nucleus (CN) and putamen

  10. Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson’s Disease

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    Kyle Farmer

    2015-08-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA, or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0 and LPC (18:1, which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD.

  11. Seizure-induced damage to substantia nigra and globus pallidus is accompanied by pronounced intra- and extracellular acidosis

    International Nuclear Information System (INIS)

    Inamura, K.; Smith, M.L.; Hansen, A.J.; Siesjoe, B.K.

    1989-01-01

    Status epilepticus of greater than 30-min duration in rats gives rise to a conspicuous lesion in the substantia nigra pars reticulata (SNPR) and globus pallidus (GP). The objective of the present study was to explore whether the lesion, which encompasses necrosis of both neurons and glial cells, is related to intra- and extracellular acidosis. Using the flurothyl model previously described to produce seizures, we assessed regional pH values with the autoradiographic 5,5-dimethyl[2-14C]oxazolidine-2,4-dione technique. Regional pH values were assessed in animals with continuous seizures for 20 and 60 min, as well as in those allowed to recover for 30 and 120 min after seizure periods of 20 or 60 min. In additional animals, changes in extracellular fluid pH (pHe) were measured with ion-selective microelectrodes, and extracellular fluid (ECF) volume was calculated from the diffusion profile for electrophoretically administered tetramethylammonium. In structures such as the neocortex and the hippocampus, which show intense metabolic activation during seizures, status epilepticus of 20- and 60-min duration was accompanied by a reduction of the composite tissue pH (pHt) of 0.2-0.3 unit. Recovery of pHt was observed upon termination of seizures. In SNPR and in GP, the acidosis was marked to excessive after 20 and 60 min of seizures (delta pHt approximately 0.6 after 60 min)

  12. Electrophysiological localization of distinct calcium potentials at selective somatodendritic sites in the substantia nigra

    DEFF Research Database (Denmark)

    Hounsgaard, J; Nedergaard, S; Greenfield, S A

    1992-01-01

    of differential polarization through applied electric fields, the cell body and dendrites have been activated in effective isolation during intracellular recordings from pars compacta neurons in the substantia nigra in vitro. In one class of neurons, which discharge in a "phasic" fashion and are located......The dendrites of dopaminergic neurons in the substantia nigra play a pivotal role in the neurochemical homeostasis of the nucleus. It is conceivable therefore that the cell body and dendrites of these nigral neurons possess distinct and independent electro-responsive features. By means......, a high-threshold calcium spike is located principally in the cell body. The differential localization of these calcium conductances in sub-populations of neurons is likely to determine the functions for the calcium responses in each type of neuron, and moreover highlight the dendrites as dynamic...

  13. 9.4 T MR microscopy of the substantia nigra with pathological validation in controls and disease

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    LA Massey

    2017-01-01

    Conclusions: We present a histologically validated anatomical description of the substantia nigra on high field spin-echo high resolution magnetic resonance images and were able to delineate all five nigrosomes. In accordance with the pathological literature we did not observe changes in the nigrosome structure as manifest by volume or signal characteristics within the substantia nigra in Parkinson's disease whereas in progressive supranuclear palsy there was microarchitectural destruction.

  14. Supersensitivity of GABAergic systems induced within rat substantia nigra and globus pallidus by haloperidol

    International Nuclear Information System (INIS)

    Frey, J.J.M.

    1986-01-01

    The supersensitivity was demonstrated by an increase in the responsiveness of individual neurons within these brain regions to microiontophoretically-applied GABA and by an up regulation of GABA binding sites. Rates received haloperidol for 30 days in their feed and were then withdrawn from treatment for 48 hrs. 3 H-GABA binding was found to be significantly elevated with the SN R (55%) and GP (42%). Scatchard analysis of 3 H-muscimol binding isotherms indicated that the number (B max ) of high affinity binding sites within the GP was significantly increased (32%); within the SN R , significant increases were detected in the B max of both high (23%) and low (58%) affinity 3 H-muscimol binding sites. After CHAL treatment, signs of dopaminergic supersensitivity within the basal ganglia were also observed. Spontaneous locomotor activity and apomorphine-induced stereotyped behavior were increased and specific 3 H-spiroperidol binding was elevated within the striatum (60%) and GP (236%)

  15. The Hyperpolarization-Activated Current Determines Synaptic Excitability, Calcium Activity and Specific Viability of Substantia Nigra Dopaminergic Neurons

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    Carmen Carbone

    2017-06-01

    Full Text Available Differential vulnerability between Substantia Nigra pars compacta (SNpc and Ventral Tegmental Area (VTA dopaminergic (DAergic neurons is a hallmark of Parkinson’s disease (PD. Understanding the molecular bases of this key histopathological aspect would foster the development of much-needed disease-modifying therapies. Non-heterogeneous DAergic degeneration is present in both toxin-based and genetic animal models, suggesting that cellular specificity, rather than causing factors, constitutes the background for differential vulnerability. In this regard, we previously demonstrated that MPP+, a neurotoxin able to cause selective nigrostriatal degeneration in animal rodents and primates, inhibits the Hyperpolarization-activated current (Ih in SNpc DAergic neurons and that pharmacological Ih antagonism causes potentiation of evoked Excitatory post-synaptic potentials (EPSPs. Of note, the magnitude of such potentiation is greater in the SNpc subfield, consistent with higher Ih density. In the present work, we show that Ih block-induced synaptic potentiation leads to the amplification of somatic calcium responses (SCRs in vitro. This effect is specific for the SNpc subfield and largely mediated by L-Type calcium channels, as indicated by sensitivity to the CaV 1 blocker isradipine. Furthermore, Ih is downregulated by low intracellular ATP and determines the efficacy of GABAergic inhibition in SNpc DAergic neurons. Finally, we show that stereotaxic administration of Ih blockers causes SNpc-specific neurodegeneration and hemiparkinsonian motor phenotype in rats. During PD progression, Ih downregulation may result from mitochondrial dysfunction and, in concert with PD-related disinhibition of excitatory inputs, determine a SNpc-specific disease pathway.

  16. Near-Infrared Confocal Laser Reflectance Cytoarchitectural Imaging of the Substantia Nigra and Cerebellum in the Fresh Human Cadaver.

    Science.gov (United States)

    Cheyuo, Cletus; Grand, Walter; Balos, Lucia L

    2017-01-01

    Cytoarchitectural neuroimaging remains critical for diagnosis of many brain diseases. Fluorescent dye-enhanced, near-infrared confocal in situ cellular imaging of the brain has been reported. However, impermeability of the blood-brain barrier to most fluorescent dyes limits clinical utility of this modality. The differential degree of reflectance from brain tissue with unenhanced near-infrared imaging may represent an alternative technique for in situ cytoarchitectural neuroimaging. We assessed the utility of unenhanced near-infrared confocal laser reflectance imaging of the cytoarchitecture of the cerebellum and substantia nigra in 2 fresh human cadaver brains using a confocal near-infrared laser probe. Cellular images based on near-infrared differential reflectance were captured at depths of 20-180 μm from the brain surface. Parts of the cerebellum and substantia nigra imaged using the probe were subsequently excised and stained with hematoxylin and eosin for histologic correlation. Near-infrared reflectance imaging revealed the 3-layered cytoarchitecture of the cerebellum, with Purkinje cells appearing hyperreflectant. In the substantia nigra, neurons appeared hyporeflectant with hyperreflectant neuromelanin cytoplasmic inclusions. Cytoarchitecture of the cerebellum and substantia nigra revealed on near-infrared imaging closely correlated with the histology on hematoxylin-eosin staining. We showed that unenhanced near-infrared reflectance imaging of fresh human cadaver brain can reliably identify and distinguish neurons and detailed cytoarchitecture of the cerebellum and substantia nigra. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra.

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    Alison L McCormack

    Full Text Available The protein alpha-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal alpha-synuclein burden. Here, feasibility and safety of alpha-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA directed against alpha-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of alpha-synuclein mRNA and protein in the infused (left vs. untreated (right hemisphere and revealed a significant 40-50% suppression of alpha-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in alpha-synuclein. Infusion with alpha-synuclein siRNA, while lowering alpha-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i the number and phenotype of nigral dopaminergic neurons, and (ii the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-alpha-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics.

  18. Optical coherence tomography image in gelatinous drop-like corneal dystrophy: case report Tomografia de coerência óptica na distrofia corneana gelatinosa em gotas: relato de caso

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    Otávio de Azevedo Magalhães

    2012-10-01

    Full Text Available Gelatinous drop-like corneal dystrophy is a rare disorder with few cases described in the present literature. The following report will show how difficult it is to diagnose this disease in early stages. Modern image exams, such as optical coherence tomography helps to diagnose and can be crucial to establish the best treatment. We will present the histopathological changes and clinical features in this unusual dystrophy.A distrofia corneana gelatinosa em gotas é uma desordem rara e pouco descrita em nossa literatura. O caso apresentado demonstra a dificuldade de realizar o diagnóstico nas fases mais iniciais da doença. O uso de modernos exames de imagem, como a tomografia de coerência óptica de segmento anterior, auxilia no diagnóstico e pode ser crucial para definir a melhor conduta terapêutica. Apresentaremos as alterações histopatológicas e as características clínicas desta incomum distrofia.

  19. Complement activation in the Parkinson's disease substantia nigra: an immunocytochemical study

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    Conant Stephanie B

    2006-10-01

    Full Text Available Abstract Background Inflammatory processes are increased in the Parkinson's disease (PD brain. The long-term use of nonsteroidal anti-inflammatory drugs has been associated, in retrospective studies, with decreased risk for PD, suggesting that inflammation may contribute to development of this disorder. The objective of this study was to determine the extent of complement activation, a major inflammatory mechanism, in PD. Methods Substantia nigra specimens from young normal subjects (n = 11–13, aged normal subjects (n = 24–28, and subjects with PD (n = 19–20, Alzheimer's disease (AD; n = 12–13, and dementia with Lewy bodies (DLB; n = 9 were stained for iC3b and C9, representing early- and late-stage complement activation, respectively. Numbers of iC3b+, C9+, and total melanized neurons in each section were counted in a blinded fashion. Nonparametric analyses were used to evaluate differences between groups and to evaluate correlations between complement staining, numbers of melanized neurons, and the duration of PD. Results Lewy bodies in both PD and DLB specimens stained for iC3b and C9. Staining was also prominent on melanized neurons. The percentage of iC3b+ neurons was significantly increased in PD vs. aged normal and AD specimens, and in young normal vs. aged normal specimens. C9 immunoreactivity was significantly increased in PD vs. AD specimens, but unlike iC3b, the increased C9 staining in PD and young normal specimens did not achieve statistical significance vs. aged normal specimens. iC3b and C9 staining in PD specimens was not correlated with the numbers of remaining melanized neurons, nor with the duration of PD. Conclusion Complement activation occurs on Lewy bodies and melanized neurons in the PD substantia nigra. Early complement activation (iC3b is increased on melanized neurons in PD vs. aged normal specimens, and late-stage complement activation (C9 also tends to increase. This latter finding suggests that complement

  20. Three-dimensional magnetic resonance spectroscopic imaging in the substantia nigra of healthy controls and patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Groeger, Adriane; Godau, Jana; Berg, Daniela; Chadzynski, Grzegorz; Klose, Uwe

    2011-01-01

    To investigate the substantia nigra in patients with Parkinson's disease three-dimensional magnetic resonance spectroscopic imaging with high spatial resolution at 3 Tesla was performed. Regional variations of spectroscopic data between the rostral and caudal regions of the substantia nigra as well as the midbrain tegmentum areas were evaluated in healthy controls and patients with Parkinson's disease. Nine patients with Parkinson's disease and eight age- and gender-matched healthy controls were included in this study. Data were acquired by using three-dimensional magnetic resonance spectroscopic imaging measurements. The ratios between rostral and caudal voxels of the substantia nigra as well as the midbrain tegmentum areas were calculated for the main-metabolites N-acetyl aspartate, creatine, choline, and myo-inositol. Additionally, the metabolite/creatine ratios were calculated. In all subjects spectra of acceptable quality could be obtained with a nominal voxel size of 0.252 ml. The calculated rostral-to-caudal ratios of the metabolites as well as of the metabolite/creatine ratios showed with exception of choline/creatine ratio significant differences between healthy controls and patients with Parkinson's disease. The findings from this study indicate that regional variations in N-acetyl aspartate/creatine ratios in the regions of the substantia nigra may differentiate patients with Parkinson's disease and healthy controls. (orig.)

  1. PADRONIZAÇÃO DE EXCIPIENTES PARA MANIPULAÇÃO DE CÁPSULAS GELATINOSAS DURAS CONTENDO EXTRATO SECO DE VALERIANA (Valeriana officinalis, PRODUZIDAS NO PROJETO FARMÁCIA VIVA EM SOBRAL-CE

    Directory of Open Access Journals (Sweden)

    Antônio Neudimar Bastos Costa

    2016-07-01

    Full Text Available O Projeto Farmácia Viva é o primeiro projeto de assistência social farmacêutica desenvolvido no Brasil baseado no emprego científico de plantas medicinais. Dentre as formulações padronizadas a partir de cápsulas gelatinosas duras, destacam-se as cápsulas contendo Extrato Seco de Valeriana. Para manipulação dessas cápsulas, é necessária uma quantidade adicional de excipientes, que possuem papel importante na qualidade, segurança e no desempenho do medicamento. O objetivo deste estudo é padronizar excipientes para formulação fitoterápica em cápsulas manipuladas no Projeto Farmácia Viva. A metodologia seguida foi por meio de análise bibliográfica sobre os variados excipientes e fitoterápicos e análise de bulas de medicamentos para posterior sugestão de padronização. Foram manipuladas 30 cápsulas e submetidas ao controle da qualidade, onde foram avaliados o peso médio, limite de variação, coeficiente de variação, desvio padrão e variação do conteúdo teórico das cápsulas. A formulação de Valeriana proposta teve como excipientes escolhidos o estearato de magnésio (0,5 % como lubrificante, o dióxido de silício coloidal (1,0 % como deslizante, o talco farmacêutico (1,0 % como adsorvente, o amido farmacêutico (73,0 % como um diluente hidrofóbico, lactose monohidratada (24,5 % como um diluente hidrofílico. Todos os resultados do controle da qualidade obtidos atenderam as especificações farmacopeicas.

  2. Age-related decreases in the concentration of Met- and Leu-enkephalin and neurotensin in the basal ganglia or rats

    International Nuclear Information System (INIS)

    Ceballos, M.L. de; Boyce, S.; Taylor, M.; Jenner, P.; Marsden, C.D.

    1987-01-01

    Previous studies using radioimmunoassay procedures have failed to show age-related changes in the concentration of Met-and Leu-enkephalin or neurotensin in rat basal ganglia. In contrast, using a combined high-pressure liquid chromatography (HLPC)- radioimmunoassay (RIA) technique we now report considerable decreases in the levels of these neuropeptides in areas of basal ganglia of 22 months-old compared to 3 months-old male Wistar rats. The concentration of Met-enkephalin was greatly reduced in the striatum and nucleus accumbens, but not in substantia nigra, of old compared to young animals. There was a similarly large decrease in Leu-enkephalin content in striatum of old rats with less marked decreases occurring in both the nucleus accumbens and substantia nigra. Neurotensin levels in the striatum and substantia nigra were greatly reduced in old rats, with a less marked decrease in the nucleus accumbens

  3. Age-related decreases in the concentration of Met- and Leu-enkephalin and neurotensin in the basal ganglia or rats

    Energy Technology Data Exchange (ETDEWEB)

    Ceballos, M.L. de; Boyce, S; Taylor, M; Jenner, P; Marsden, C D

    1987-03-20

    Previous studies using radioimmunoassay procedures have failed to show age-related changes in the concentration of Met-and Leu-enkephalin or neurotensin in rat basal ganglia. In contrast, using a combined high-pressure liquid chromatography (HLPC)- radioimmunoassay (RIA) technique we now report considerable decreases in the levels of these neuropeptides in areas of basal ganglia of 22 months-old compared to 3 months-old male Wistar rats. The concentration of Met-enkephalin was greatly reduced in the striatum and nucleus accumbens, but not in substantia nigra, of old compared to young animals. There was a similarly large decrease in Leu-enkephalin content in striatum of old rats with less marked decreases occurring in both the nucleus accumbens and substantia nigra. Neurotensin levels in the striatum and substantia nigra were greatly reduced in old rats, with a less marked decrease in the nucleus accumbens.

  4. MRI in Parkinson's disease and vascular Parkinsonism; Study on the lesion of substantia nigra

    Energy Technology Data Exchange (ETDEWEB)

    Aotsuka, Akiyo; Shinotoh, Hitoshi; Hirayama, Keizo [Chiba Univ. (Japan). School of Medicine; Ikehira, Hiroo; Fukuda, Hiroshi

    1991-06-01

    We examined the magnetic resonance (MR) image of midbrain and striatum in 30 patients with Parkinson's disease (PD), 10 patients with vascular Parkinsonism (VP) and 10 age-matched control subjects. Studies were performed on a high field strength (1.5 tesla) MRI unit. T2-weighted spin echo pulse sequence (TR 2500 ms/TE 40 ms) was used. Intensity profiles of a straight line perpendicular to the pars compacta through the center of the red nucleus were made on an image of the midbrain. We measured the width of the valley at half-height between the peaks of intensity representing the red nucleus and the crus cerebri-pars reticulata complex and used this as an index of the width of the pars compacta signal. The mean width of the pars compacta signal was 2.7 mm in the PD group and 4.3 mm in controls. The difference between the means was highly significant (p<0.01). While not significant statistically, there was a trend toward narrowing of the width of pars compacta signal of substantia nigra in the PD group as the Yahr's grade or disease duration progressed. In hemiparkinsonism, MRI revealed significant narrowing of the pars compacta signal on the contra-lateral side to the clinical predominant side. The mean width of the pars compacta signal was 3.9 mm in the VP group, but the decrease was not significant. MRI in VP group showed multiple high intensity area in the basal ganglia and the white matter, and periventricular hyperintensity area (PVHIA). There was no statistically significant difference in the frequency of restoration of the signal intensity in the lateral portion of the substantia nigra among PD, VP and control groups. The low signal intensity in the posterolateral putamen was not found in the 3 groups. The narrowing of the pars compacta signal has been attributed either to atrophy of the pars compacta or to increased deposition of iron in this region. The narrowing of the pars compacta signal reflected pathophysiology of PD. (J.P.N.).

  5. Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict Success of Declarative Memory Formation.

    Science.gov (United States)

    Kamiński, Jan; Mamelak, Adam N; Birch, Kurtis; Mosher, Clayton P; Tagliati, Michele; Rutishauser, Ueli

    2018-04-12

    The encoding of information into long-term declarative memory is facilitated by dopamine. This process depends on hippocampal novelty signals, but it remains unknown how midbrain dopaminergic neurons are modulated by declarative-memory-based information. We recorded individual substantia nigra (SN) neurons and cortical field potentials in human patients performing a recognition memory task. We found that 25% of SN neurons were modulated by stimulus novelty. Extracellular waveform shape and anatomical location indicated that these memory-selective neurons were putatively dopaminergic. The responses of memory-selective neurons appeared 527 ms after stimulus onset, changed after a single trial, and were indicative of recognition accuracy. SN neurons phase locked to frontal cortical theta-frequency oscillations, and the extent of this coordination predicted successful memory formation. These data reveal that dopaminergic neurons in the human SN are modulated by memory signals and demonstrate a progression of information flow in the hippocampal-basal ganglia-frontal cortex loop for memory encoding. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output.

    Science.gov (United States)

    Brown, Jennifer; Pan, Wei-Xing; Dudman, Joshua Tate

    2014-05-21

    Dysfunction of the basal ganglia produces severe deficits in the timing, initiation, and vigor of movement. These diverse impairments suggest a control system gone awry. In engineered systems, feedback is critical for control. By contrast, models of the basal ganglia highlight feedforward circuitry and ignore intrinsic feedback circuits. In this study, we show that feedback via axon collaterals of substantia nigra projection neurons control the gain of the basal ganglia output. Through a combination of physiology, optogenetics, anatomy, and circuit mapping, we elaborate a general circuit mechanism for gain control in a microcircuit lacking interneurons. Our data suggest that diverse tonic firing rates, weak unitary connections and a spatially diffuse collateral circuit with distinct topography and kinetics from feedforward input is sufficient to implement divisive feedback inhibition. The importance of feedback for engineered systems implies that the intranigral microcircuit, despite its absence from canonical models, could be essential to basal ganglia function. DOI: http://dx.doi.org/10.7554/eLife.02397.001. Copyright © 2014, Brown et al.

  7. Neurite orientation dispersion and density imaging in the substantia nigra in idiopathic Parkinson disease

    International Nuclear Information System (INIS)

    Kamagata, Koji; Suzuki, Michimasa; Hori, Masaaki; Kumamaru, Kanako K.; Aoki, Shigeki; Hatano, Taku; Okuzumi, Ayami; Motoi, Yumiko; Hattori, Nobutaka; Abe, Osamu; Shimoji, Keigo; Kamiya, Kouhei

    2016-01-01

    We used neurite orientation dispersion and density imaging (NODDI) to quantify changes in the substantia nigra pars compacta (SNpc) and striatum in Parkinson disease (PD). Diffusion-weighted magnetic resonance images were acquired from 58 PD patients and 36 age- and sex-matched controls. The intracellular volume fraction (Vic), orientation dispersion index (OD), and isotropic volume fraction (Viso) of the basal ganglia were compared between groups. Multivariate logistic regression analysis determined which diffusion parameters were independent predictors of PD. Receiver operating characteristic (ROC) analysis compared the diagnostic accuracies of the evaluated indices. Pearson coefficient analysis correlated each diffusional parameter with disease severity. Vic in the contralateral SNpc and putamen were significantly lower in PD patients than in healthy controls (P < 0.00058). Vic and OD in the SNpc and putamen showed significant negative correlations (P < 0.05) with disease severity. Multivariate logistic analysis revealed that Vic (P = 0.0000046) and mean diffusivity (P = 0.019) in the contralateral SNpc were the independent predictors of PD. In the ROC analysis, Vic in the contralateral SNpc showed the best diagnostic performance (mean cutoff, 0.62; sensitivity, 0.88; specificity, 0.83). NODDI is likely to be useful for diagnosing PD and assessing its progression. (orig.)

  8. Neurite orientation dispersion and density imaging in the substantia nigra in idiopathic Parkinson disease.

    Science.gov (United States)

    Kamagata, Koji; Hatano, Taku; Okuzumi, Ayami; Motoi, Yumiko; Abe, Osamu; Shimoji, Keigo; Kamiya, Kouhei; Suzuki, Michimasa; Hori, Masaaki; Kumamaru, Kanako K; Hattori, Nobutaka; Aoki, Shigeki

    2016-08-01

    We used neurite orientation dispersion and density imaging (NODDI) to quantify changes in the substantia nigra pars compacta (SNpc) and striatum in Parkinson disease (PD). Diffusion-weighted magnetic resonance images were acquired from 58 PD patients and 36 age- and sex-matched controls. The intracellular volume fraction (Vic), orientation dispersion index (OD), and isotropic volume fraction (Viso) of the basal ganglia were compared between groups. Multivariate logistic regression analysis determined which diffusion parameters were independent predictors of PD. Receiver operating characteristic (ROC) analysis compared the diagnostic accuracies of the evaluated indices. Pearson coefficient analysis correlated each diffusional parameter with disease severity. Vic in the contralateral SNpc and putamen were significantly lower in PD patients than in healthy controls (P disease severity. Multivariate logistic analysis revealed that Vic (P = 0.0000046) and mean diffusivity (P = 0.019) in the contralateral SNpc were the independent predictors of PD. In the ROC analysis, Vic in the contralateral SNpc showed the best diagnostic performance (mean cutoff, 0.62; sensitivity, 0.88; specificity, 0.83). NODDI is likely to be useful for diagnosing PD and assessing its progression. • Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique • NODDI estimates neurite microstructure more specifically than diffusion tensor imaging • By using NODDI, nigrostriatal alterations in PD can be evaluated in vivo • NOODI is useful for diagnosing PD and assessing its disease progression.

  9. Substantia nigra hyperechogenicity is related to decline in verbal memory in healthy elderly adults.

    Science.gov (United States)

    Yilmaz, R; Behnke, S; Liepelt-Scarfone, I; Roeben, B; Pausch, C; Runkel, A; Heinzel, S; Niebler, R; Suenkel, U; Eschweiler, G W; Maetzler, W; Berg, D

    2016-05-01

    Deficits in cognition have been reported in Parkinson's disease (PD) already in the early and even in the pre-motor stages. Whilst substantia nigra hyperechogenicity measured by transcranial B-mode sonography (TCS) represents a strong PD marker and is associated with an increased risk for PD in still healthy individuals, its association with cognitive performance in prodromal PD stages is not well established. Two different cohorts of healthy elderly individuals were assessed by TCS and two different neuropsychological test batteries covering executive functions, verbal memory, language, visuo-constructional function and attention. Cognitive performance was compared between individuals with hyperechogenicity (SN+) and without hyperechogenicity (SN-). In both cohorts, SN+ individuals performed significantly worse than the SN- group in tests assessing verbal memory (word list delayed recall P = 0.05, logical memory II P Color-Word Reading, P = 0.004) could only be shown in one of the two cohorts. No between-group effects were found in other cognitive tests and domains. These results indicate that individuals with the PD risk marker SN+ perform worse in verbal memory compared to SN- independent of the assessment battery. Memory performance should be assessed in detail in individuals at risk for PD. © 2016 EAN.

  10. Controlling absence seizures by deep brain stimulus applied on substantia nigra pars reticulata and cortex

    International Nuclear Information System (INIS)

    Hu, Bing; Wang, Qingyun

    2015-01-01

    Epilepsy is a typical neural disease in nervous system, and the control of seizures is very important for treating the epilepsy. It is well known that the drug treatment is the main strategy for controlling the epilepsy. However, there are about 10–15 percent of patients, whose seizures cannot be effectively controlled by means of the drug. Alternatively, the deep brain stimulus (DBS) technology is a feasible method to control the serious seizures. However, theoretical explorations of DBS are still absent, and need to be further made. Presently, we will explore to control the absence seizures by introducing the DBS to a basal ganglia thalamocortical network model. In particular, we apply DBS onto substantia nigra pars reticulata (SNr) and the cortex to explore its effects on controlling absence seizures, respectively. We can find that the absence seizure can be well controlled within suitable parameter ranges by tuning the period and duration of current stimulation as DBS is implemented in the SNr. And also, as the DBS is applied onto the cortex, it is shown that for the ranges of present parameters, only adjusting the duration of current stimulation is an effective control method for the absence seizures. The obtained results can have better understanding for the mechanism of DBS in the medical treatment.

  11. Direct monitoring of dopamine and 5-HT release in substantia nigra and ventral tegmental area in vitro

    DEFF Research Database (Denmark)

    Rice, M E; Richards, C D; Nedergaard, S

    1994-01-01

    Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous...... these regions with in situ electrodes and demonstrates the utility of fast-scan cyclic voltammetry to investigate the mechanisms and possible non-classical functions of somato-dendritic DA release....

  12. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  13. Molecular and functional differences in voltage-activated sodium currents between GABA projection neurons and dopamine neurons in the substantia nigra

    OpenAIRE

    Ding, Shengyuan; Wei, Wei; Zhou, Fu-Ming

    2011-01-01

    GABA projection neurons (GABA neurons) in the substantia nigra pars reticulata (SNr) and dopamine projection neurons (DA neurons) in substantia nigra pars compacta (SNc) have strikingly different firing properties. SNc DA neurons fire low-frequency, long-duration spikes, whereas SNr GABA neurons fire high-frequency, short-duration spikes. Since voltage-activated sodium (NaV) channels are critical to spike generation, the different firing properties raise the possibility that, compared with DA...

  14. The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra.

    Directory of Open Access Journals (Sweden)

    Margaret I Davis

    Full Text Available Presynaptic cannabinoid-1 receptors (CB1-R bind endogenous and exogenous cannabinoids to modulate neurotransmitter release. CB1-Rs are expressed throughout the basal ganglia, including striatum and substantia nigra, where they play a role in learning and control of motivated actions. However, the pattern of CB1-R expression across different striatal compartments, microcircuits and efferent targets, and the contribution of different CB1-R-expressing neurons to this pattern, are unclear. We use a combination of conventional techniques and novel genetic models to evaluate CB1-R expression in striosome (patch and matrix compartments of the striatum, and in nigral targets of striatal medium spiny projection neurons (MSNs. CB1-R protein and mRNA follow a descending dorsolateral-to-ventromedial intensity gradient in the caudal striatum, with elevated expression in striosomes relative to the surrounding matrix. The lateral predominance of striosome CB1-Rs contrasts with that of the classical striosomal marker, the mu opioid receptor (MOR, which is expressed most prominently in rostromedial striosomes. The dorsolateral-to-ventromedial CB1-R gradient is similar to Drd2 dopamine receptor immunoreactivity and opposite to Substance P. This topology of CB1-R expression is maintained downstream in the globus pallidus and substantia nigra. Dense CB1-R-expressing striatonigral fibers extend dorsally within the substantia nigra pars reticulata, and colocalize with bundles of ventrally extending, striosome-targeted, dendrites of dopamine-containing neurons in the substantia nigra pars compacta (striosome-dendron bouquets. Within striatum, CB1-Rs colocalize with fluorescently labeled MSN collaterals within the striosomes. Cre recombinase-mediated deletion of CB1-Rs from cortical projection neurons or MSNs, and MSN-selective reintroduction of CB1-Rs in knockout mice, demonstrate that the principal source of CB1-Rs in dorsolateral striosomes is local MSN collaterals

  15. Context-dependent effects of substantia nigra stimulation on eye movements.

    Science.gov (United States)

    Basso, Michele A; Liu, Ping

    2007-06-01

    In a series of now classic experiments, an output structure of the basal ganglia (BG)--the substantia nigra pars reticulata (SNr)--was shown to be involved in the generation of saccades made in particular behavioral contexts, such as when memory was required for guidance. Recent electrophysiological experiments, however, call this original hypothesis into question. Here we test the hypothesis that the SNr is involved preferentially in nonvisually guided saccades using electrical stimulation. Monkeys performed visually guided and memory-guided saccades to locations throughout the visual field. On 50% of the trials, electrical stimulation of the SNr occurred. Stimulation of the SNr altered the direction, amplitude, latency, and probability of saccades. Visually guided saccades tended to be rotated toward the field contralateral to the side of stimulation, whereas memory-guided saccades tended to be rotated toward the hemifield ipsilateral to the side of stimulation. Overall, the changes in saccade vector direction were larger for memory-guided than for visually guided saccades. Both memory- and visually guided saccades were hypometric during stimulation trials, but the stimulation preferentially affected the length of memory-guided saccades. Electrical stimulation of the SNr produced decreases in visually guided saccades bilaterally. In contrast, memory-guided saccades often had increases in saccade latency bilaterally. Finally, we found approximately 10% reduction in the probability of memory-guided saccades bilaterally. Visually guided saccade probability was unaltered. Taken together the results are consistent with the hypothesis that SNr primarily influences nonvisually guided saccades. The pattern of stimulation effects suggests that SNr influence is widespread, altering the pattern of activity bilaterally across the superior colliculus map of saccades.

  16. Mesencephalic substantia nigra and Parkinson's disease: spin-echo and inversion-recovery MRI evaluation

    International Nuclear Information System (INIS)

    Michaux, Ruben P.

    2004-01-01

    Objective: To comparatively assess the images of the mesencephalic substantia nigra (mSN) obtained with FSE (PD and T2) and IR (STIR; T1; WMS and GMS) sequences in patients with Parkinson's disease (PKD) and normal volunteers. Methods: We studied 8 normal volunteers (N group) and 8 patients (PKD groups) of similar age, both men and women, with a clinical diagnosis of PKD. We obtained axial oblique images of the mesencephalon with FSE PD and T2 sequences; Inversion-Recovery (IR) with a short inversion time (STIR); T1 weighted (IR-T1 phase reconstruction) with white matter signal suppression (IR-WMS) and gray matter signal suppression (IR-GMS). Average values were measured for: a) normalized signal intensity; b) thickness; and c) area of the mSN in each sequence and group. A statistical analysis of the values obtained for each of the variables was performed for both groups (Student and Welch correlation tests), comparing the results of the intra an inter-group sequences. A p value 0.05). Images obtained with IR-WMS and GMS sequences showed significant differences between the three variables assessed, particularly thickness and area (p<0.01), and also showed a posterolateral-anteromedial gradient in the mSN alteration in patients with PKD or recent onset and chronic evolution. Conclusions: The T2 weighted FSE sequences are not useful for the assessment of mSN, whereas PD, STIR and IR-T1 sequences allow to delineate it more accurately, without morphological differences (thickness and area), or signal intensity differences among the groups assessed. The WMS and GMS sequences showed statistically significant differences in the assessment of thickness, area and the signal intensity of the mSN, and may hence be useful for diagnosis. (author)

  17. Protein Markers of Neurotransmitter Synthesis and Release in Postmortem Schizophrenia Substantia Nigra.

    Science.gov (United States)

    Schoonover, Kirsten E; McCollum, Lesley A; Roberts, Rosalinda C

    2017-01-01

    The substantia nigra (SN) provides the largest dopaminergic input to the brain, projects to the striatum (the primary locus of action for antipsychotic medication), and receives GABAergic and glutamatergic inputs. This study used western blot analysis to compare protein levels of tyrosine hydroxylase (TH), glutamate decarboxylase (GAD67), and vesicular glutamate transporters (vGLUT1 and vGLUT2) in postmortem human SN in schizophrenia subjects (n=13) and matched controls (n=12). As a preliminary analysis, the schizophrenia group was subdivided by (1) treatment status: off medication (n=4) or on medication (n=9); or (2) treatment response: treatment resistant (n=5) or treatment responsive (n=4). The combined schizophrenia group had higher TH and GAD67 protein levels than controls (an increase of 69.6%, P=0.01 and 19.5%, P=0.004, respectively). When subdivided by medication status, these increases were found in the on-medication subjects (TH 88.3%, P=0.008; GAD67 40.6%, P=0.003). In contrast, unmedicated schizophrenia subjects had higher vGLUT2 levels than controls (an increase of 28.7%, P=0.041), but vGLUT2 levels were similar between medicated schizophrenia subjects and controls. Treatment-resistant subjects had significantly higher TH and GAD67 levels than controls (an increase of 121.0%, P=0.0003 and 58.7%, P=0.004, respectively). These data suggest increases in dopamine and GABA transmission in the SN in schizophrenia, with a potential relation to treatment and response.

  18. Gambling and the need for new responses in Public Health with an addiction "sine substantia".

    Science.gov (United States)

    Crusco, M; Massoni, F; Luzi, E; Ricci, P; Pelosi, M; Corbosiero, P; Rapp-Ricciardi, M; Ricci, S

    2016-01-01

    The Gambling Disorder (GD) was recently defined as a behavioral addiction by the "The Diagnostic and Statistical Manual of Mental Disorders IV"( DSM-V) since the clinical, neurobiological and psychopathological similarities led it to be defined it as an addiction "sine substantia". The aim of this study is to formulate an "identikit" of the gambler, to evaluate a possible association between GD / emotional specific factors and the correlation between GD / substance abuse, GD / suicide. In the study, 41 subjects were included (31 males and 10 females) and all were diagnosed with GD. A questionnaire was distributed containing 24 questions deriving from South Oaks Gambling Screen and the DSM-IVTR. The study showed that 51% of the respondents makes use of alcohol and / or drugs; that 73% of the patients started playing in order to relieve feelings of dysphoria and suffering consequences on work as well as family life (51%). A great deal of the respondents were indebted (39%) to the extent of needing to ask for loans from usurer (17%). Furthermore, 41% of the respondents in the sample showed that GD could be transformed into an alarming risk of suicide. The correlation between GD and drug abuse may depend on the brain function and the neural circuits that support impulsive behavior and the gratification mechanisms. Emotional experiences (stress, low level of education, divorce, poor social support) could constitute a possible risk factor that increases the GD. The committed offenses related to gambling could be explained by "loss of control". The results of the present study contributes to the body of knowledge regarding the size of phenomenon from a statistical and epidemiological point of view, suggesting the necessity for targeted information on the risks connected to GD in order to capture early warning signs which enables the intervention with suitable strategies.

  19. Desempenho visual de lentes de contato gelatinosas de diferentes tipos baseado na análise de frentes de onda Optical performance of different soft contact lenses based on wavefront analysis

    Directory of Open Access Journals (Sweden)

    Roberta Fagnani Gatti

    2008-12-01

    Full Text Available OBJETIVOS: Avaliar e comparar o desempenho visual, por meio da análise de frentes de onda, de seis diferentes tipos de lentes de contato gelatinosas [Cooperflex® (Coopervision, Frequency® 55 Aspheric (Coopervision, World Vision FW® (World Vision, Pure Vision® (Bausch & Lomb, Focus® Monthly (Ciba Vision, Focus® Choice AB (Ciba Vision]. MÉTODOS: Realizou-se estudo prospectivo em amostra constituída por 130 olhos de 71 indivíduos portadores de miopia ou hipermetropia até 6,00D e astigmatismo até 1,50D, com acuidade visual corrigida com óculos igual ou superior a 20/20. Os sujeitos foram inicialmente submetidos ao exame clínico oftalmológico e posteriormente, ao exame de análise de frentes de onda com o aberrômetro LADARWave® (Alcon, em duas condições: sem correção óptica e em uso de um dos tipos de lente de contato incluídos no estudo, com grau correspondente ao equivalente esférico do paciente e corrigido pela distância vértice. Para análise de resultados os indivíduos foram divididos em seis grupos similares, sendo testado em cada grupo um dos tipos de lente incluídos no estudo. RESULTADOS: Mudanças nos valores das aberrações de alta ordem foram verificadas durante uso das lentes de contato. De 130 olhos estudados, 78 apresentaram aumento no valor de RMS total durante o uso da lente. Os seis tipos de lente estudados demonstraram tendência ao aumento no valor médio de RMS total durante seu uso, sem diferença estatisticamente significante entre as mesmas. O estudo demonstrou tendência ao aumento no valor médio das aberrações tipo "coma" durante o uso das lentes. As lentes Frequency® Aspheric e Cooperflex® apresentaram melhor desempenho visual em relação ao "coma". O estudo demonstrou tendência à diminuição no valor médio das aberrações esféricas durante o uso das lentes, sendo esta tendência maior nos pacientes míopes em relação aos hipermétropes. Foi demonstrado tendência ao aumento no

  20. The GABA uptake inhibitor beta-alanine reduces pilocarpine-induced tremor and increases extracellular GABA in substantia nigra pars reticulata as measured by microdialysis.

    Science.gov (United States)

    Ishiwari, Keita; Mingote, Susana; Correa, Merce; Trevitt, Jennifer T; Carlson, Brian B; Salamone, John D

    2004-12-30

    Substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia that receives GABAergic projections from neostriatum and globus pallidus. Previous research has shown that local pharmacological manipulations of GABA in SNr can influence tremulous jaw movements in rats. Tremulous jaw movements are defined as rapid vertical deflections of the lower jaw that resemble chewing but are not directed at a particular stimulus, and evidence indicates that these movements share many characteristics with parkinsonian tremor in humans. In order to investigate the role of GABA in motor functions related to tremor, the present study tested the GABA uptake blocker beta-alanine for its ability to reduce pilocarpine-induced tremulous jaw movements. In a parallel experiment, the effect of an active dose of beta-alanine on dialysate levels of GABA in SNr was assessed using microdialysis methods. GABA levels in dialysis samples were measured using high performance liquid chromatography with electrochemical detection. beta-Alanine (250-500 mg/kg) significantly reduced tremulous jaw movements induced by pilocarpine (4.0 mg/kg). Moreover, systemic administration of beta-alanine at a dose that reduced tremulous jaw movements (500 mg/kg) resulted in a substantial increase in extracellular levels of GABA in SNr compared to the pre-injection baseline. Thus, the present results are consistent with the hypothesis that GABAergic tone in SNr plays a role in the regulation of tremulous jaw movements. This research may lead to a better understanding of how parkinsonian symptoms are modulated by SNr GABA mechanisms.

  1. Comparison of 3T and 7T susceptibility-weighted angiography of the substantia nigra in diagnosing Parkinson disease.

    Science.gov (United States)

    Cosottini, M; Frosini, D; Pesaresi, I; Donatelli, G; Cecchi, P; Costagli, M; Biagi, L; Ceravolo, R; Bonuccelli, U; Tosetti, M

    2015-03-01

    Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study. © 2015 by American Journal of Neuroradiology.

  2. Cognitive performance patterns in healthy individuals with substantia nigra hyperechogenicity and early Parkinson’s disease

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    Rezzak Yilmaz

    2016-11-01

    Full Text Available Introduction: Hyperechogenicity of the substantia nigra (SN+ is a risk marker for Parkinson’s disease (PD which can be detected before the diagnosis. In healthy individuals, SN+ has been associated with slight deficits in specific cognitive functions, suggesting cognitive impairment as a possible pre-diagnostic marker for PD. However, the pattern of cognitive deficits associated with SN+ has not yet been compared with those present in PD.Methods: Data of 262 healthy individuals with normal echogenicity (SN- and 48 healthy individuals with SN+ were compared with 82 early stage PD patients using the Consortium to Establish a Registry for Alzheimer’s disease test battery. First, the test clusters (factors were identified using a principal component analysis (PCA. Mean group performance of cognitive tests belonging to distinct factors, according to the PCA, and single subtest performances were compared using analyses of variance. Second, the number of individuals with abnormal cognitive performances (z-score <-1.0 were compared between groups. Results: Verbal memory, semantic and executive function, and praxis were identified as components of cognitive performances. The SN+ group performed significantly worse than the SN- group in tests assessing semantic and executive function, with a non-significant decrease in verbal memory. On the subtest level, individuals of the SN+ group scored significantly lower than the SN- group on the Boston Naming Test (BNT (p=0.008. In all subtests, the percentages of PD patients with values below the cut-off for abnormal performance were higher than in the SN- group. Moreover, more individuals from the SN+ group scored below the cut-off in the BNT (SN-=8.4%, SN+=20.8%, p=0.01 and TMT-B (SN-=6.9%, SN+=16.7%, p=0.02, compared to the SN- group. Conclusion: This study confirms poorer performance of healthy individuals with SN+ compared to SN- in specific cognitive domains. However, against the SN- group, the cognitive

  3. Stimulation of the substantia nigra influences the specification of memory-guided saccades

    Science.gov (United States)

    Mahamed, Safraaz; Garrison, Tiffany J.; Shires, Joel

    2013-01-01

    In the absence of sensory information, we rely on past experience or memories to guide our actions. Because previous experimental and clinical reports implicate basal ganglia nuclei in the generation of movement in the absence of sensory stimuli, we ask here whether one output nucleus of the basal ganglia, the substantia nigra pars reticulata (nigra), influences the specification of an eye movement in the absence of sensory information to guide the movement. We manipulated the level of activity of neurons in the nigra by introducing electrical stimulation to the nigra at different time intervals while monkeys made saccades to different locations in two conditions: one in which the target location remained visible and a second in which the target location appeared only briefly, requiring information stored in memory to specify the movement. Electrical manipulation of the nigra occurring during the delay period of the task, when information about the target was maintained in memory, altered the direction and the occurrence of subsequent saccades. Stimulation during other intervals of the memory task or during the delay period of the visually guided saccade task had less effect on eye movements. On stimulated trials, and only when the visual stimulus was absent, monkeys occasionally (∼20% of the time) failed to make saccades. When monkeys made saccades in the absence of a visual stimulus, stimulation of the nigra resulted in a rotation of the endpoints ipsilaterally (∼2°) and increased the reaction time of contralaterally directed saccades. When the visual stimulus was present, stimulation of the nigra resulted in no significant rotation and decreased the reaction time of contralaterally directed saccades slightly. Based on these measurements, stimulation during the delay period of the memory-guided saccade task influenced the metrics of saccades much more than did stimulation during the same period of the visually guided saccade task. Because these effects

  4. Iron concentrations and distributions in the parkinsonian substantia nigra of aged and young primate models

    International Nuclear Information System (INIS)

    Ren, M.Q.; Xie, J.P.; Wang, X.S.; Ong, W.Y.; Leong, S.K.; Watt, F.

    2001-01-01

    Parkinson's disease (PD) is a progressive neuronal degenerative brain disease of the elderly, and is caused by the selective degeneration of neurons in the substantia nigra (SN) region of the brain, resulting in a reduced production of the neurotransmitter dopamine. Iron has been linked to dopaminergic cell death in Parkinson's disease because of its potential to promote free radicals, leading to oxidative stress. The present study is aimed at using the techniques of nuclear microscopy to elucidate the iron concentrations and distributions in the SN of both young and old monkeys following unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioning. A group of three old monkeys (older than 7 years) and a group of three young monkeys (younger than 7 years) were unilaterally MPTP-lesioned (right side) to induce parkinsonism and sacrificed after 35 days. The left side SN was used as a control. This time interval was chosen to correspond to an average 50% loss of dopamine producing cells in the lesioned right side SN. We have observed a significant difference in iron concentrations between the SNs of the young and old monkeys (increasing from an average of 233 to 1092 parts per million dry weight). When comparing the lesioned and non-lesioned SNs of the same animal, we found no significant difference in iron levels for each young monkey. However we have found a slight increase in iron (approximately 10%) between the lesioned SN and control SN for old monkeys. We have also observed that in the SN of younger primates, there is a weak anti-correlation in the SN iron levels with the neuron distribution. In the older monkeys, however, we have observed a proliferation of iron-rich granules, which appear to be more strongly anti-correlated with the distribution of neurons. The iron-cell anti-correlation occurs both in the control as well as the lesioned SN. Our results suggest that iron, particularly in the form of iron-rich deposits, accumulates in specific sites

  5. Chemogenetic activation of dopamine neurons in the ventral tegmental area, but not substantia nigra, induces hyperactivity in rats

    NARCIS (Netherlands)

    Boekhoudt, Linde; Omrani, Azar; Luijendijk, Mieneke C M; Wolterink-Donselaar, Inge G; Wijbrans, Ellen C; van der Plasse, Geoffrey; Adan, Roger A H

    2016-01-01

    Hyperactivity is a core symptom in various psychiatric disorders, including attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorders, and anorexia nervosa. Although hyperactivity has been linked to dopaminergic  signalling, the causal relationship between midbrain dopamine neuronal

  6. Bilateral Acanthamoeba ulcer in a user of disposable soft contact lenses: a tragic incident or a consequence of the aggressive policy of soft contact lens trading? Úlcera bilateral por Acanthamoeba em usuária de lentes de contato gelatinosas descartáveis: um incidente trágico ou uma conseqüência da política agressiva de venda de lentes de contato gelatinosas?

    Directory of Open Access Journals (Sweden)

    Sidney Júlio de Faria e Sousa

    2008-06-01

    que, as características físicas e o regime de uso das lentes de contato gelatinosas descartáveis criam dificuldades adicionais para a vigilância médica dos seus usuários. Sem a assistência correta, eles relaxam com a rotina de limpeza, compram lentes mais baratas, usam soro fisiológico ao invés das soluções adequadas, violam os limites de uso e dormem com as mesmas. Além disso, o "marketing" agressivo e a ampla distribuição dessas lentes aumentam as chances de que pessoas, não preparadas econômica e educacionalmente, venham ter acesso às mesmas. A pergunta que fica é: Seria o presente caso um evento acidental ou um exemplo do que pode acontecer no futuro caso as lentes de contato descartáveis continuem sendo vendidas indiscriminadamente?

  7. [Effect of activation and blockade of the GABA-ergic system of the substantia nigra in the midbrain on the realization of conditioned food reflexes in dogs].

    Science.gov (United States)

    Iakimovskiĭ, A F

    1988-01-01

    Bilateral injection of 45 mcg of GABA into substantia nigra pars compacta produced in dogs a manifested improvement of parameters of the conditioned differentiation inhibition but failed to influence the positive Pavlovian alimentary conditioned reflex. Injection of GABA synaptic antagonist--picrotoxin impaired conditioned alimentary behaviour. Numerous injections of the GABAergic pharmacological agents resulted in motor disturbance--rotatory movements--and skin trophic deviations. The data obtained and literature references give ground for discussion of the role of striato-nigral and internal GABAergic substantia nigra systems in the positive modulation of adaptive alimentary behaviour and conditioned stimuli differentiation.

  8. Neuromelanin imaging of the substantia nigra and locus ceruleus among patients with Parkinson's disease using 3Tesla MRI

    International Nuclear Information System (INIS)

    Konno, Kanako; Ohtsuka, Chigumi; Kato, Kanako; Terayama, Yasuo

    2010-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder in which loss of dopaminergic neurons from the pars compacta of substantia nigra (SNc) and locus ceruleus (LC) in the major pathologic substrate. To investigate the relationships between the loss of SNc and LC neurons, and the stage of illness, we compared the signal intensity of SNc and LC between PD patients and normal controls by using a neuromelanin-sensitive magnetic resonance imaging (MRI) at 3 Tesla. We examined 41 PD patients in early stage, 10 in progressive stage, and 22 healthy controls. In PD, we observed a significant loss of neuromelanin in LC (p<0.0001) and lateral area of SNc (p=0.0011) while no significant difference between neuromelanin imaging and severity of PD was observed. The present study suggests that neuromelanin imaging using 3T MRI is a useful tool for early diagnosis of Parkinson's disease. (author)

  9. Three-dimensional magnetic resonance spectroscopic imaging in the substantia nigra of healthy controls and patients with Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Groeger, Adriane; Godau, Jana; Berg, Daniela [University of Tuebingen, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Disease (DZNE), Tuebingen (Germany); Chadzynski, Grzegorz; Klose, Uwe [University Hospital Tuebingen, Department of Diagnostic and Interventional Neuroradiology, Tuebingen (Germany)

    2011-09-15

    To investigate the substantia nigra in patients with Parkinson's disease three-dimensional magnetic resonance spectroscopic imaging with high spatial resolution at 3 Tesla was performed. Regional variations of spectroscopic data between the rostral and caudal regions of the substantia nigra as well as the midbrain tegmentum areas were evaluated in healthy controls and patients with Parkinson's disease. Nine patients with Parkinson's disease and eight age- and gender-matched healthy controls were included in this study. Data were acquired by using three-dimensional magnetic resonance spectroscopic imaging measurements. The ratios between rostral and caudal voxels of the substantia nigra as well as the midbrain tegmentum areas were calculated for the main-metabolites N-acetyl aspartate, creatine, choline, and myo-inositol. Additionally, the metabolite/creatine ratios were calculated. In all subjects spectra of acceptable quality could be obtained with a nominal voxel size of 0.252 ml. The calculated rostral-to-caudal ratios of the metabolites as well as of the metabolite/creatine ratios showed with exception of choline/creatine ratio significant differences between healthy controls and patients with Parkinson's disease. The findings from this study indicate that regional variations in N-acetyl aspartate/creatine ratios in the regions of the substantia nigra may differentiate patients with Parkinson's disease and healthy controls. (orig.)

  10. Chemical Exchange Saturation Transfer MR Imaging Is Superior to Diffusion Tensor Imaging in the Diagnosis and Severity Evaluation of Parkinson's Disease: a Study on Substantia Nigra and Striatum

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    Chunmei eLi

    2015-10-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder characterized by nigrostriatal cell loss. To date the diagnosis of PD is still based primarily on the clinical manifestations which may be typical and obvious only in advanced-stage PD. Thus, it is crucial to find a reliable marker for the diagnosis of PD. We conducted this study to assess the diagnostic efficiency of chemical-exchange-saturation-transfer (CEST imaging and diffusion-tensor imaging (DTI in PD at 3 Tesla by evaluating changes on substantia nigra and striatum. Twenty-three PD patients and twenty-three age-matched normal controls were recruited. All patients and controls were imaged on a 3 Tesla MR system, using an 8-channel head coil. CEST imaging was acquired in two transverse slices of the head, including substantia nigra and striatum. The magnetization-transfer-ratio asymmetry at 3.5 ppm, MTRasym(3.5ppm, and the total CEST signal intensity between 0 and 4 ppm were calculated. Multi-slice DTI was acquired for all the patients and normal controls. Quantitative analysis was performed on the substantia nigra, globus pallidus, putamen and caudate. The MTRasym(3.5ppm value, the total CEST signal intensity and fractional anisotropy (FA value of the substantia nigra were all significantly lower in PD patients than in normal controls (P = 0.003, P = 0.004 and P < 0.001, respectively. The MTRasym(3.5ppm values of the putamen and the caudate were significantly higher in PD patients than in normal controls (P = 0.010 and P = 0.009, respectively. There were no significant differences for the mean diffusivity (MD in these four regions between PD patients and normal controls. In conclusion, CEST MR imaging provided multiple CEST image contrasts in the substantia nigra and the striatum in PD and may be superior to DTI in the diagnosis of PD.

  11. Endomorphin-2 Inhibits the Activity of the Spinoparabrachial Projection Neuron through Presynaptic Mechanisms in the Spinal Dorsal Horn in Rats

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    Jun-Bin Yin

    2018-03-01

    Full Text Available Background/Aims: Spinal dorsal horn (SDH is one of the most important regions for analgesia produced by endomorphin-2 (EM2, which has a higher affinity and specificity for the µ-opioid receptor (MOR than morphine. Many studies have focused on substantia gelatinosa (SG, lamina II neurons to elucidate the cellular basis for its antinociceptive effects. However, the complicated types and local circuits of interneurons in the SG make it difficult to understand the real effects of EM2. Therefore, in the present study, we examined the effects of EM2 on projection neurons (PNs in lamina I. Methods: Tracing, immunofluoresence, and immunoelectron methods were used to examine the morphological connections between EM2-immunoreactive (-ir terminals and PNs. By using in vitro whole cell patch clamp recording technique, we investigated the functional effects of EM2 on PNs. Results: EM2-ir afferent terminals directly contacted PNs projecting to the parabrachial nucleus in lamina I. Their synaptic connections were further confirmed by immunoelectron microscopy, most of which were asymmetric synapses. It was found that EM2 had a strong inhibitory effect on the frequency, but not amplitude, of the spontaneous excitatory postsynaptic current (sEPSC of the spinoparabrachial PNs in lamina I, which could be reversed by MOR antagonist CTOP. However, their spontaneous inhibitory postsynaptic current (sIPSC and intrinsic properties were not changed after EM2 application. Conclusion: Applying EM2 to the SDH could produce analgesia through inhibiting the activities of the spinoparabrachial PNs in lamina I by reducing presynaptic neurotransmitters release from the primary afferent terminals.

  12. Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons

    Science.gov (United States)

    Dragicevic, Elena; Poetschke, Christina; Duda, Johanna; Schlaudraff, Falk; Lammel, Stephan; Schiemann, Julia; Fauler, Michael; Hetzel, Andrea; Watanabe, Masahiko; Lujan, Rafael; Malenka, Robert C.; Striessnig, Joerg

    2014-01-01

    Dopamine midbrain neurons within the substantia nigra are particularly prone to degeneration in Parkinson’s disease. Their selective loss causes the major motor symptoms of Parkinson’s disease, but the causes for the high vulnerability of SN DA neurons, compared to neighbouring, more resistant ventral tegmental area dopamine neurons, are still unclear. Consequently, there is still no cure available for Parkinson’s disease. Current therapies compensate the progressive loss of dopamine by administering its precursor l-DOPA and/or dopamine D2-receptor agonists. D2-autoreceptors and Cav1.3-containing L-type Ca2+ channels both contribute to Parkinson’s disease pathology. L-type Ca2+ channel blockers protect SN DA neurons from degeneration in Parkinson’s disease and its mouse models, and they are in clinical trials for neuroprotective Parkinson’s disease therapy. However, their physiological functions in SN DA neurons remain unclear. D2-autoreceptors tune firing rates and dopamine release of SN DA neurons in a negative feedback loop through activation of G-protein coupled potassium channels (GIRK2, or KCNJ6). Mature SN DA neurons display prominent, non-desensitizing somatodendritic D2-autoreceptor responses that show pronounced desensitization in PARK-gene Parkinson’s disease mouse models. We analysed surviving human SN DA neurons from patients with Parkinson’s disease and from controls, and detected elevated messenger RNA levels of D2-autoreceptors and GIRK2 in Parkinson’s disease. By electrophysiological analysis of postnatal juvenile and adult mouse SN DA neurons in in vitro brain-slices, we observed that D2-autoreceptor desensitization is reduced with postnatal maturation. Furthermore, a transient high-dopamine state in vivo, caused by one injection of either l-DOPA or cocaine, induced adult-like, non-desensitizing D2-autoreceptor responses, selectively in juvenile SN DA neurons, but not ventral tegmental area dopamine neurons. With pharmacological

  13. Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model

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    Yi Lu

    2018-02-01

    Full Text Available Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD, while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo1H nuclear magnetic resonance (NMR spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN of mice at 1, 7, and 21 days after injection of MPTP. Metabolomic analysis revealed a clear separation of the overall metabolites between PD and control mice at different time points. Glutamate (Glu in the striatum was significantly elevated at induction PD day 1 mice, which persisted to day 21. N-acetylaspartate (NAA increased in the striatum of induction PD mice on days 1 and 7, but no significant difference was found in striatum on day 21. Myo-Inositol (mI and taurine (Tau were also disturbed in the striatum in induction PD day 1 mice. Additionally, key enzymes in the glutamate-glutamine cycle were significantly increased in PD mice. These findings suggest that neuron loss and motor function impairment in induction PD mice may be linked to overactive glutamate-glutamine cycle and altered membrane metabolism.

  14. Motor stimulant effects of ethanol injected into the substantia nigra pars reticulata: importance of catalase-mediated metabolism and the role of acetaldehyde.

    Science.gov (United States)

    Arizzi-LaFrance, Maria N; Correa, Mercè; Aragon, Carlos M G; Salamone, John D

    2006-05-01

    A series of experiments was conducted to investigate the locomotor effects of local injections of ethanol and the ethanol metabolite, acetaldehyde, into substantia nigra pars reticulata (SNr). Infusions of ethanol into SNr resulted in a dose-related increase in locomotor activity, with maximal effects at a dose of 1.4 micromol. Ethanol injected into a control site dorsal to substantia nigra failed to stimulate locomotion, and another inactive site was identified in brainstem areas posterior to substantia nigra. The locomotor effects of intranigral ethanol (1.4 micromol) were reduced by coadministration of 10 mg/kg sodium azide, a catalase inhibitor that acts to reduce the metabolism of ethanol into acetaldehyde in the brain. SNr infusions of acetaldehyde, which is the first metabolite of ethanol, also increased locomotion. Taken together, these results indicate that SNr is one of the sites at which ethanol and acetaldehyde may be acting to induce locomotor activity. These results are consistent with the hypothesis that acetaldehyde is a centrally active metabolite of ethanol, and provide further support for the idea that catalase activity is a critical step in the regulation of ethanol-induced motor activity. These studies have implications for understanding the brain mechanisms involved in mediating the ascending limb of the biphasic dose-response curve for the effect of ethanol on locomotor activity.

  15. Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinson's rats.

    Science.gov (United States)

    Cho, Han-Sam; Shin, Mal-Soon; Song, Wook; Jun, Tae-Won; Lim, Baek-Vin; Kim, Young-Pyo; Kim, Chang-Ju

    2013-01-01

    Progressive loss of dopaminergic neurons in substantia nigra is a key pathogenesis of Parkinson's disease. In the present study, we investigated the effects of treadmill exercise on short-term memory, apoptotic dopaminergic neuronal cell death and fiber loss in the nigrostriatum, and cell proliferation in the hippocampal dentate gyrus of Parkinson's rats. Parkinson's rats were made by injection of 6-hydroxydopamine (6-OHDA) into the striatum using stereotaxic instrument. Four weeks after 6-OHDA injection, the rats in the 6-OHDA-injection group exhibited significant rotational asymmetry following apomorphine challenge. The rats in the exercise groups were put on the treadmill to run for 30 min once a day for 14 consecutive days starting 4 weeks after 6-OHDA injection. In the present results, extensive degeneration of the dopaminergic neurons in the substantia nigra with loss of dopaminergic fibers in the striatum were produced in the rats without treadmill running, which resulted in short-term memory impairment. However, the rats performing treadmill running for 2 weeks alleviated nigrostriatal dopaminergic cell loss and alleviated short-term memory impairment with increasing cell proliferation in the hippocampal dentate gyrus of Parkinson's rats. The present results show that treadmill exercise may provide therapeutic value for the Parkinson's disease.

  16. Impact of Combined Subthalamic Nucleus and Substantia Nigra Stimulation on Neuropsychiatric Symptoms in Parkinson’s Disease Patients

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    U. Hidding

    2017-01-01

    Full Text Available The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN and combined subthalamic nucleus and substantia nigra (STN+SNr high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson’s disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson’s disease (1 female; age: 61.3±7.3 years; disease duration: 12.3±5.4 years; Hoehn and Yahr stage: 2.2±0.39 were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS, Modified Fatigue Impact Scale (MFIS, Becks Depression Inventory (BDI-I, Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale (QUIP-RS, and Parkinson’s Disease Questionnaire (PDQ-39. Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended.

  17. Magnetic Resonance Imaging Biomarkers to Assess Substantia Nigra Damage in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

    Science.gov (United States)

    Pyatigorskaya, Nadya; Gaurav, Rahul; Arnaldi, Dario; Leu-Semenescu, Smaranda; Yahia-Cherif, Lydia; Valabregue, Romain; Vidailhet, Marie; Arnulf, Isabelle; Lehéricy, Stephane

    2017-11-01

    Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered to be a prodromal stage of Parkinson's disease (PD). At PD onset, 40 to 70% of the dopaminergic neurons in the substantia nigra (SN) are already lost. Thus, milder SN damage is expected in participants with iRBD. We aimed to quantify SN damage in participants with iRBD using multimodal magnetic resonance imaging (MRI) and to determine biomarker efficacy in preclinical Parkinsonism. Nineteen participants with iRBD and 18 controls underwent 3-Tesla MRI, including diffusion tensor imaging, neuromelanin (NM)-sensitive imaging, and T2* mapping. Regions of interest in the SN area were drawn in NM-sensitive and T2-weighted images. The volume and normalized signal intensity in NM-sensitive images, R2*, and diffusion tensor measures were quantified in the SN. Additionally, two raters performed visual analysis of the SN using the NM-sensitive images. Participants with iRBD showed a reduction in the NM-sensitive volume and signal intensity and a decrease in fractional anisotropy (FA) versus controls, but showed no differences in axial, radial, or mean diffusivity or in R2*. For NM-sensitive volume and signal intensity, the receiver operating characteristic analysis discriminated between participants with iRBD and controls with a diagnostic accuracy of 0.86 and 0.79, respectively, whereas the accuracy was 0.77 for FA. The three biomarkers had a combined accuracy of 0.92. The fraction of participants correctly characterized by visual assessment was 0.81. NM-sensitive imaging and FA allowed for the detection of SN damage in participants with iRBD with good diagnostic accuracy. These measures may represent valuable biomarkers for prodromal Parkinsonism. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  18. Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses

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    Diego Iacono

    2015-05-01

    Full Text Available Background: Dystonias (Dys represent the third most common movement disorder after essential tremor (ET and Parkinson's disease (PD. While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions of Dys brains, mostly in the basal ganglia (BG, and specifically in the substantia nigra (SN. Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies. Methods: Quantitative immunohistochemistry protocols were used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age‐matched control subjects (C. Results: We observed a significant reduction (∼20% of pigmented neurons in the SN of Dys compared to C (p<0.01. Neither significant volumetric changes nor evident neurodegenerative signs were observed in the remaining pool of nigral pigmented neurons in Dys brains. These novel quantitative findings were confirmed after exclusion of possible co‐occurring SN pathologies including Lewy pathology, tau‐neurofibrillary tangles, β‐amyloid deposits, ubiquitin (ubiq, and phosphorylated‐TAR DNA‐binding protein 43 (pTDP43‐positive inclusions. Discussion: A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN.

  19. Metabolism regulates the spontaneous firing of substantia nigra pars reticulata neurons via KATP and nonselective cation channels.

    Science.gov (United States)

    Lutas, Andrew; Birnbaumer, Lutz; Yellen, Gary

    2014-12-03

    Neurons use glucose to fuel glycolysis and provide substrates for mitochondrial respiration, but neurons can also use alternative fuels that bypass glycolysis and feed directly into mitochondria. To determine whether neuronal pacemaking depends on active glucose metabolism, we switched the metabolic fuel from glucose to alternative fuels, lactate or β-hydroxybutyrate, while monitoring the spontaneous firing of GABAergic neurons in mouse substantia nigra pars reticulata (SNr) brain slices. We found that alternative fuels, in the absence of glucose, sustained SNr spontaneous firing at basal rates, but glycolysis may still be supported by glycogen in the absence of glucose. To prevent any glycogen-fueled glycolysis, we directly inhibited glycolysis using either 2-deoxyglucose or iodoacetic acid. Inhibiting glycolysis in the presence of alternative fuels lowered SNr firing to a slower sustained firing rate. Surprisingly, we found that the decrease in SNr firing was not mediated by ATP-sensitive potassium (KATP) channel activity, but if we lowered the perfusion flow rate or omitted the alternative fuel, KATP channels were activated and could silence SNr firing. The KATP-independent slowing of SNr firing that occurred with glycolytic inhibition in the presence of alternative fuels was consistent with a decrease in a nonselective cationic conductance. Although mitochondrial metabolism alone can prevent severe energy deprivation and KATP channel activation in SNr neurons, active glucose metabolism appears important for keeping open a class of ion channels that is crucial for the high spontaneous firing rate of SNr neurons. Copyright © 2014 the authors 0270-6474/14/3416336-12$15.00/0.

  20. Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats.

    Science.gov (United States)

    Zaitone, Sawsan A; Abo-Elmatty, Dina M; Elshazly, Shimaa M

    2012-01-01

    To evaluate the neuroprotective effect of the nootropic drugs, piracetam (PIR) and vinpocetine (VIN), in rotenone-induced Parkinsonism in rats. Sixty male rats were divided into 6 groups of 10 rats each. The groups were administered vehicle, control (rotenone, 1.5 mg/kg/48 h/6 doses, s.c.), PIR (100 and 200 mg/kg/day, p.o.) and VIN (3 and 6 mg/kg/day, p.o.). The motor performance of the rats was evaluated by the open field and pole test. Striatal dopamine level, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor-α (TNF-α) were assayed. Histopathological study of the substantia nigra was also done. Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field test. In addition, GSH level was decreased whereas MDA and TNF-α increased in striata of rotenone-treated rats as compared to vehicle-treated rats. Marked degeneration of the substantia nigra pars compacta (SNpc) neurons and depletion of striatal dopamine was also observed in the rotenone-treated rats. Treatment with PIR or VIN significantly reversed the locomotor deficits and increased striatal dopamine level. Treatment with VIN significantly (P<0.05) reduced the striatal level of MDA and GSH in comparison to rotenone group whereas TNF-α production was found to be significantly decreased in PIR group (P<0.05). VIN and PIR exhibit neuroprotective activity in rotenone-induced Parkinsonism. Hence, these nootropic agents may be considered as possible candidates in the treatment of Parkinson's disease.

  1. Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of ?-synuclein aggregation and programmed cell death

    OpenAIRE

    Wang, Yi-Ting; Lin, Hui-Ching; Zhao, Wei-Zhong; Huang, Hui-Ju; Lo, Yu-Li; Wang, Hsiang-Tsui; Maan-Yuh Lin, Anya

    2017-01-01

    Clinical studies report significant increases in acrolein (an ?,?-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson?s disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150?nmoles/0.5??l) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) leve...

  2. Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

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    Wuisman Piet GWM

    2007-09-01

    Full Text Available Abstract Background Parkinson's disease (PD is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD. We have therefore set out to conduct a prospective study testing the diagnostic accuracy of TCD in patients with a parkinsonism of unclear origin. Methods/Design We will enrol 250 consecutive patients, who are referred to neurology outpatient clinics of two teaching hospitals, for analysis of clinically unclear parkinsonism. Patients, whose parkinsonism is clearly diagnosable at the first visit, will be excluded from the study. All patients will undergo a TCD of the substantia nigra. As a surrogate gold standard we will use the consensus clinical diagnosis reached by two independent, blinded, movement disorder specialist neurologists after 2 years follow-up. At the time of TCD, patients will also undergo a SPECT scan of the brain. Discussion As this prospective trial enrols only patients with an early-stage parkinsonism, it will yield data on the diagnostic accuracy of TCD that is relevant to daily clinical practice: The neurologist needs a diagnostic tool that provides additional information in patients with a clinically indefinable parkinsonian syndrome. The above described observational longitudinal study was designed to explicitly study this aspect in the diagnostic process. Trial registration (ITRSCC NCT00368199

  3. Cell survival and differentiation with nanocrystalline glass-like carbon using substantia nigra dopaminergic cells derived from transgenic mouse embryos.

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    Noela Rodriguez-Losada

    Full Text Available Regenerative medicine requires, in many cases, physical supports to facilitate appropriate cellular architecture, cell polarization and the improvement of the correct differentiation processes of embryonic stem cells, induced pluripotent cells or adult cells. Because the interest in carbon nanomaterials has grown within the last decade in light of a wide variety of applications, the aim of this study was to test and evaluate the suitability and cytocompatibility of a particular nanometer-thin nanocrystalline glass-like carbon film (NGLC composed of curved graphene flakes joined by an amorphous carbon matrix. This material is a disordered structure with high transparency and electrical conductivity. For this purpose, we used a cell line (SN4741 from substantia nigra dopaminergic cells derived from transgenic mouse embryos. Cells were cultured either in a powder of increasing concentrations of NGLC microflakes (82±37μm in the medium or on top of nanometer-thin films bathed in the same culture medium. The metabolism activity of SN4741 cells in presence of NGLC was assessed using methylthiazolyldiphenyl-tetrazolium (MTT and apoptosis/necrosis flow cytometry assay respectively. Growth and proliferation as well as senescence were demonstrated by western blot (WB of proliferating cell nuclear antigen (PCNA, monoclonal phosphorylate Histone 3 (serine 10 (PH3 and SMP30 marker. Specific dopaminergic differentiation was confirmed by the WB analysis of tyrosine hydroxylase (TH. Cell maturation and neural capability were characterized using specific markers (SYP: synaptophysin and GIRK2: G-protein-regulated inward-rectifier potassium channel 2 protein via immunofluorescence and coexistence measurements. The results demonstrated cell positive biocompatibility with different concentrations of NGLC. The cells underwent a process of adaptation of SN4741 cells to NGLC where their metabolism decreases. This process is related to a decrease of PH3 expression and

  4. Regional distribution of enkephalinase in rat brain by autoradiography

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    Waksman, G.; Hamel, E.; Besselievre, R.; Fournie-Zaluski, M.C.; Roques, B.P.; Bouboutou, R.

    1984-01-01

    The first visualization of enkephalinase (neutral metalloendopeptidase, E.C.3.4.24.11) in rat brain was obtained by autoradiography, using a new tritiated inhibitor: [ 3 H]N-[(R, S) 3-(N-hydroxy) carboxamido-2-benzyl propanoyl]-glycine ( 3 H-HCBP-Gly). The preliminary analysis of sections clearly showed a discrete localization of enkephalinase in enkephalin enriched regions, such as caudate nucleus, putamen, globus pallidus, and substantia nigra. Moreover 3 H-HCBP-Gly binding also occured in choroid plexus and spinal cord [fr

  5. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

    International Nuclear Information System (INIS)

    Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.; Liu Tao; Yue, H.-Y.; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-01-01

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na + -channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  6. Effects of [Des-Tyr1]-γ-endorphin and α-endorphin on substantia nigra self-stimulation

    NARCIS (Netherlands)

    Dorsa, D.M.; Ree, J.M. van; Wied, D. de

    The β-lipotropin fragments, [des-Tyr1]-γ-endorphin (DTγE, β-LPH62–77) and α-endorphin (β-LPH61–76) affect self-stimulating behavior associated with electrical stimulation of neurons of the ventral tegmentum area of rats in an opposite way. Subcutaneous administration of DTγE (5 and 25 μg) attenuated

  7. [Effect of stimulation of GABA-ergic structures of the substantia nigra and caudate nucleus on food-getting behavior in the cat].

    Science.gov (United States)

    Shugalev, N P

    1983-01-01

    A study was made of the functional significance of GABA-ergic structures of the substantia nigra (SN) and the caudate nucleus (CN) and their role in food-procuring behaviour of cats. Analysis was made of behavioral and EEG-effects of local GABA and the GABA antagonist, picrotoxin, microinjections into the studied brain structures. Stimulation of the GABA-ergic structures of the SN produced a sedative effect and depression of the cat food-procuring behaviour. Effects of stimulation of the CN GABA-ergic structures were to a great degree reverse. The conclusion has been made that GABA-ergic structures of the SN and the CN play different roles in controlling the CN inhibitory influence upon food-procuring behaviour.

  8. 6-OHDA induced calcium influx through N-type calcium channel alters membrane properties via PKA pathway in substantia nigra pars compacta dopaminergic neurons.

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    Qu, Liang; Wang, Yuan; Zhang, Hai-Tao; Li, Nan; Wang, Qiang; Yang, Qian; Gao, Guo-Dong; Wang, Xue-Lian

    2014-07-11

    Voltage gated calcium channels (VGCC) are sensitive to oxidative stress, and their activation or inactivation can impact cell death. Although these channels have been extensively studied in expression systems, their role in the brain, particularly in the substantia nigra pars compacta (SNc), remain controversial. In this study, we assessed 6-hydroxydopamine (6-OHDA) induced transformation of firing pattern and functional changes of calcium channels in SNc dopaminergic neurons. Application of 6-OHDA (0.5-2mM) evoked a dose-dependent, desensitizing inward current and intracellular free calcium concentration ([Ca(2+)]i) rise. In voltage clamp, ω-conotoxin-sensitive Ca(2+) current modulation mediated by 6-OHDA reflected an altered sensitivity. Furthermore, we found that 6-OHDA modulated Ca(2+) currents through PKA pathway. These results provided evidence for the potential role of VGCCs and PKA involved in oxidative stress in degeneration of SNc neurons in Parkinson's disease (PD). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Overexpression of parkin in rat nigrostriatal dopamine system protects against methamphetamine neurotoxicity

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    Liu, Bin; Traini, Roberta; Killinger, Bryan; Schneider, Bernard; Moszczynska, Anna

    2013-01-01

    Methamphetamine (METH) is a central nervous system psychostimulant with a high potential for abuse. At high doses, METH causes a selective degeneration of dopaminergic terminals in the striatum, sparing other striatal terminals and cell bodies. We previously detected a deficit in parkin after binge METH in rat striatal synaptosomes. Parkin is an ubiquitin-protein E3 ligase capable of protecting dopamine neurons from diverse cellular insults. Whether the deficit in parkin mediates the toxicity of METH and whether parkin can protect from toxicity of the drug is unknown. The present study investigated whether overexpression of parkin attenuates degeneration of striatal dopaminergic terminals exposed to binge METH. Parkin overexpression in rat nigrostriatal dopamine system was achieved by microinjection of adeno-associated viral transfer vector 2/6 encoding rat parkin (AAV2/6-parkin) into the substantia nigra pars compacta. The microinjections of AAV2/6-parkin dose-dependently increased parkin levels in both the substantia nigra pars compacta and striatum. The levels of dopamine synthesizing enzyme, tyrosine hydroxylase, remained at the control levels; therefore, tyrosine hydroxylase immunoreactivity was used as an index of dopaminergic terminal integrity. In METH-exposed rats, the increase in parkin levels attenuated METH-induced decreases in striatal tyrosine hydroxylase immunoreactivity in a dose-dependent manner, indicating that parkin can protect striatal dopaminergic terminals against METH neurotoxicity. PMID:23313192

  10. Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

    Science.gov (United States)

    Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

    2015-12-16

    Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both

  11. Protective role of apigenin on rotenone induced rat model of Parkinson's disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis.

    Science.gov (United States)

    Anusha, Chandran; Sumathi, Thangarajan; Joseph, Leena Dennis

    2017-05-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra which is associated with oxidative stress, neuroinflammation and apoptosis. Apigenin (AGN), a non-mutagenic flavone found in fruits and vegetables, exhibits a variety of biological effects including anti-apoptotic, anti-inflammatory, and free radical scavenging activities. The current study was aimed to investigate the neuroprotective effects and molecular mechanisms of AGN in a rat model of PD induced by rotenone (ROT). Unilateral stereotaxic intranigral infusion of ROT caused the loss of tyrosine hydroxylase (TH) immunoreactivity in striatum and substantia nigra. AGN treatment (10 and 20 mg/kg, i.p.) showed a significant improvement in behavioral, biochemical and mitochondrial enzyme activities as compared to ROT exposed rats. The mRNA expression of inflammatory markers and neurotrophic factors was quantified by reverse transcriptase polymerase chain reaction (RT-PCR). Administration of AGN significantly attenuated the upregulation of NF-κB gene expression in ROT induced group and prevented the neuroinflammation in substantia nigra pars compacta (SNpc). Further, AGN inhibited the release of pro-inflammatory cytokines TNF- α, IL-6 and pro-inflammatory enzyme iNOS-1 induced by ROT. Additionally, AGN prevents the reduction of neurotrophic factors BDNF and GDNF mRNA expression in ROT lesioned rats. Immunoblot results illustrated that AGN treatment downregulated α-synuclein aggregation and upregulated the TH protein expression as well as dopamine D2 receptor (D2R) expression in ROT lesioned rats. Thus, the present findings collectively suggest that AGN exerts its neuroprotection in ROT model of PD and may act as an effective agent for treatment of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Control of the subthalamic innervation of substantia nigra pars reticulata by D1 and D2 dopamine receptors.

    Science.gov (United States)

    Ibañez-Sandoval, Osvaldo; Hernández, Adán; Florán, Benjamin; Galarraga, Elvira; Tapia, Dagoberto; Valdiosera, Rene; Erlij, David; Aceves, Jorge; Bargas, José

    2006-03-01

    The effects of activating dopaminergic D1 and D2 class receptors of the subthalamic projections that innervate the pars reticulata of the subtantia nigra (SNr) were explored in slices of the rat brain using the whole cell patch-clamp technique. Excitatory postsynaptic currents (EPSCs) that could be blocked by 6-cyano-7-nitroquinoxalene-2,3-dione and D-(-)-2-amino-5-phosphonopentanoic acid were evoked onto reticulata GABAergic projection neurons by local field stimulation inside the subthalamic nucleus in the presence of bicuculline. Bath application of (RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF-38393), a dopaminergic D1-class receptor agonist, increased evoked EPSCs by approximately 30% whereas the D2-class receptor agonist, trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo(3,4-g)quinoline (quinpirole), reduced EPSCs by approximately 25%. These apparently opposing actions were blocked by the specific D1- and D2-class receptor antagonists: R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepinehydrochloride (SCH 23390) and S-(-)-5-amino-sulfonyl-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride), respectively. Both effects were accompanied by changes in the paired-pulse ratio, indicative of a presynaptic site of action. The presynaptic location of dopamine receptors at the subthalamonigral projections was confirmed by mean-variance analysis. The effects of both SKF-38393 and quinpirole could be observed on terminals contacting the same postsynaptic neuron. Sulpiride and SCH 23390 enhanced and reduced the evoked EPSC, respectively, suggesting a constitutive receptor activation probably arising from endogenous dopamine. These data suggest that dopamine presynaptically modulates the subthalamic projection that targets GABAergic neurons of the SNr. Implications of this modulation for basal ganglia function are discussed.

  13. Development of striatal patch/matrix organization in organotypic co-cultures of perinatal striatum, cortex and substantia nigra.

    Science.gov (United States)

    Snyder-Keller, A; Costantini, L C; Graber, D J

    2001-01-01

    Organotypic cultures of fetal or early postnatal striatum were used to assess striatal patch formation and maintenance in the presence or absence of dopaminergic and glutamatergic influences. Vibratome-cut slices of the striatum prepared from embryonic day 19 to postnatal day 4 rat pups were maintained in static culture on clear membrane inserts in Dulbecco's modified Eagle's medium/F12 (1:1) with 20% horse serum. Some were co-cultured with embryonic day 12-16 ventral mesencephalon and/or embryonic day 19 to postnatal day 4 cortex, which produced a dense dopaminergic innervation and a modest cortical innervation. Donors of striatal and cortical tissue were previously injected with bromo-deoxyuridine (BrdU) on embryonic days 13 and 14 in order to label striatal neurons destined to populate the patch compartment of the striatum. Patches of BrdU-immunoreactive cells were maintained in organotypic cultures of late prenatal (embryonic days 20-22) or early postnatal striatum in the absence of nigral dopaminergic or cortical glutamatergic influences. In slices taken from embryonic day 19 fetuses prior to the time of in vivo patch formation, patches were observed to form after 10 days in vitro, in 39% of nigral-striatal co-cultures compared to 6% of striatal slices cultured alone or in the presence of cortex only. Patches of dopaminergic fibers, revealed by tyrosine hydroxylase immunoreactivity, were observed in the majority of nigral-striatal co-cultures. Immunostaining for the AMPA-type glutamate receptor GluR1 revealed a dense patch distribution in nearly all cultures, which developed in embryonic day 19 cultures after at least six days in vitro. These findings indicate that striatal patch/matrix organization is maintained in organotypic culture, and can be induced to form in vitro in striatal slices removed from fetuses prior to the time of in vivo patch formation. Furthermore, dopaminergic innervation from co-cultured pieces of ventral mesencephalon enhances patch

  14. Chronic organic manganese administration in the rat does not damage dopaminergic nigrostriatal neurons.

    Science.gov (United States)

    Yong, V W; Perry, T L; Godolphin, W J; Jones, K A; Clavier, R M; Ito, M; Foulks, J G

    1986-01-01

    In an attempt to produce an animal model of Parkinson's disease, we injected rats repeatedly with high doses of methylcyclopentadienyl manganese tricarbonyl (MMT), a compound which has been reported to lower striatal dopamine content in mice. Chronic MMT administration for up to 5 months, even though it produced a substantial elevation in brain manganese content during the period of exposure, did not destroy dopaminergic nigrostriatal neurons. This was assessed by measurements of tyrosine hydroxylase activity and contents of dopamine and its metabolites in the striatum, and by histological examination of the substantia nigra. Our results differ from those of others who administered manganese chloride in drinking water to rats. This discrepancy is unlikely to be a consequence of differences in duration of exposure or route of administration. It could be due to our having used an organic rather than an inorganic manganese compound, or to a species difference in vulnerability to organic manganese between rats and mice.

  15. Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease.

    Science.gov (United States)

    Chao, Yin Xia; He, Bei Ping; Tay, Samuel Sam Wah

    2009-11-30

    Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons.

  16. Clinical features and dysfunctions of iron metabolism in Parkinson disease patients with hyper echogenicity in substantia nigra: a cross-sectional study.

    Science.gov (United States)

    Yu, Shu-Yang; Cao, Chen-Jie; Zuo, Li-Jun; Chen, Ze-Jie; Lian, Teng-Hong; Wang, Fang; Hu, Yang; Piao, Ying-Shan; Li, Li-Xia; Guo, Peng; Liu, Li; Yu, Qiu-Jin; Wang, Rui-Dan; Chan, Piu; Chen, Sheng-di; Wang, Xiao-Min; Zhang, Wei

    2018-01-17

    Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group (P hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

  17. In parkinsonian substantia nigra, alpha-synuclein is modified by acrolein, a lipid-peroxidation product, and accumulates in the dopamine neurons with inhibition of proteasome activity.

    Science.gov (United States)

    Shamoto-Nagai, M; Maruyama, W; Hashizume, Y; Yoshida, M; Osawa, T; Riederer, P; Naoi, M

    2007-01-01

    alpha-Synuclein (alphaSYN) plays a central role in the neural degeneration of Parkinson's disease (PD) through its conformational change. In PD, alphaSYN, released from the membrane, accumulates in the cytoplasm and forms Lewy body. However, the mechanism behind the translocation and conformational change of alphaSYN leading to the cell death has not been well elucidated. This paper reports that in the dopamine neurons of the substantia nigra containing neuromelanin from PD patients, alphaSYN was modified with acrolein (ACR), an aldehyde product of lipid peroxidation. Histopathological observation confirmed the co-localization of protein immunoreactive to anti-alphaSYN and ACR antibody. By Western blot analyses of samples precipitated with either anti-alphaSYN or anti-ACR antibody, increase in ACR-modified alphaSYN was confirmed in PD brain. Modification of recombinant alphaSYN by ACR enhanced its oligomerization, and at higher ACR concentrations alphaSYN was fragmented and polymerized forming a smear pattern in SDS-PAGE. ACR reduced 20S proteasome activity through the direct modification of the proteasome proteins and the production of polymerized ACR-modified proteins, which inhibited proteasome activity in vitro. These results suggest that ACR may initiate vicious cycle of modification and aggregation of proteins, including alphaSYN, and impaired proteolysis system, to cause neuronal death in PD.

  18. Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson's disease: A diagnostic performance study and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Fabiana C.C.; Vieira, Gilson; Lucato, Leandro T.; Leite, Claudia C.; Pastorello, Bruno F.; Otaduy, Maria C.G.; Chaim, Khallil T.; Campanholo, Kenia R. [University of Sao Paulo, LIM-44, Department of Radiology, Sao Paulo, SP (Brazil); Sato, Joao R. [University of Sao Paulo, LIM-44, Department of Radiology, Sao Paulo, SP (Brazil); Universidade Federal do ABC, Center of Mathematics, Computation and Cognition, Santo Andre (Brazil); Bor-Seng-Shu, Edson; Novaes, Natalia P. [Hospital Israelita Albert Einstein, Sao Paulo (Brazil); University of Sao Paulo, Department of Neurology, Sao Paulo (Brazil); Magalhaes Melo, Luciano; Goncalves, Marcia R.; Reis Barbosa, Egberto [University of Sao Paulo, Department of Neurology, Sao Paulo (Brazil); Pereira do Nascimento, Felipe Barjud; Amaro, Edson [University of Sao Paulo, LIM-44, Department of Radiology, Sao Paulo, SP (Brazil); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Jacobsen Teixeira, Manoel [University of Sao Paulo, Department of Neurosurgery, Sao Paulo (Brazil); Cardoso, Ellison Fernando [University of Sao Paulo, LIM-44, Department of Radiology, Sao Paulo, SP (Brazil); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Institute of Mathematics and Statistics University of Sao Paulo (IME-USP), Sao Paulo (Brazil)

    2017-06-15

    Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy. Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures. In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I{sup 2} = 91.9 %). SN-FA cannot be used as an isolated measure to diagnose PD. (orig.)

  19. Intracranial dialysis measurement of oxytocin, monoamine and uric acid release from the olfactory bulb and substantia nigra of sheep during parturition, suckling, separation from lambs and eating.

    Science.gov (United States)

    Kendrick, K M; Keverne, E B; Chapman, C; Baldwin, B A

    1988-01-26

    Intracranial dialysis was used to measure the release of oxytocin (OXY), monoamines and their metabolites and uric acid (UA) from the substantia nigra (SN) and olfactory bulb (OB) of sheep during parturition, suckling, separation from lambs and eating. Results showed that OXY concentrations increased significantly during parturition, suckling and eating in the SN and during parturition and suckling in the OB. Concentrations of dopamine (DA) increased significantly in the SN during suckling and eating and in the OB during parturition and suckling. The dopamine metabolite, homovanillic acid, also increased significantly in the SN during parturition. Concentrations of the noradrenaline metabolite, 4-hydroxy-3-methoxyphenylethan-1,2-diol (MHPG) and the purine metabolite, UA, were significantly raised during parturition, suckling and separation from the lambs in the SN and increased UA levels were also found during eating. In a separate experiment it was confirmed that OXY was detectable in homogenates of both the SN and the OB. These results show that, in the sheep, OXY and DA release in the SN is associated with maternal and ingestive behaviour whereas similar release in the OB may only be related to maternal behaviour. Release of MHPG in the SN may be associated with maternal behaviour and/or stress.

  20. Secondary parkinsonism due to focal substantia nigra lesions. A PET study with [18F]FDG and [18F]fluorodopa

    International Nuclear Information System (INIS)

    Boecker, H.; Weindl, A.; Kruggel, F.; Graerin v. Einsiedel, H.; Contrad, B.; Leenders, K.; Antonini, A.; Kuwert, T.

    1996-01-01

    We present a 71 year old woman with predominantly right sided parkinsonim of sudden onset, but without tremor. Magnetic resonance imaging (MRI) depicted lesions affecting the substantia nigra (SN) bilaterally, but more pronounced on the left side. There were no other discernible structural lesions. Using positron emission tomography (PET), we investigated regional cerebral metabolic rate of glucose (rCMRG) using the tracer [ 18 F]-fluorodeoxyglucose (FDG), and striatal dopa decarboxylase capacity using the tracer [ 18 F]-L-6-fluorodopa (FDOPA). The degree and pattern of distribution of FDOPA uptake reductions (putamen > caudate nuclei) were similar to those in idopathic Parkinson's disease (PD). FDG uptake also revealed similar changes (reductions in frontal cortex and cerebellum, but increases in thalamus), except for putamen which showed reduced rCMRG. In conclusion, the absence of tremor at rest accords with experimental SN lesions. The PET findings in this atypical condition are explained in terms of deafferentation of various brain regions involved in motor control. Furthermore, they illustrate the metabolic effects related to acute focal lesions of the SN as opposed to the progressive degeneration in idiopathic PD and may serve to help unravel the complicated pathophysiology underlying these conditions. (au) 39 refs

  1. Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain.

    Science.gov (United States)

    Lindefors, N; Brene, S; Herrera-Marschitz, M; Persson, H

    1989-01-01

    In situ hybridization histochemistry and RNA blots were used to study the expression of glutamic acid decarboxylase (GAD) mRNA in rats with or without a unilateral lesion of midbrain dopamine neurons. Two populations of GAD mRNA positive neurons were found in the intact caudate-putamen, substantia nigra and fronto-parietal cortex. In caudate-putamen, only one out of ten of the GAD mRNA positive neurons expressed high levels, while in substantia nigra every second of the positive neurons expressed high levels of GAD mRNA. Relatively few, but intensively labelled neurons were found in the intact fronto-parietal cerebral cortex. In addition, one out of six of the GAD mRNA positive neurons in the fronto-parietal cortex showed a low labeling. On the ipsilateral side, the forebrain dopamine deafferentation induced an increase in the number of neurons expressing high levels of GAD mRNA in caudate-putamen, and a decrease in fronto-parietal cortex. A smaller decrease was also seen in substantia nigra. However, the total number of GAD mRNA positive neurons were not significantly changed in any of these brain regions. The changes in the levels of GAD mRNA after the dopamine lesion were confirmed by RNA blot analysis. Hence, midbrain dopamine neurons appear to control neuronal expression of GAD mRNA by a tonic down-regulation in a fraction of GAD mRNA positive neurons in caudate-putamen, and a tonic up-regulation in a fraction of GAD mRNA positive neurons in fronto-parietal cortex and substantia nigra.

  2. Analysis of the Substantia Innominata Volume in Patients with Parkinson’s Disease with Dementia, Dementia with Lewy Bodies, and Alzheimer’s Disease

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    Kim, Hee Jin; Lee, Ji Eun; Shin, Soo Jeong; Sohn, Young Ho; Lee, Phil Hyu

    2011-01-01

    Background and Purpose The substantia innominata (SI) contains the nucleus basalis of Meynert, which is the major source of cholinergic input to the cerebral cortex. We hypothesized that degeneration of the SI and its relationship to general cognitive performance differs in amyloidopathy and synucleinopathy. Methods We used magnetic resonance imaging (MRI)-based volumetric analysis to evaluate the SI volume in patients with amnestic mild cognitive impairment (aMCI), Alzheimer’s disease (AD), Parkinson’s disease-mild cognitive impairment (PD-MCI), PD with dementia (PDD), dementia with Lewy bodies (DLB), and healthy elderly controls. The correlation between SI volume and general cognitive performance, measured using the Korean version of the Mini-Mental State Examination (K-MMSE), was examined. Results Compared to control subjects, the mean normalized SI volume was significantly decreased in all of the other groups. The normalized SI volume did not differ between the subjects with PDD and DLB, whereas it was significantly smaller in subjects with PDD (p = 0.029) and DLB (p = 0.011) compared with AD. In subjects with PD-related cognitive impairment (PD-MCI, PDD, or DLB), there was a significant positive correlation between the SI volume and K-MMSE score (r = 0.366, p < 0.001), whereas no correlation was seen in subjects with AD-related cognitive impairment (aMCI or AD). Conclusions Our data suggest that the SI loss is greater in synucleinopathy-related dementia (PDD or DLB) than in AD and that the contribution of the SI to cognitive performance is greater in synucleinopathy than in amyloidopathy. PMID:24868398

  3. Analysis of the Substantia Innominata Volume in Patients with Parkinson’s Disease with Dementia, Dementia with Lewy Bodies, and Alzheimer’s Disease

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    Hee Jin Kim

    2011-10-01

    Full Text Available Background and Purpose The substantia innominata (SI contains the nucleus basalis of Meynert, which is the major source of cholinergic input to the cerebral cortex. We hypothesized that degeneration of the SI and its relationship to general cognitive performance differs in amyloidopathy and synucleinopathy. Methods We used magnetic resonance imaging (MRI-based volumetric analysis to evaluate the SI volume in patients with amnestic mild cognitive impairment (aMCI, Alzheimer’s disease (AD, Parkinson’s disease-mild cognitive impairment (PD-MCI, PD with dementia (PDD, dementia with Lewy bodies (DLB, and healthy elderly controls. The correlation between SI volume and general cognitive performance, measured using the Korean version of the Mini-Mental State Examination (K-MMSE, was examined. Results Compared to control subjects, the mean normalized SI volume was significantly decreased in all of the other groups. The normalized SI volume did not differ between the subjects with PDD and DLB, whereas it was significantly smaller in subjects with PDD (p = 0.029 and DLB (p = 0.011 compared with AD. In subjects with PD-related cognitive impairment (PD-MCI, PDD, or DLB, there was a significant positive correlation between the SI volume and K-MMSE score (r = 0.366, p < 0.001, whereas no correlation was seen in subjects with AD-related cognitive impairment (aMCI or AD. Conclusions Our data suggest that the SI loss is greater in synucleinopathy-related dementia (PDD or DLB than in AD and that the contribution of the SI to cognitive performance is greater in synucleinopathy than in amyloidopathy.

  4. Regulation of Substantia Nigra Pars Reticulata GABAergic Neuron Activity by H2O2 via Flufenamic Acid-Sensitive Channels and KATP Channels

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    Lee, Christian R.; Witkovsky, Paul; Rice, Margaret E.

    2011-01-01

    Substantia nigra pars reticulata (SNr) GABAergic neurons are key output neurons of the basal ganglia. Given the role of these neurons in motor control, it is important to understand factors that regulate their firing rate and pattern. One potential regulator is hydrogen peroxide (H2O2), a reactive oxygen species that is increasingly recognized as a neuromodulator. We used whole-cell current clamp recordings of SNr GABAergic neurons in guinea-pig midbrain slices to determine how H2O2 affects the activity of these neurons and to explore the classes of ion channels underlying those effects. Elevation of H2O2 levels caused an increase in the spontaneous firing rate of SNr GABAergic neurons, whether by application of exogenous H2O2 or amplification of endogenous H2O2 through inhibition of glutathione peroxidase with mercaptosuccinate. This effect was reversed by flufenamic acid (FFA), implicating transient receptor potential (TRP) channels. Conversely, depletion of endogenous H2O2 by catalase, a peroxidase enzyme, decreased spontaneous firing rate and firing precision of SNr neurons, demonstrating tonic control of firing rate by H2O2. Elevation of H2O2 in the presence of FFA revealed an inhibition of tonic firing that was prevented by blockade of ATP-sensitive K+ (KATP) channels with glibenclamide. In contrast to guinea-pig SNr neurons, the dominant effect of H2O2 elevation in mouse SNr GABAergic neurons was hyperpolarization, indicating a species difference in H2O2-dependent regulation. Thus, H2O2 is an endogenous modulator of SNr GABAergic neurons, acting primarily through presumed TRP channels in guinea-pig SNr, with additional modulation via KATP channels to regulate SNr output. PMID:21503158

  5. 3D neuromelanin-sensitive magnetic resonance imaging with semi-automated volume measurement of the substantia nigra pars compacta for diagnosis of Parkinson's disease

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    Ogisu, Kimihiro; Shirato, Hiroki [Hokkaido University Graduate School of Medicine, Department of Radiology, Hokkaido (Japan); Kudo, Kohsuke; Sasaki, Makoto [Iwate Medical University, Division of Ultrahigh Field MRI, Iwate (Japan); Sakushima, Ken; Yabe, Ichiro; Sasaki, Hidenao [Hokkaido University Hospital, Department of Neurology, Hokkaido (Japan); Terae, Satoshi; Nakanishi, Mitsuhiro [Hokkaido University Hospital, Department of Radiology, Hokkaido (Japan)

    2013-06-15

    Neuromelanin-sensitive MRI has been reported to be used in the diagnosis of Parkinson's disease (PD), which results from loss of dopamine-producing cells in the substantia nigra pars compacta (SNc). In this study, we aimed to apply a 3D turbo field echo (TFE) sequence for neuromelanin-sensitive MRI and to evaluate the diagnostic performance of semi-automated method for measurement of SNc volume in patients with PD. We examined 18 PD patients and 27 healthy volunteers (control subjects). A 3D TFE technique with off-resonance magnetization transfer pulse was used for neuromelanin-sensitive MRI on a 3T scanner. The SNc volume was semi-automatically measured using a region-growing technique at various thresholds (ranging from 1.66 to 2.48), with the signals measured relative to that for the superior cerebellar peduncle. Receiver operating characteristic (ROC) analysis was performed at all thresholds. Intra-rater reproducibility was evaluated by intraclass correlation coefficient (ICC). The average SNc volume in the PD group was significantly smaller than that in the control group at all the thresholds (P < 0.01, student t test). At higher thresholds (>2.0), the area under the curve of ROC (Az) increased (0.88). In addition, we observed balanced sensitivity and specificity (0.83 and 0.85, respectively). At lower thresholds, sensitivity tended to increase but specificity reduced in comparison with that at higher thresholds. ICC was larger than 0.9 when the threshold was over 1.86. Our method can distinguish the PD group from the control group with high sensitivity and specificity, especially for early stage of PD. (orig.)

  6. Neuromelanin-related contrast in the substantia nigra semiquantitatively evaluated by magnetic resonance imaging at 3T. Comparison between normal aging and Parkinson disease

    International Nuclear Information System (INIS)

    Tanaka, Makoto; Aihara, Yuko; Ikeda, Sachie; Aihara, Yoshiaki

    2011-01-01

    Fast spin-echo (FSE) T 1 -weighted magnetic resonance imaging (MRI) at 3T, which was optimized to detect neuromelanin-related contrast (NRC), was applied to quantitative estimation of signal alterations in the substantia nigra pars compacta (SNc) of 72 normal volunteers and 59 patients with Parkinson disease (PD). We examined relationship between NRC in SNc and clinical parameters. The NRC showed significant positive correlation with normal aging and was slightly but significantly higher in women than in men. Significant reduction in the NRC was found in PD as compared with 59 age- and sex-matched normal volunteers. The NRC in PD was negatively and significantly correlated with duration of illness and disease severity assessed by unified Parkinoson's disease rating scale (UPDRS) and Hoehn and Yahr stage. Significant reduction of the NRC was demonstrated in patients with visual hallucinations as compare with patients without the symptoms. Rapid eye movement (REM) sleep behavior disorder also contributed reduction of NRC although it did more mildly than visual hallucination. Anosmia or hyposmia had no statistical relationship with the amount of NRC in PD. The overall visual inspection indicated that the reduction of the NRC in PD should start at the ventrolateral portion of SNc and advance medially. Additionally, we studied dementia with Lewy body disease (DLB). The NRC was reduced more significantly in DLB patients with PD symptoms than in those without them who also showed a significant reduction compared with normal controls. Quantification and distribution of the NRC obtained by 3T MRI was well correlated with pathological findings reported previously and clinical parameters in this study. Visualization and quantification of the NRC provide some parts of clinical and diagnostic information about pathologic condition of SNc. (author)

  7. Pool size ratio of the substantia nigra in Parkinson's disease derived from two different quantitative magnetization transfer approaches

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    Trujillo, Paula [Department of Neuroradiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI (Italy); Vanderbilt University Medical Center, Department of Neurology, Nashville, TN (United States); Summers, Paul E.; Costa, Antonella [Department of Neuroradiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI (Italy); Smith, Alex K. [University of Oxford, Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neuroscience, Oxford (United Kingdom); Smith, Seth A. [Vanderbilt University Institute of Imaging Science, Nashville, TN (United States); Vanderbilt University, Department of Biomedical Engineering, Nashville, TN (United States); Mainardi, Luca T.; Cerutti, Sergio [Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, MI (Italy); Claassen, Daniel O. [Vanderbilt University Medical Center, Department of Neurology, Nashville, TN (United States)

    2017-12-15

    We sought to measure quantitative magnetization transfer (qMT) properties of the substantia nigra pars compacta (SNc) in patients with Parkinson's disease (PD) and healthy controls (HCs) using a full qMT analysis and determine whether a rapid single-point measurement yields equivalent results for pool size ratio (PSR). Sixteen different MT-prepared MRI scans were obtained at 3 T from 16 PD patients and eight HCs, along with B1, B0, and relaxation time maps. Maps of PSR, free and macromolecular pool transverse relaxation times (T{sub 2}{sup f}, T{sub 2}{sup m}) and rate of MT exchange between pools (k{sub mf}) were generated using a full qMT model. PSR maps were also generated using a single-point qMT model requiring just two MT-prepared images. qMT parameter values of the SNc, red nucleus, cerebral crus, and gray matter were compared between groups and methods. PSR of the SNc was the only qMT parameter to differ significantly between groups (p < 0.05). PSR measured via single-point analysis was less variable than with the full MT model, provided slightly better differentiation of PD patients from HCs (area under curve 0.77 vs. 0.75) with sensitivity of 0.75 and specificity of 0.87, and was better than transverse relaxation time in distinguishing PD patients from HCs (area under curve 0.71, sensitivity 0.87, and specificity 0.50). The increased PSR observed in the SNc of PD patients may provide a novel biomarker of PD, possibly associated with an increased macromolecular content. Single-point PSR mapping with reduced variability and shorter scan times relative to the full qMT model appears clinically feasible. (orig.)

  8. An HPLC tracing of the enhancer regulation in selected discrete brain areas of food-deprived rats.

    Science.gov (United States)

    Miklya, I; Knoll, B; Knoll, J

    2003-05-09

    The recent discovery of the enhancer regulation in the mammalian brain brought a different perspective to the brain-organized realization of goal-oriented behavior, which is the quintessence of plastic behavioral descriptions such as drive or motivation. According to this new approach, 'drive' means that special endogenous enhancer substances enhance the impulse-propagation-mediated release of transmitters in a proper population of enhancer-sensitive neurons, and keep these neurons in the state of enhanced excitability until the goal is reached. However, to reach any goal needs the participation of the catecholaminergic machinery, the engine of the brain. We developed a method to detect the specific enhancer effect of synthetic enhancer substances [(-)-deprenyl, (-)-PPAP, (-)-BPAP] by measuring the release of transmitters from freshly isolated selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus, raphe) by the aid of HPLC with electrochemical detection. To test the validity of the working hypothesis that in any form of goal-seeking behavior the catecholaminergic and serotonergic neurons work on a higher activity level, we compared the amount of norepinephrine, dopamine, and serotonin released from selected discrete brain areas isolated from the brain of sated and food-deprived rats. Rats were deprived of food for 48 and 72 hours, respectively, and the state of excitability of their catecholaminergic and serotonergic neurons in comparison to that of sated rats was measured. We tested the orienting-searching reflex activity of the rats in a special open field, isolated thereafter selected discrete brain areas and measured the release of norepinephrine, dopamine, and serotonin from the proper tissue samples into the organ bath. The orienting-searching reflex activity of the rats increased proportionally to the time elapsed from the last feed and the amount of dopamine released from the striatum, substantia nigra and

  9. Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

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    Adel Jungling

    2017-02-01

    Full Text Available Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD. The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

  10. Enhanced glutamate, IP3 and cAMP activity in the cerebral cortex of Unilateral 6-hydroxydopamine induced Parkinson's rats: Effect of 5-HT, GABA and bone marrow cell supplementation

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    Romeo Chinthu

    2011-01-01

    Full Text Available Abstract Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in Bmax (P

  11. Usefulness of Cardiac MIBG Scintigraphy, Olfactory Testing and Substantia Nigra Hyperechogenicity as Additional Diagnostic Markers for Distinguishing between Parkinson's Disease and Atypical Parkinsonian Syndromes.

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    Hiroaki Fujita

    Full Text Available We aimed to evaluate the utility of the combined use of cardiac 123I-metaiodobenzylguanidine (MIBG scintigraphy, olfactory testing, and substantia nigra (SN hyperechogenicity on transcranial sonography (TCS in differentiating Parkinson's disease (PD from atypical parkinsonian syndromes (APSs, such as multiple system atrophy (MSA and progressive supranuclear palsy (PSP.Cardiac MIBG scintigraphy, card-type odor identification testing (Open Essence (OE, Wako, Japan, and TCS were performed with 101 patients with PD and 38 patients with APSs (MSA and PSP. Receiver operating characteristic (ROC curve analysis was used to assess the sensitivity and specificity of these batteries for diagnosing PD from APSs. The diagnostic accuracy of the three tests was also assessed among patients at the early disease stage (drug-naïve patients with a disease duration of 3 years or less.In differentiating PD from APSs, the area under the ROC curve was 0.74 (95% CI, 0.65-0.83, 0.8 (95% CI, 0.73-0.87, and 0.75 (95% CI, 0.67-0.82 for TCS, cardiac MIBG scintigraphy, and olfactory testing, respectively. The diagnostic sensitivity and specificity were 53.1% and 91.7%, respectively, for TCS, 70.3% and 86.8%, respectively, for cardiac MIBG scintigraphy, 58.4% and 76.3%, respectively, for OE. Among early-stage patients, sensitivity and specificity were 50.0% and 93.8%, respectively, for TCS, 57.1% and 87.5%, respectively, for cardiac MIBG scintigraphy, and 54.8% and 79.2%, respectively, for OE. At least one positive result from 3 tests improved sensitivity (86.1% but decreased specificity (63.2%. In contrast, at least 2 positive results from 3 tests had good discrimination for both early-stage patients (50.0% sensitivity and 93.8% specificity and patients overall (57.8% sensitivity and 95.8% specificity. Positive results for all 3 tests yielded 100% specificity but low sensitivity (25%.At least 2 positive results from among TCS, cardiac MIBG scintigraphy, and olfactory

  12. Duration-dependence of the effect of treadmill exercise on hyperactivity in attention deficit hyperactivity disorder rats.

    Science.gov (United States)

    Ji, Eun-Sang; Kim, Chang-Ju; Park, Jun Heon; Bahn, Geon Ho

    2014-04-01

    Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder, and its symptoms are hyperactivity and deficits in learning and memory. Physical exercise increases dopamine synthesis and neuronal activity in various brain regions. In the present study, we investigate the duration-dependence of the treadmill exercise on hyperactivity in relation with dopamine expression in ADHD. Spontaneously hypertensive rats were used for the ADHD rats and Wistar-Kyoto rats were used for the control rats. The rats in the exercise groups were forced to run on a treadmill for 10 min, 30 min, and 60 min once daily for 28 consecutive days. For this experiment, open field test and immunohistochemistry for tyrosine hydroxylase were conducted. The present results revealed that ADHD rats showed hyperactivity, and tyrosine hydroxylase expression in the striatum and substantia nigra were decreased in ADHD rats. Treadmill exercise alleviated hyperactivity and also increased TH expression in ADHD rats. Treadmill exercise for 30 min per day showed most potent suppressing effect on hyperactivity, and this dose of treadmill exercise also most potently inhibited tyrosine hydroxylase expression. The present study suggests that treadmill exercise for 30 min once a day is the most effective therapeutic intervention for ADHD patients.

  13. Comparative studies of D2 receptors and brain perfusion in hemi-parkinsonism rats

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    2000-01-01

    The relationship between dopamine D 2 receptors and brain perfusion in hemi-parkinsonism rats was studied. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra (SN) and ventral tegmental area (VTA), apomorphine (Apo) which could induced the successful model rat rotates toward the intact side was used to select the rats, 125 I-IBZM ex-vivo autoradiography analysis and 99m Tc-HM-PAO regional cerebral biodistribution were used to evaluate D 2 receptors and cerebral blood flow. The HPLC-ECD were used to measure striatum DA and its metabolites content. The lesioned side striatum DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (p 0.05). These results indicated that in the 6-OH-DA lesioned side DA content decreased significantly and an up-regulation of striatum D 2 receptor binding sites was induced in hemi-parkinsonism rats, which showed good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-parkinsonism

  14. Comparative studies of D2 receptors and cerebral blood flow in hemi-Parkinsonism rats

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    2000-01-01

    Objective: To study the relationship between dopamine D 2 receptors and cerebral blood flow in hemi-Parkinsonism rats. Methods: Hemi-Parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat to rotate toward the intact side was used to select the rat models, 125 I-IBZM in vivo autoradiography and 99 Tc m -HMPAO regional cerebral biodistribution analysis were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD was used to measure striatum DA and its metabolite content . Results: the lesioned side striatum DA and its metabolites homovanillic acid (HVA) 3,4-dihyroxy-phenylacetic acid (DOPAC) reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-Parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (P 0.05). Conclusions: the 6-OH-DA lesioned side DA content decreased significantly and thus induced a compensative up-regulation of striatum D 2 receptor binding sites in hemi-Parkinsonism rats, which show good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-Parkinsonism

  15. Neuroprotective effect of quercetin in a model of Parkinson’s disease in rat: A histochemical analysis

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    Mehdi Mehdizadeh

    2009-01-01

    Full Text Available AbstractIntroduction: Parkinson's disease (PD is a neuropathological disorder involving the degeneration of dopaminergic neurons in the substantia nigra, with the subsequent loss of their terminals in the striatum. Quercetin, a natural flavonoid, is a strong antioxidant and radical scavenger. Therefore, its neuroprotective effect in a model of Parkinson’s disease in rat was evaluated.Methods: For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA-lesioned rats were pretreated with quercetin (20 mg/kg; i.p. 1 hour before surgery and treated once a day for one month. Nissl-stained neurons of substantia nigra pars compacta (SNC were counted. Results: Number of Nissl-stained neurons in left side of SNC of lesion group was lower relative to sham-operated group (p<0.005 and it was higher in quercetin-treated lesion group as compared to untreated lesion group (p<0.01.Discussion: Flavonoid quercetin administration for one month could protect the neurons of SNC against 6-OHDA toxicity. 

  16. Neuroprotective effect of quercetin in a model of Parkinson’s disease in rat: A histochemical analysis

    Directory of Open Access Journals (Sweden)

    Mehdi Mehdizadeh

    2009-01-01

    Full Text Available AbstractIntroduction: Parkinson's disease (PD is a neuropathological disorder involving the degeneration of dopaminergic neurons in the substantia nigra, with the subsequent loss of their terminals in the striatum. Quercetin, a natural flavonoid, is a strong antioxidant and radical scavenger. Therefore, its neuroprotective effect in a model of Parkinson’s disease in rat was evaluated.Methods: For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA-lesioned rats were pretreated with quercetin (20 mg/kg i.p. 1 hour before surgery and treated once a day for one month. Nissl-stained neurons of substantia nigra pars compacta (SNC were counted. Results: Number of Nissl-stained neurons in left side of SNC of lesion group was lower relative to sham-operated group (p<0.005 and it was higher in quercetin-treated lesion group as compared to untreated lesion group (p<0.01.Discussion: Flavonoid quercetin administration for one month could protect the neurons of SNC against 6-OHDA toxicity.

  17. Photobiomodulation Suppresses Alpha-Synuclein-Induced Toxicity in an AAV-Based Rat Genetic Model of Parkinson's Disease.

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    Abid Oueslati

    Full Text Available Converging lines of evidence indicate that near-infrared light treatment, also known as photobiomodulation (PBM, may exert beneficial effects and protect against cellular toxicity and degeneration in several animal models of human pathologies, including neurodegenerative disorders. In the present study, we report that chronic PMB treatment mitigates dopaminergic loss induced by unilateral overexpression of human α-synuclein (α-syn in the substantia nigra of an AAV-based rat genetic model of Parkinson's disease (PD. In this model, daily exposure of both sides of the rat's head to 808-nm near-infrared light for 28 consecutive days alleviated α-syn-induced motor impairment, as assessed using the cylinder test. This treatment also significantly reduced dopaminergic neuronal loss in the injected substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum. These beneficial effects were sustained for at least 6 weeks after discontinuing the treatment. Together, our data point to PBM as a possible therapeutic strategy for the treatment of PD and other related synucleinopathies.

  18. Iron and cell death in Parkinson's disease: a nuclear microscopic study into iron-rich granules in the parkinsonian substantia nigra of primate models

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    Thong, P.S.P.; Watt, F. E-mail: phywattf@nus.edu.sg; Ponraj, D.; Leong, S.K.; He, Y.; Lee, T.K.Y

    1999-09-02

    Parkinson's disease is a degenerative brain disease characterised by a loss of cells in the substantia nigra (SN) region of the brain and accompanying biochemical changes such as inhibition of mitochondrial function, increased iron concentrations and decreased glutathione levels in the parkinsonian SN. Though the aetiology of the disease is still unknown, the observed biochemical changes point to the involvement of oxidative stress. In particular, iron is suspected to play a role by promoting free radical production, leading to oxidative stress and cell death. The increase in iron in the parkinsonian SN has been confirmed by several research groups, both in human post-mortem brains and in brain tissue from parkinsonian animal models. However, the question remains as to whether the observed increase in iron is a cause or a consequence of the SN cell death process. Our previous study using unilaterally 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-lesioned monkeys in a time sequence experiment has shown that the increase in bulk iron concentrations follow rather than precede dopaminergic cell death. However, changes in the localised iron concentrations, which may play a more direct role in SN cell death, may not be reflected at the bulk level. Indeed, we have observed iron-rich granules in parkinsonian SNs. From this time sequence study into the iron content of iron-rich granules in the SNs of an untreated control and unilaterally MPTP-lesioned parkinsonian models, we present the following observations: (1) Iron-rich granules are found in both control and parkinsonian SNs and are variable in size and iron content in any one model. (2) These iron-rich granules may be associated with neuromelanin granules found in the SN and are known to accumulate transition metal ions such as iron. (3) The early onset of bulk SN cell loss (35%) was accompanied by a significant elevation of iron in granules found in the MPTP-injected SN compared to the contra-lateral SN

  19. High affinity [3H]glibenclamide binding sites in rat neuronal and cardiac tissue: Localization and developmental characteristics

    International Nuclear Information System (INIS)

    Miller, J.A.; Velayo, N.L.; Dage, R.C.; Rampe, D.

    1991-01-01

    We examined the binding of the antidiabetic sulfonylurea [3H] glibenclamide to rat brain and heart membranes. High affinity binding was observed in adult rat forebrain (Kd = 137.3 pM, maximal binding site density = 91.8 fmol/mg of protein) and ventricle (Kd = 77.1 pM, maximal binding site density = 65.1 fmol/mg of protein). Binding site density increased approximately 250% in forebrain membranes during postnatal development but was constant in ventricular membranes. Quantitative autoradiography was used to examine the regional distribution of [3H] glibenclamide binding sites in sections from rat brain, spinal cord and heart. The greatest density of binding in adult brain was found in the substantia nigra and globus pallidus, whereas the other areas displayed heterogenous binding. In agreement with the membrane binding studies, 1-day-old rat brain had significantly fewer [3H]glibenclamide binding sites than adult brain. Additionally, the pattern of distribution of these sites was qualitatively different from that of the adult. In adult rat spinal cord, moderate binding densities were observed in spinal cord gray and displayed a rostral to caudal gradient. In adult rat heart, moderate binding densities were observed and the sites were distributed homogeneously. In conclusion, significant development of [3H]glibenclamide binding sites was seen in the brain but not the heart during postnatal maturation. Furthermore, a heterogeneous distribution of binding sites was observed in both the brain and spinal cord of adult rats

  20. The effects of apomorphine upon local cerebral glucose utilization in conscious rats and in rats anesthetized with chloral hydrate

    Energy Technology Data Exchange (ETDEWEB)

    Grome, J J; McCulloch, J

    1983-02-01

    The effects of the dopaminergic agonist apomorphine (1 mg . kg-1 i.v.) upon local cerebral glucose utilization in 43 anatomically discrete regions of the CNS were examined in conscious, lightly restrained rats and in rats anesthetized with chloral hydrate by means of the quantitative autoradiographic (/sup 14/C)2-deoxyglucose technique. In animals anesthetized with chloral hydrate, glucose utilization was reduced throughout all regions of the CNS from the levels observed in conscious animals, although the magnitude of the reductions in glucose use displayed considerable regional heterogeneity. With chloral hydrate anesthesia, the proportionately most marked reductions in glucose use (by 40-60% from conscious levels) were noted in primary auditory nuclei, thalmaic relay nuclei, and neocortex, and the least pronounced reductions in glucose use (by 15-25% from conscious levels) were observed in limbic areas, some motor relay nuclei, and white matter. In conscious, lightly restrained rats, the administration of apomorphine (1 mg . kg-1) effected significant increased in glucose utilization in 15 regions of the CNS (e.g., subthalamic nucleus, ventral thalamic nucleus, rostral neocortex, substantia nigra, pars reticulata), and significant reductions in glucose utilization in two regions of the CNS (lateral habenular nucleus and anterior cingulate cortex).

  1. Urocortin, a CRF-like peptide, restores key indicators of damage in the substantia nigra in a neuroinflammatory model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Biggs Christopher S

    2007-07-01

    Full Text Available Abstract We have recently observed that the corticotrophin releasing hormone (CRF related peptide urocortin (UCN reverses key features of nigrostriatal damage in the hemiparkinsonian 6-hydroxydopamine lesioned rat. Here we have studied whether similar effects are also evident in the lipopolysaccaride (LPS neuroinflammatory paradigm of Parkinson's disease (PD. To do this we have measured restoration of normal motor behaviour, retention of nigral dopamine (DA and also tyrosine hydroxylase (TH activity. Fourteen days following intranigral injections of LPS and UCN, rats showed only modest circling after DA receptor stimulation with apomorphine, in contrast to those given LPS and vehicle where circling was pronounced. In separate experiments, rats received UCN seven days following LPS, and here apomorphine challenge caused near identical circling intensity to those that received LPS and UCN concomitantly. In a similar and consistent manner with the preservation of motor function, UCN 'protected' the nigra from both DA depletion and loss of TH activity, indicating preservation of DA cells. The effects of UCN were antagonised by the non-selective CRF receptor antagonist α-helical CRF and were not replicated by the selective CRF2 ligand UCN III. This suggests that UCN is acting via CRF1 receptors, which have been shown to be anti-inflammatory in the periphery. Our data therefore indicate that UCN is capable of maintaining adequate nigrostriatal function in vivo, via CRF1 receptors following a neuro-inflammatory challenge. This has potential therapeutic implications in PD.

  2. Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.

    Directory of Open Access Journals (Sweden)

    Anna Kubesova

    Full Text Available Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and Alzheimer's disease. The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin, their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases--glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders.

  3. Cholinergic, opioid and glycine receptor binding sites localized in human spinal cord by in vitro autoradiography

    International Nuclear Information System (INIS)

    Gillberg, P.-G.; Aquilonius, S.-M.

    1985-01-01

    Binding sites for the receptor ligands 3 H-quinuclidinylbenzilate, 3 H-alpha-bungarotoxin ( 3 H-alpha-Btx), 3 H-etorphine and 3 H-strychnine were localized autoradiographically at cervical, thoracic and lumbar levels of spinal cords from post-mortem human control subjects and subjects with amyotrophic lateral sclerosis (ALS). The highest densities of muscarinic binding sites were found in the motor neuron areas and in the substantia gelatinosa, while the grey matter binding was very low within Clarke's column. Both 3 H-alpha-Btx and opioid receptor binding sites were numerous within the substantia gelatinosa, while glycine receptor binding sites were more uniformly distribute within the spinal grey matter. In ALS cases, muscarinic receptor binding sites were markedly reduced in motor neuron areas and slightly reduced in the dorsal horn, while the other binding sites studied were relatively unchanged. (author)

  4. Effects of Melatonin on the Cerebellum of Infant Rat Following Kaolin-Induced Hydrocephalus: a Histochemical and Immunohistochemical Study.

    Science.gov (United States)

    Uyanıkgil, Yiğit; Turgut, Mehmet; Baka, Meral

    2017-02-01

    Hydrocephalus is a developmental disorder causing abnormally collected cerebrospinal fluid within the cerebral ventricles. It leads to bigger skulls and many dysfunctions related to the nervous system. Here, we addressed whether exogenous melatonin administration could reverse the clinical features of kaolin-induced hydrocephalus in infantile rats. A controlled double-blinded study was conducted in 2-week-old 45 Wistar albino rats, which were divided into three groups: Group A, the control group, received intracisternal sham injection with solely the needle insertion; group B, the hydrocephalus group, was treated with isotonic NaCl after kaolin injection; and group C, the hydrocephalus + melatonin group, was given i.p. exogenous melatonin at a dose of 0.5 mg/100 g body weight after kaolin injection. Histological and immunohistochemical analyses were performed after the induction of hydrocephalus and melatonin administration. Glial fibrillary acidic protein was stained by immunohistochemical method. TUNEL method was used to define and quantitate apoptosis in the cerebellar tissues. Statistical analysis was performed by nonparametric Kruskal-Wallis H test, and once significance was determined among means, post hoc pairwise comparisons were carried out using Mann-Whitney U test. We found that melatonin administration significantly ameliorated ratio of substantia grisea area/substantia alba area in the cerebellum of infantile rats. Histologically, there was a significant reduction in the number of cerebellar apoptotic cells after the hydrocephalus induced by kaolin (P cerebellum were reversed by systemic melatonin administration in infantile rats with kaolin-induced hydrocephalus. Nevertheless, further studies are needed to suggest melatonin as a candidate protective drug in children with hydrocephalus.

  5. Topographic and functional neuroanatomical study of GABAergic disinhibitory striatum-nigral inputs and inhibitory nigrocollicular pathways: neural hodology recruiting the substantia nigra, pars reticulata, for the modulation of the neural activity in the inferior colliculus involved with panic-like emotions.

    Science.gov (United States)

    Castellan-Baldan, Lissandra; da Costa Kawasaki, Mateus; Ribeiro, Sandro José; Calvo, Fabrício; Corrêa, Vani Maria Alves; Coimbra, Norberto Cysne

    2006-08-01

    Considering the influence of the substantia nigra on mesencephalic neurons involved with fear-induced reactions organized in rostral aspects of the dorsal midbrain, the present work investigated the topographical and functional neuroanatomy of similar influence on caudal division of the corpora quadrigemina, addressing: (a) the neural hodology connecting the neostriatum, the substantia nigra, periaqueductal gray matter and inferior colliculus (IC) neural networks; (b) the influence of the inhibitory neostriatonigral-nigrocollicular GABAergic links on the control of the defensive behavior organized in the IC. The effects of the increase or decrease of activity of nigrocollicular inputs on defensive responses elicited by either electrical or chemical stimulation of the IC were also determined. Electrolytic or chemical lesions of the substantia nigra, pars reticulata (SNpr), decreased the freezing and escape behaviors thresholds elicited by electrical stimulation of the IC, and increased the behavioral responses evoked by the GABAA blockade in the same sites of the mesencephalic tectum (MT) electrically stimulated. These findings were corroborated by similar effects caused by microinjections of the GABAA-receptor agonist muscimol in the SNpr, followed by electrical and chemical stimulations of the IC. The GABAA blockade in the SNpr caused a significant increase in the defensive behavior thresholds elicited by electrical stimulation of the IC and a decrease in the mean incidence of panic-like responses induced by microinjections of bicuculline in the mesencephalic tectum (inferior colliculus). These findings suggest that the substantia nigra receives GABAergic inputs that modulate local and also inhibitory GABAergic outputs toward the IC. In fact, neurotracing experiments with fast blue and iontophoretic microinjections of biotinylated dextran amine either into the inferior colliculus or in the reticular division of the substantia nigra demonstrated a neural link

  6. Neuronal network disturbance after focal ischemia in rats

    International Nuclear Information System (INIS)

    Kataoka, K.; Hayakawa, T.; Yamada, K.; Mushiroi, T.; Kuroda, R.; Mogami, H.

    1989-01-01

    We studied functional disturbances following left middle cerebral artery occlusion in rats. Neuronal function was evaluated by [14C]2-deoxyglucose autoradiography 1 day after occlusion. We analyzed the mechanisms of change in glucose utilization outside the infarct using Fink-Heimer silver impregnation, axonal transport of wheat germ agglutinin-conjugated-horseradish peroxidase, and succinate dehydrogenase histochemistry. One day after occlusion, glucose utilization was remarkably reduced in the areas surrounding the infarct. There were many silver grains indicating degeneration of the synaptic terminals in the cortical areas surrounding the infarct and the ipsilateral cingulate cortex. Moreover, in the left thalamus where the left middle cerebral artery supplied no blood, glucose utilization significantly decreased compared with sham-operated rats. In the left thalamus, massive silver staining of degenerated synaptic terminals and decreases in succinate dehydrogenase activity were observed 4 and 5 days after occlusion. The absence of succinate dehydrogenase staining may reflect early changes in retrograde degeneration of thalamic neurons after ischemic injury of the thalamocortical pathway. Terminal degeneration even affected areas remote from the infarct: there were silver grains in the contralateral hemisphere transcallosally connected to the infarct and in the ipsilateral substantia nigra. Axonal transport study showed disruption of the corticospinal tract by subcortical ischemia; the transcallosal pathways in the cortex surrounding the infarct were preserved. The relation between neural function and the neuronal network in the area surrounding the focal cerebral infarct is discussed with regard to ischemic penumbra and diaschisis

  7. Distribution of PDE8A in the nervous system of the Sprague-Dawley rat

    DEFF Research Database (Denmark)

    Kruse, Lars Schack; Møller, Morten; Kruuse, Christina

    2011-01-01

    in the brain of adult male Sprague-Dawley rats and in the trigeminal ganglion. PDE8A was confined to neuronal perikaryal cytoplasm and to processes extending from those perikarya. The neurons exhibiting PDE8A-immunoreactivity were widely distributed in the forebrain, brain stem, and cerebellum. Strongly...... immunoreactive neurons were located in the olfactory bulb, the septal area, zona incerta, and reticular nucleus of the thalamus. Less immunoreactivity was seen in the hippocampus and cerebral cortex. Intense staining was detected in both the substantia nigra and the sensory trigeminal nucleus. In cerebellum PDE8....... The localization of the cAMP degrading PDE8A may indicate a role for PDE8A in cAMP signaling related to pain transmission, motor function, cognition and olfaction....

  8. A Single Neonatal Exposure to BMAA in a Rat Model Produces Neuropathology Consistent with Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Laura Louise Scott

    2017-12-01

    Full Text Available Although cyanobacterial β-N-methylamino-l-alanine (BMAA has been implicated in the development of Alzheimer’s Disease (AD, Parkinson’s Disease (PD and Amyotrophic Lateral Sclerosis (ALS, no BMAA animal model has reproduced all the neuropathology typically associated with these neurodegenerative diseases. We present here a neonatal BMAA model that causes β-amyloid deposition, neurofibrillary tangles of hyper-phosphorylated tau, TDP-43 inclusions, Lewy bodies, microbleeds and microgliosis as well as severe neuronal loss in the hippocampus, striatum, substantia nigra pars compacta, and ventral horn of the spinal cord in rats following a single BMAA exposure. We also report here that BMAA exposure on particularly PND3, but also PND4 and 5, the critical period of neurogenesis in the rodent brain, is substantially more toxic than exposure to BMAA on G14, PND6, 7 and 10 which suggests that BMAA could potentially interfere with neonatal neurogenesis in rats. The observed selective toxicity of BMAA during neurogenesis and, in particular, the observed pattern of neuronal loss observed in BMAA-exposed rats suggest that BMAA elicits its effect by altering dopamine and/or serotonin signaling in rats.

  9. Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats.

    Science.gov (United States)

    Baxter, Mark G; Bucci, David J; Gorman, Linda K; Wiley, Ronald G; Gallagher, Michela

    2013-10-01

    Male Long-Evans rats were given injections of either 192 IgG-saporin, an apparently selective toxin for basal forebrain cholinergic neurons (LES), or vehicle (CON) into either the medial septum and vertical limb of the diagonal band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and substantia innominata (nBM/SI). Place discrimination in the Morris water maze assessed spatial learning, and a trial-unique matching-to-place task in the water maze assessed memory for place information over varying delays. MS/VDB-LES and nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the place discrimination, but were mildly impaired relative to CON rats in performance of the memory task even at the shortest delay, suggesting a nonmnemonic deficit. These results contrast with effects of less selective lesions, which have been taken to support a role for basal forebrain cholinergic neurons in learning and memory. 2013 APA, all rights reserved

  10. Role of L-thyroxin in counteracting rotenone induced neurotoxicity in rats.

    Science.gov (United States)

    Salama, Mohamed; Helmy, Basem; El-Gamal, Mohamed; Reda, Amr; Ellaithy, Amr; Tantawy, Dina; Mohamed, Mie; El-Gamal, Aya; Sheashaa, Hussein; Sobh, Mohamed

    2013-03-01

    A key feature of Parkinson's disease is the dopaminergic neuronal cell loss in the substantia nigra pars compacta. Many triggering pathways have been incriminated in the pathogenesis of this disease including inflammation, oxidative stress, excitotoxicity and apoptosis. Thyroid hormone is an essential agent for the growth and maturation of neurons; moreover, it has variable mechanisms for neuroprotection. So, we tested the efficacy of (L)-thyroxin as a neuroprotectant in rotenone model of Parkinson's disease in rats. Thirty Sprague Dawley rats aged 3 months were divided into 3 equal groups. The first received daily intraperitoneal injections of 0.5% carboxymethyl cellulose (CMC) 3 mL/Kg. The second group received rotenone suspended in 0.5% CMC intraperitoneally at a dose of 3 mg/kg, daily. The third group received the same rotenone regimen subcutaneous l-thyroxine at a dose of 7.5 μg daily. All animals were evaluated regarding locomotor disturbance through blinded investigator who monitored akinesia, catalepsy, tremors and performance in open field test. After 35 days the animals were sacrificed and their brains were immunostained against anti-tyrosine hydroxylase and iba-1. Photomicrographs for coronal sections of the substantia nigra and striatum were taken and analyzed using image J software to evaluate cell count in SNpc and striatal fibers density and number of microglia in the nigrostriatal system. The results were then analyzed statistically. Results showed selective protective effects of thyroxin against rotenone induced neurotoxicity in striatum, however, failed to exert similar protection on SN. Moreover, microglial elevated number in nigrostriatal system that was induced by rotenone injections was diminished selectively in striatum only in the l-thyroxin treated group. One of the possible mechanisms deduced from this work was the selective regulation of microglia in striatal tissues. Thus, this study provides an insight into thyroxin neuroprotection

  11. Behavioral and neurochemical effects of chronic administration of reserpine and SKF-38393 in rats

    International Nuclear Information System (INIS)

    Neisewander, J.L.; Lucki, I.; McGonigle, P.

    1991-01-01

    Alterations in the density of dopamine receptor subtypes and behaviors mediated by the D1-selective agonist SKF-38393 were examined in rats treated chronically with reserpine, SKF-38393 or the combination of these drugs. Animals received either vehicle or reserpine (1 mg/kg s.c.) on days 1 to 28 and, in addition, half of each of these groups were treated with vehicle and half were treated with SKF-38393 (5-10 mg/kg s.c.) on days 15 to 29. Quantitative autoradiographic measurement of D1 receptors labeled with [ 3 H]SCH-23390 and D2 receptors labeled with [ 3 H]spiroperidol revealed that chronic administration of reserpine increased the density of both receptor subtypes in the nucleus accumbens and caudate-putamen, but not in the substantia nigra. Chronic administration of SKF-38393 alone did not alter D1 receptor density in any of these regions. However, chronic administration of the agonist in reserpinized animals decreased D1 receptor density in the nucleus accumbens, but not in the caudate-putamen or substantia nigra, demonstrating that this partial agonist can selectively down-regulate D1 receptors when endogenous dopaminergic tone is removed. The chronic drug treatments also altered behavioral responses. Chronic administration of SKF-38393 alone produced sensitization of the oral dyskinesia response elicited by a challenge injection of the agonist, but no significant change in the grooming response. Acute administration of SKF-38393 in rats treated with reserpine for 14 days produced stereotypy which was not altered after chronic administration of the agonist. Surprisingly, chronic administration of reserpine alone produced a spontaneous oral dyskinesia, which was blocked dose-dependently by the D2-selective antagonist spiroperidol. These findings are discussed in terms of their relevance to Parkinson's disease and tardive dyskinesia

  12. (3H)-dihydrotestosterone in catecholamine neurons of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence

    International Nuclear Information System (INIS)

    Heritage, A.S.; Stumpf, W.E.; Sar, M.; Grant, L.D.

    1981-01-01

    A combined formaldehyde-induced fluorescence (FIF)-autoradiography procedure was used to determine how and where the androgen, dihydrotestosterone (DHT), is associated with catecholamine systems in the rat brain. With this dual localization method, ( 3 H)-DHT target sites can be visualized in relation to catecholamine perikarya and terminals. In the hindbrain, catecholamine neurons adjacent to the fourth ventricle (group A4), the nucleus (n.) olivaris superior (group A5), the n. parabranchialis medialis (group A7), and in the locus coeruleus (group A6) and subcoeruleal regions, as well as in the substantia grisea centralis, concentrate ( 3 H)-DHT in their nuclei. ( 3 H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following hindbrain regions: n. motorius dorsalis nervi vagi, n. tractus solitarii, n. commissuralis, n. raphe pallidus, n. olivaris inferior, the ventrolateral portion of the substantia grisea centralis, n. cuneiformis, and the ventrolateral reticular formation in the caudal mesencephalon. In the forebrain, ( 3 H)-DHT concentrates in nuclei of catecholamine neurons located in the n. arcuatus and n. periventricularis (group A12). In addition, ( 3 H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following forebrain regions: n. periventricularis rotundocellularis, n. paraventricularis, n. dorsomedialis, n. periventricularis, area retrochiasmatica, n. interstititalis striae terminalis (ventral portion), and n. amygdaloideus centralis. The disclosure of a morphologic association between ( 3 H)-DHT target sites and certain brain catecholamine systems suggests a close functional interdependence between androgens and catecholamines

  13. Electrophysiological and pharmacological evidence for the existence of distinct subpopulations of nigrostriatal dopaminergic neuron in the rat.

    Science.gov (United States)

    Shepard, P D; German, D C

    1988-11-01

    The electrophysiological and pharmacological properties of dopaminergic neurons were systematically examined throughout the anterior-posterior extent of the substantia nigra zona compacta in the rat. Cells were characterized in terms of their (1) firing pattern, (2) firing rate, (3) antidromic response properties, and (4) inhibition in firing rate following dopaminergic agonist administration. These properties were then related to the cell's position within one of four anterior-posterior segments of the nucleus. There were three types of neuronal discharge pattern encountered; irregular, burst and regular. Cells which exhibited different firing patterns exhibited different firing rates and anatomical locations within the substantia nigra zona compacta. All neurons were antidromically activated from the striatum, however, the burst- and regular-firing cells exhibited significantly faster estimated conduction velocities than irregular-firing cells. The irregular-firing cells were most sensitive to dopaminergic autoreceptor agonists whereas the burst-firing cells were most sensitive to an indirect-acting dopaminergic agonist. These experiments provide both electrophysiological and pharmacological evidence to indicate that nigrostriatal dopaminergic neurons are composed of distinct subpopulations which are characterized by their firing pattern.

  14. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Alvarado, M.; Budinger, T.F.; Grossman, R.; Hensley, K.; West, M.S.; Kotake, Y.; Ono, M.; Floyd, R.A.

    2001-12-10

    Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

  15. Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

    Science.gov (United States)

    Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

    2014-12-01

    Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

  16. Selective alterations in cerebral metabolism within the mesocorticolimbic dopaminergic system produced by acute cocaine administration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Porrino, L.J.; Domer, F.R.; Crane, A.M.; Sokoloff, L.

    1988-05-01

    The 2-(/sup 14/C)deoxyglucose method was used to examine the effects of acute intravenous administration of cocaine on local cerebral glucose utilization in rats. These effects were correlated with the effects of cocaine on locomotor activity assessed simultaneously in the same animals. At the lowest dose of cocaine, 0.5 mg/kg (1.47 mumol/kg), alterations in glucose utilization were restricted to the medial prefrontal cortex and nucleus accumbens. Metabolic activity at 1.0 mg/kg (2.9 mumol/kg) was altered in these structures, but in the substantia nigra reticulata and lateral habenula as well. The selectivity of cocaine's effects at low doses demonstrates the particular sensitivity of these structures to cocaine's actions in the brain. In contrast, 5.0 mg/kg (14.7 mumol/kg) produced widespread changes in glucose utilization, particularly in the extrapyramidal system. Only this dose significantly increased locomotor activity above levels in vehicle-treated controls. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, and subthalamic nucleus, and negatively correlated in the lateral habenula.

  17. Differentiated cells derived from fetal neural stem cells improve motor deficits in a rat model of Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Hao Song; Aifang Shen; Chao Chen; Yanming Liu; Yabing Dong; Fabin Han

    2015-01-01

    Objective: Parkinson’s disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

  18. A comparison of substantia nigra T1 hyperintensity in Parkinson's disease dementia, Alzheimer's disease and age-matched controls: Volumetric analysis of neuromelanin imaging

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Won Jin; Park, Ju Yeon; Yun, Won Sung; Jeon, Ji Yeong; Moon, Yeon Sil; Kim, Hee Jin; Han, Seol Heui [Konkuk University School of Medicine, Seoul (Korea, Republic of); Kwak, Ki Chang; Lee, Jong Min [Dept. of Biomedical Engineering, Hanyang University, Seoul (Korea, Republic of)

    2016-09-15

    Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases.

  19. Comparative studies of D2 receptors and cerebral blood flow in hemi-parkinsonism rats

    International Nuclear Information System (INIS)

    Lin, Y.; Lin, X.

    2000-01-01

    To study the relationship between dopamine (DA) D 2 receptors and cerebral blood flow in hemiparkinsonism rats. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat rotates toward the intact side was used to screen that rats, 125 I-IBZM in vivo autoradiography and 99m Tc-HM-PAO regional brain biodistribution were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD were used to measure the concentration of DA and it metabolites homovanillic acid (HVA), 3,4-dehydroxyphenyl acetic acid (DOPAC) in bilateral striatum (ST). The lesioned side ST DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and pseudo-operated control group, ST/cerebellum (CB) 125 I-IBZM uptake ratio was 8.04 ±0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (p 99m Tc 30.1±4.53% enhancement as compared to the intact side, and also show good correlation with 30 min Apo induced rotation numbers (r=0.98), the regional cerebral blood flow study didn't show significant difference between bilateral brain cortex area (p>0.05). The DA content decreased significantly and induced an up-regulation of ST D 2 receptor binding sites in 6-OH-DA lesioned side in hemi-parkinsonism rats, the increased percentage of lesioned-intact side ST/CB 125 I-IBZM uptake ratio showed good correlation with rotation behavior induced by Apo. Compare with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-parkinsonism

  20. Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

    Directory of Open Access Journals (Sweden)

    Dougherty Patrick M

    2009-07-01

    Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

  1. Distribution of corticotropin-releasing factor receptors in primate brain

    International Nuclear Information System (INIS)

    Millan, M.A.; Jacobowitz, D.M.; Hauger, R.L.; Catt, K.J.; Aguilera, G.

    1986-01-01

    The distribution and properties of receptors for corticotropin-releasing factor (CRF) were analyzed in the brain of cynomolgus monkeys. Binding of [ 125 I]tyrosine-labeled ovine CRF to frontal cortex and amygdala membrane-rich fractions was saturable, specific, and time- and temperature-dependent, reaching equilibrium in 30 min at 23 0 C. Scatchard analysis of the binding data indicated one class of high-affinity sites with a K/sub d/ of 1 nM and a concentration of 125 fmol/mg. As in the rat pituitary and brain, CRF receptors in monkey cerebral cortex and amygdala were coupled to adenylate cyclase. Autoradiographic analysis of specific CRF binding in brain sections revealed that the receptors were widely distributed in the cerebral cortex and limbic system. Receptor density was highest in the pars tuberalis of the pituitary and throughout the cerebral cortex, specifically in the prefrontal, frontal, orbital, cingulate, insular, and temporal areas, and in the cerebellar cortex. A low binding density was present in the superior colliculus, locus coeruleus, substantia gelatinosa, preoptic area, septal area, and bed nucleus of the stria terminalis. These data demonstrate that receptors for CRF are present within the primate brain at areas related to the central control of visceral function and behavior, suggesting that brain CRF may serve as a neurotransmitter in the coordination of endocrine and neural mechanisms involved in the response to stress

  2. Proteomic Analysis of Parkin Isoforms Expression in Different Rat Brain Areas.

    Science.gov (United States)

    D'Amico, Agata Grazia; Maugeri, Grazia; Reitano, Rita; Cavallaro, Sebastiano; D'Agata, Velia

    2016-10-01

    PARK2 gene's mutations are related to the familial form of juvenile Parkinsonism, also known as the autosomic recessive juvenile Parkinsonism. This gene encodes for parkin, a 465-amino acid protein. To date, a large number of parkin isoforms, generated by an alternative splicing mechanism, have been described. Currently, Gene Bank lists 27 rat PARK2 transcripts, which matches to 20 exclusive parkin alternative splice variants. Despite the existence of these isoforms, most of the studies carried out so far, have been focused only on the originally cloned parkin. In this work we have analyzed the expression profile of parkin isoforms in some rat brain areas including prefrontal cortex, hippocampus, substantia nigra and cerebellum. To discriminate among these isoforms, we detected their localization through the use of two antibodies that are able to identify different domains of the parkin canonical sequence. Our analysis has revealed that at least fourteen parkin isoforms are expressed in rat brain with a various distribution in the regions analyzed. Our study might help to elucidate the pathophysiological role of these proteins in the central nervous system.

  3. treated rats

    African Journals Online (AJOL)

    aghomotsegin

    2014-01-08

    Jan 8, 2014 ... nucleus, bizarre segmentation; (I) shows hypersegmentation, bizarre segmentation of neutrophils in the shape of ring nucleus with polychromatophilic RBCs. 1998; Muller and Tobin, 1980). The current study shows that rats administered C. edulis hydro-ethanol extract, orally for 28 days, developed anemia, ...

  4. Neurons in the monoaminergic nuclei of the rat and human central nervous system express FA1/dlk

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Meyer, M; Schrøder, Henrik Daa

    2001-01-01

    The gene DLK1 encodes a member of the epidermal growth factor (EGF) superfamily, delta-like (dlk). When exposed in vivo to the action of an unknown protease, this type 1 membrane protein generates a soluble peptide referred to as Fetal antigen 1 (FA1). By acting in juxtacrine as well as paracrine....../autocrine manners, both forms have been shown to be active in the differentiation/proliferation process of various cell types. In adults, FA1/dlk has been demonstrated mainly within (neuro) endocrine tissues. In this study we investigated the presence of FA1/dlk in other parts of the developing and adult rat...... and human CNS. Using immunocytochemistry and in situ hybridization we found that in both species FA1/dlk was expressed in neurons of the Edinger-Westphal's nucleus as well as in substantia nigra, ventral tegmental area (VTA), locus coeruleus and in certain parts of the raphe nuclei....

  5. Autoradiographic localization of glucocorticosteriod binding sites in rat brain after in vivo injection of [3H]RU 28362

    International Nuclear Information System (INIS)

    Sarrieau, Alain; Dussaillant, Monique; Rostene, William

    1988-01-01

    The autoradiographic distribution of glucocorticosteriod binding sites in the brain of adrenalectomized rats was studied following in vivo injection of a potent synthetic glucocorticosteriod agonist [ 3 H]RU 28362. Analysis of the autoradiograms revealed a specific and dense labelling in the pyramidal cell layer of the Ammon's horn and in the granular cell layer of the dentate gyrus of the hippocampus. In the hypothalmus, the labelling was particularly high in the paraventricular nucleus (site of CRF synthesis), the arcuate, periventricular and the supraoptic nuclei as well as in the median eminence. Autoradiograms also revealed the presence of[ 3 H]RU 28362 binding sites in several brain regions including the amygdala, the pineal gland, the entorhinal cortex, the interpeduncular, interfascicular and dorsal raphe nuclei, the central grey and the substantia nigra suggesting possible effects of glucocorticosteriods in these structures (author)

  6. Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.

    Directory of Open Access Journals (Sweden)

    Ying-Zheng Zhao

    Full Text Available Intranasal administration of phospholipid-based gelatin nanoparticles (GNP was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP on hemiparkinsonian rats.The SP-loaded gelatin nanoparticles (SP-GNP were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM. The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH, phosphorylated c-Jun protein (p-c-Jun and Caspase-3 (Cas-3 expressed in substantia nigra (SN region of hemiparkinsonian rats.PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration.With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.

  7. Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

    International Nuclear Information System (INIS)

    See, R.E.; Ellison, G.; Toga, A.W.

    1990-01-01

    Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2([ 3 H]spiperone and [ 3 H]raclopride), dopamine D1([ 3 H]SCH23390), GABA A ([ 3 H]muscimol), benzodiazepine ([ 3 H]RO15-1788), and muscarinic ACh receptors ([ 3 H]QNB). [ 3 H]spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal [ 3 H]raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in [ 3 H]SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in [ 3 H]muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of [ 3 H]QNB and [ 3 H]RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors)

  8. Opioid receptors in midbrain dopaminergic regions of the rat. 1. Mu receptor autoradiography

    International Nuclear Information System (INIS)

    German, D.C.; Speciale, S.G.; Manaye, K.F.; Sadeq, M.

    1993-01-01

    Several lines of evidence indicate that an interaction exists between opioid peptides and midbrain dopaminergic neurons. The purpose of this study was to map and quantify the density of the mu opioid receptor subtype relative to the location of the dopaminergic (DA) neurons in the retrorubral field (nucleus A8), substantia nigra (nucleus A9), and ventral tegmental area and related nuclei (nucleus A10) in the rat. Sections through the rostral-caudal extent of the midbrain were stained with an antibody against tyrosine hydroxylase, as a DA cell marker, and comparable sections were processed for in vitro receptor autoradiography using the mu-selective ligand, 3 H-Tyr-D-Ala-N-MePhe-Gyl-ol enkephalin. In the nucleus A8 region, there were low levels of mu binding. In the rostral portion of nucleus A9, there was prominent mu binding both in the ventral pars compacta, which contains numerous DA neurons, and in regions that correspond to the location of the DA dendrites which project ventrally into the underlying substantia nigra pars reticulata. In the caudal portion of nucleus A9, mu binding was greatest in the substantia nigra pars reticulata, but also in the same region that contains DA neurons. In nucleus A10, mu receptor densities differed depending upon the nucleus A10 subdivision, and the rostral-caudal position in the nucleus. Low receptor densities were observed in rostral portions of the ventral tegmental area and interfascicular nucleus, and there was negligible binding in the parabrachial pigmented nucleus and paranigral nucleus at the level of the interpeduncular nucleus; all regions where there are high densities of DA somata. Mu binding was relatively high in the central linear nucleus, and in the dorsal and medial divisions of the medial terminal nucleus of the accessory optic system, which has been shown to contain DA dendrites. These data indicate that mu opioid receptors are located in certain regions occupied by all three midbrain DA nuclei, but in a

  9. Neuroanatomical patterns of the mu, delta, and kappa opioid receptors of rat brain as determined by quantitative in vitro autoradiography

    International Nuclear Information System (INIS)

    Tempel, A.; Zukin, R.S.

    1987-01-01

    Highly specific radioligands and quantitative autoradiography reveal strikingly different neuroanatomical patterns for the mu, delta, and kappa opioid receptors of rat brain. The mu receptors are most densely localized in patches in the striatum, layers I and III of the cortex, the pyramidal cell layer of the hippocampal formation, specific nuclei of the thalamus, the pars reticulata of the substantia nigra, the interpeduncular nucleus, and the locus coeruleus. In contrast, delta receptors are highly confined, exhibiting selective localization in layers I, II, and VIa of the neocortex, a diffuse pattern in the striatum, and moderate concentration in the pars reticulata of the substantia nigra and in the interpeduncular nucleus. delta receptors are absent in most other brain structures. This distribution is unexpected in that the enkephalins, the putative endogenous ligands of the delta receptor, occur essentially throughout the brain. The kappa receptors of rat brain exhibit a third pattern distinct from that of the mu and delta receptors. kappa receptors occur at low density in patches in the striatum and at particularly high density in the nucleus accumbens, along the pyramidal and molecular layers of the hippocampus, in the granular cell layer of the dentate gyrus, specific midline nuclei of the thalamus, and hindbrain regions. kappa receptors appear to be uniformly distributed across regions in the neocortex with the exception of layer III, which revealed only trace levels of binding. An important conclusion of the present study is that delta receptors occur at high density only in the forebrain and in two midbrain structures, whereas mu and kappa receptors exhibit discrete patterns in most major brain regions

  10. Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

    2016-03-15

    Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Dopamine receptor gene expression by enkephalin neurons in rat forebrain

    International Nuclear Information System (INIS)

    Le Moine, C.; Normand, E.; Guitteny, A.F.; Fouque, B.; Teoule, R.; Bloch, B.

    1990-01-01

    In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of the substantia nigra, ventral tegmental area, and forebrain, especially in caudate putamen, nucleus accumbens, olfactory tubercle, and piriform cortex. Hybridization with D2 and preproenkephalin A probes in adjacent sections, as well as combined hybridization with the two probes in the same sections, demonstrated that all detectable enkephalin neurons in the striatum contained the D2 receptor mRNA. Large neurons in caudate putamen, which were unlabeled with the preproenkephalin A probe and which may have been cholinergic, also expressed the D2 receptor gene. Haloperidol treatment (14 or 21 days) provoked an increase in mRNA content for D2 receptor and preproenkephalin A in the striatum. This suggests that the increase in D2 receptor number observed after haloperidol treatment is due to increased activity of the D2 gene. These results indicate that in the striatum, the enkephalin neurons are direct targets for dopamine liberated from mesostriatal neurons

  12. Dopamine receptor gene expression by enkephalin neurons in rat forebrain

    Energy Technology Data Exchange (ETDEWEB)

    Le Moine, C.; Normand, E.; Guitteny, A.F.; Fouque, B.; Teoule, R.; Bloch, B. (Universite de Bordeaux II (France))

    1990-01-01

    In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of the substantia nigra, ventral tegmental area, and forebrain, especially in caudate putamen, nucleus accumbens, olfactory tubercle, and piriform cortex. Hybridization with D2 and preproenkephalin A probes in adjacent sections, as well as combined hybridization with the two probes in the same sections, demonstrated that all detectable enkephalin neurons in the striatum contained the D2 receptor mRNA. Large neurons in caudate putamen, which were unlabeled with the preproenkephalin A probe and which may have been cholinergic, also expressed the D2 receptor gene. Haloperidol treatment (14 or 21 days) provoked an increase in mRNA content for D2 receptor and preproenkephalin A in the striatum. This suggests that the increase in D2 receptor number observed after haloperidol treatment is due to increased activity of the D2 gene. These results indicate that in the striatum, the enkephalin neurons are direct targets for dopamine liberated from mesostriatal neurons.

  13. Ranitidine reduced levodopa-induced dyskinesia in a rat model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Cui G

    2013-12-01

    Full Text Available Guiyun Cui,1,* Xinxin Yang,1,* Xiaoying Wang,2,* Zunsheng Zhang,1 Xuanye Yue,1 Hongjuan Shi,1 Xia Shen11Department of Neurology, 2Department of Ultrasound, the Affiliated Hospital of Xuzhou Medical College, Jiangsu, People’s Republic of China *These authors contributed equally to this workBackground: Chronic administration of levodopa in Parkinson’s disease leads to debilitating involuntary movements, termed levodopa-induced dyskinesia (LID. The pathogenesis of LID is poorly understood. Previous research has shown that histamine H2 receptors are highly expressed in the input (striatum and output (globus pallidus, substantia nigra regions of the basal ganglia, particularly in the GABAergic striatopallidal and striatonigral pathways. Therefore, a histamine H2 receptor antagonist could be used to reduce LID. In the present work, we investigated whether ranitidine has the potential to diminish LID in rats with dyskinesia and explored the underlying mechanisms involved.Methods: A rat model of PD was induced by 6-hydroxydopamine. Valid PD rats were then treated with levodopa (25 mg/kg, intraperitoneally and benserazide (12.5 mg/kg, intraperitoneally for 21 days to induce a rat model of LID. The acute and chronic effects of administration of ranitidine at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg on abnormal involuntary movements, levodopa-induced rotations, and the forelimb adjusting steps test were investigated in LID rats. The chronic effect of ranitidine (10 mg/kg on the expression of Arc and proenkephalin was also evaluated.Results: Levodopa elicited increased dyskinesia in PD rats. Acute ranitidine treatment had no effect on LID, but chronic ranitidine administration (10 mg/kg, 20 mg/kg reduced LID in rats with dyskinesia. Importantly, levodopa-induced rotations were not affected by chronic treatment with ranitidine. In addition, chronic ranitidine (10 mg/kg, 20 mg/kg significantly improved stepping of the lesioned forepaw. Real

  14. Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat nigrostriatal pathway.

    Directory of Open Access Journals (Sweden)

    Tertia D Purves-Tyson

    Full Text Available Adolescent males have an increased risk of developing schizophrenia, implicating testosterone in the precipitation of dopamine-related psychopathology. Evidence from adult rodent brain indicates that testosterone can modulate nigrostriatal dopamine. However, studies are required to understand the role testosterone plays in maturation of dopamine pathways during adolescence and to elucidate the molecular mechanism(s by which testosterone exerts its effects. We hypothesized that molecular indices of dopamine neurotransmission [synthesis (tyrosine hydroxylase, breakdown (catechol-O-methyl transferase; monoamine oxygenase, transport [vesicular monoamine transporter (VMAT, dopamine transporter (DAT] and receptors (DRD1-D5] would be changed by testosterone or its metabolites, dihydrotestosterone and 17β-estradiol, in the nigrostriatal pathway of adolescent male rats. We found that testosterone and dihydrotestosterone increased DAT and VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at the region of the cell bodies, but not in target regions in the striatum. Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia nigra and/or striatum by androgens. These data suggest that increased testosterone at adolescence may change dopamine responsivity of the nigrostriatal pathway by modulating, at a molecular level, the capacity of neurons to transport and respond to dopamine. Further, dopamine turnover was increased in the dorsal striatum following gonadectomy and this was prevented by testosterone replacement. Gene expression changes in the dopaminergic cell body region may serve to modulate both dendritic dopamine feedback inhibition and reuptake in the dopaminergic somatodendritic field as well as dopamine release and re-uptake dynamics at the presynaptic terminals in the striatum. These testosterone-induced changes of molecular indices of dopamine neurotransmission in males are primarily androgen

  15. Neuronal and glial release of (3H)GABA from the rat olfactory bulb

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, E.H.; Cuello, A.C.

    1981-12-01

    Neuronal versus glial components of the (3H)gamma-aminobutyric acid ((3H)GABA) release studies were performed with two different microdissected layers of the olfactory bulb of the rat. In some experiments substantia nigra was used as a GABAergic axonal system and the trigeminal ganglia as a peripheral glial model. Spontaneous release of (3H)GABA was always lower in neuronal elements as compared with glial cells. A veratridine-evoked release was observed from the ONL but not from the trigeminal ganglia. Tetrodotoxin (TTX) abolished the veratridine-evoked release from the ONL, which also showed a partial inhibition when high magnesium concentrations were used in a Ca2+-free solution. beta-Alanine was strongly exchanged with (3H)GABA from the ONL of animals with the olfactory nerve lesioned and from animals with no lesion; but only a small heteroexchange was found from the external plexiform layer. The beta-alanine heteroexchange was able to deplete the releasable GABA store from the ONL of lesioned animals. In nonlesioned animals and the external plexiform layer, the veratridine-stimulated release of (3H)GABA was not significantly reduced after the beta-alanine heteroexchange. Stimulation of the (3H)GABA release by high concentrations of potassium elicited a higher release rate from axonal terminals than from dendrites or glia. Neurones and glia showed a similar inhibition of (3H)GABA release when a high magnesium concentration was added to a calcium-free solution. When D-600 was used as a calcium-flux blocker no inhibition of the release was observed in glial cells, whereas an almost complete blockage was found in both neuronal preparations (substantia nigra and EPL). These results provide further evidence for differential release mechanisms of GABA from CNS neurones and glial cells.

  16. The hTH-GFP reporter rat model for the study of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Lorraine Iacovitti

    Full Text Available Parkinson disease (PD is the second leading neurodegenerative disease in the US. As there is no known cause or cure for PD, researchers continue to investigate disease mechanisms and potential new therapies in cell culture and in animal models of PD. In PD, one of the most profoundly affected neuronal populations is the tyrosine hydroxylase (TH-expressing dopaminergic (DA neurons of the substantia nigra pars compacta (SNpc. These DA-producing neurons undergo degeneration while neighboring DA-producing cells of the ventral tegmental area (VTA are largely spared. To aid in these studies, The Michael J. Fox Foundation (MJFF partnered with Thomas Jefferson University and Taconic Inc. to generate new transgenic rat lines carrying the human TH gene promoter driving EGFP using a 11 kb construct used previously to create a hTH-GFP mouse reporter line. Of the five rat founder lines that were generated, three exhibited high level specific GFP fluorescence in DA brain structures (ie. SN, VTA, striatum, olfactory bulb, hypothalamus. As with the hTH-GFP mouse, none of the rat lines exhibit reporter expression in adrenergic structures like the adrenal gland. Line 12141, with its high levels of GFP in adult DA brain structures and minimal ectopic GFP expression in non-DA structures, was characterized in detail. We show here that this line allows for anatomical visualization and microdissection of the rat midbrain into SNpc and/or VTA, enabling detailed analysis of midbrain DA neurons and axonal projections after toxin treatment in vivo. Moreover, we further show that embryonic SNpc and/or VTA neurons, enriched by microdissection or FACS, can be used in culture or transplant studies of PD. Thus, the hTH-GFP reporter rat should be a valuable tool for Parkinson's disease research.

  17. Evidence of Neurobiological Changes in the Presymptomatic PINK1 Knockout Rat.

    Science.gov (United States)

    Ferris, Craig F; Morrison, Thomas R; Iriah, Sade; Malmberg, Samantha; Kulkarni, Praveen; Hartner, Jochen C; Trivedi, Malav

    2018-01-01

    Genetic models of Parkinson's disease (PD) coupled with advanced imaging techniques can elucidate neurobiological disease progression, and can help identify early biomarkers before clinical signs emerge. PTEN-induced putative kinase 1 (PINK1) helps protect neurons from mitochondrial dysfunction, and a mutation in the associated gene is a risk factor for recessive familial PD. The PINK1 knockout (KO) rat is a novel model for familial PD that has not been neuroradiologically characterized for alterations in brain structure/function, alongside behavior, prior to 4 months of age. To identify biomarkers of presymptomatic PD in the PINK1 -/- rat at 3 months using magnetic resonance imaging techniques. At postnatal weeks 12-13; one month earlier than previously reported signs of motor and cognitive dysfunction, this study combined imaging modalities, including assessment of quantitative anisotropy across 171 individual brain areas using an annotated MRI rat brain atlas to identify sites of gray matter alteration between wild-type and PINK1 -/- rats. The olfactory system, hypothalamus, thalamus, nucleus accumbens, and cerebellum showed differences in anisotropy between experimental groups. Molecular analyses revealed reduced levels of glutathione, ATP, and elevated oxidative stress in the substantia nigra, striatum and deep cerebellar nuclei. Mitochondrial genes encoding proteins in Complex IV, along with mRNA levels associated with mitochondrial function and genes involved in glutathione synthesis were reduced. Differences in brain structure did not align with any cognitive or motor impairment. These data reveal early markers, and highlight novel brain regions involved in the pathology of PD in the PINK1 -/- rat before behavioral dysfunction occurs.

  18. Finasteride inhibited brain dopaminergic system and open-field behaviors in adolescent male rats.

    Science.gov (United States)

    Li, Li; Kang, Yun-Xiao; Ji, Xiao-Ming; Li, Ying-Kun; Li, Shuang-Cheng; Zhang, Xiang-Jian; Cui, Hui-Xian; Shi, Ge-Ming

    2018-02-01

    Finasteride inhibits the conversion of testosterone to dihydrotestosterone. Because androgen regulates dopaminergic system in the brain, it could be hypothesized that finasteride may inhibit dopaminergic system. The present study therefore investigates the effects of finasteride in adolescent and early developmental rats on dopaminergic system, including contents of dopamine and its metabolites (dihydroxy phenyl acetic acid and homovanillic acid) and tyrosine hydroxylase expressions both at gene and protein levels. Meanwhile, open-field behaviors of the rats are examined because of the regulatory effect of dopaminergic system on the behaviors. Open-field behaviors were evaluated by exploratory and motor behaviors. Dopamine and its metabolites were assayed by liquid chromatography-mass spectrometry. Tyrosine hydroxylase mRNA and protein expressions were determined by real-time qRT-PCR and western blot, respectively. It was found that in adolescent male rats, administration of finasteride at doses of 25 and 50 mg/kg for 14 days dose dependently inhibited open-field behaviors, reduced contents of dopamine and its metabolites in frontal cortex, hippocampus, caudate putamen, nucleus accumbens, and down-regulated tyrosine hydroxylase mRNA and protein expressions in substantia nigra and ventral tegmental area. However, there was no significant change of these parameters in early developmental rats after finasteride treatment. These results suggest that finasteride inhibits dopaminergic system and open-field behaviors in adolescent male rats by inhibiting the conversion of testosterone to dihydrotestosterone, and imply finasteride as a potential therapeutic option for neuropsychiatric disorders associated with hyperactivities of dopaminergic system and androgen. © 2017 John Wiley & Sons Ltd.

  19. Panicolytic-like effects caused by substantia nigra pars reticulata pretreatment with low doses of endomorphin-1 and high doses of CTOP or the NOP receptors antagonist JTC-801 in male Rattus norvegicus.

    Science.gov (United States)

    da Silva, Juliana Almeida; Biagioni, Audrey Franceschi; Almada, Rafael Carvalho; de Freitas, Renato Leonardo; Coimbra, Norberto Cysne

    2017-10-01

    Gamma-aminobutyric acid (GABA)ergic neurons of the substantia nigra pars reticulata (SNpr) are connected to the deep layers of the superior colliculus (dlSC). The dlSC, in turn, connect with the SNpr through opioid projections. Nociceptin/orphanin FQ peptide (N/OFQ) is a natural ligand of a Gi protein-coupled nociceptin receptor (ORL1; NOP) that is also found in the SNpr. Our hypothesis is that tectonigral opioid pathways and intranigral orphanin-mediated mechanisms modulate GABAergic nigrotectal connections. Therefore, the aim of this work was to study the role of opioid and NOP receptors in the SNpr during the modulation of defence reactions organised by the dlSC. The SNpr was pretreated with either opioid or NOP receptor agonists and antagonists, followed by dlSC treatment with bicuculline. Blockade of GABA A receptors in the dlSC elicited fear-related defensive behaviour. Pretreatment of the SNpr with naloxone benzoylhydrazone (NalBzoH), a μ-, δ-, and κ 1 -opioid receptor antagonist as well as a NOP receptor antagonist, decreased the aversive effect of bicuculline treatment on the dlSC. Either μ-opioid receptor activation or blockade by SNpr microinjection of endomorphin-1 (EM-1) and CTOP promoted pro-aversive and anti-aversive actions, respectively, that modulated the defensive responses elicited by bicuculline injection into the dlSC. Pretreatment of the SNpr with the selective NOP receptor antagonist JTC801 decreased the aversive effect of bicuculline, and microinjections of the selective NOP receptor agonist NNC 63-0532 promoted the opposite effect. These results demonstrate that opioid pathways and orphanin-mediated mechanisms have a critical role in modulating the activity of nigrotectal GABAergic pathways during the organisation of defensive behaviours.

  20. Ontogeny of phorbol ester receptors in rat brain studied by in vitro autoradiography

    International Nuclear Information System (INIS)

    Miyoshi, R.; Kito, S.

    1990-01-01

    The ontogeny of phorbol ester receptors, which have been considered to correspond to protein kinase C, in the rat brain was studied through in vitro autoradiography with 3 H-phorbol 12,13-dibutyrate ( 3 H-PDBu). The distribution of 3 H-PDBu binding sites in the adult rat brain was similar to the previous reports by other researchers. The developmental pattern of 3 H-PDBu binding sites varried with brain region. 3 H-PDBu binding sites in the amygdala, thalamus, stratum pyramidale of CA 1 of the hippocampus, dentate gyrus, superior colliculus, substantia nigra, interpeduncular nucleus and cerebellar molecular layer were postnatally increased to adult levels and after that they remained constant. On the other hand, in the stratum oriens and stratum radiatum of CA 1 of the hippocampus, and in the lateral and medial geniculate bodies, 3 H-PDBu binding sites reached peaks at 21 or 28 days of postnatal age and after that they declined to adult levels. The cerebellar granular layer showed a low level of 3 H-PDBu binding sites throughout all the ontogenetic stages. A distinct ontogenetic pattern of phorbol ester receptors in various regions of the brain may reflect a role of protein kinase C in the neural development of each discrete area. (Authors)

  1. A wireless multi-channel recording system for freely behaving mice and rats.

    Science.gov (United States)

    Fan, David; Rich, Dylan; Holtzman, Tahl; Ruther, Patrick; Dalley, Jeffrey W; Lopez, Alberto; Rossi, Mark A; Barter, Joseph W; Salas-Meza, Daniel; Herwik, Stanislav; Holzhammer, Tobias; Morizio, James; Yin, Henry H

    2011-01-01

    To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.

  2. A wireless multi-channel recording system for freely behaving mice and rats.

    Directory of Open Access Journals (Sweden)

    David Fan

    Full Text Available To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.

  3. Chronic lead intoxication affects glial and neural systems and induces hypoactivity in adult rat.

    Science.gov (United States)

    Sansar, Wafa; Ahboucha, Samir; Gamrani, Halima

    2011-10-01

    Lead is an environmental toxin and its effects are principally manifested in the brain. Glial and neuronal changes have been described during development following chronic or acute lead intoxication, however, little is known about the effects of chronic lead intoxication in adults. In this study we evaluated immunohistochemically the glial and dopaminergic systems in adult male Wistar rats. 0.5% (v/v) lead acetate in drinking water was administrated chronically over a 3-month period. Hypertrophic immunoreactive astrocytes were observed in the frontal cortex and other brain structures of the treated animals. Analysis of the astroglial features showed increased number of astrocyte cell bodies and processes in treated rats, an increase confirmed by Western blot. Particular distribution of glial fibrillary acidic protein immunoreactivity was observed within the blood vessel walls in which dense immunoreactive glial processes emanate from astrocytes. Glial changes in the frontal cortex were concomitant with reduced tyrosine hydroxylase immunoreactive neuronal processes, which seem to occur as a consequence of significantly reduced dopaminergic neurons within the nucleus of origin in the substantia nigra. These glial and neuronal changes following lead intoxication may affect animal behavior as evidenced by reduced locomotor activity in an open field test. These findings demonstrate that chronic lead exposure induces astroglial changes, which may compromise neuronal function and consequently animal behavior. Copyright © 2010 Elsevier GmbH. All rights reserved.

  4. Regional blockade by neuroleptic drugs of in vivo /sup 3/H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies

    Energy Technology Data Exchange (ETDEWEB)

    Koehler, C; Haglund, L; Oegren, S O; Aengeby, T [Astra Lackemedel AB, Soedertaelje (Sweden). Dept. of Pharmacology

    1981-01-01

    The regional prevention by neuroleptic drugs of specific in vivo /sup 3/H-spiperone binding was studied in the rat brain. L-sulpiride, thioridazine and clozapine were found to reduce the /sup 3/H-spiperone bindings selectively in the olfactory tubercle, septum, substantia nigra and frontal cortex but not the striatum at dose levels which preferentially block apomorphine (APO) induced hyperactivity. The maximal prevention of specific /sup 3/H-spiperone binding by l-sulpiride and clozapine reached 60-80% in the former structures while the displacement of striatal /sup 3/H-spiperone binding did not exceed 40%. In contrast to l-sulpiride, thioridazine and clozapine both chlorpromazine and haloperidol reduced the /sup 3/H-spiperone binding to the same extent in all regions studied. Chlorpromazine and haloperidol were potent in prevention of striatal /sup 3/H-spiperone binding in vivo which reached 60-80% in this structure.

  5. Regional blockade by neuroleptic drugs of in vivo 3H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies

    International Nuclear Information System (INIS)

    Koehler, C.; Haglund, L.; Oegren, S.-O.; Aengeby, T.

    1981-01-01

    The regional prevention by neuroleptic drugs of specific in vivo 3 H-spiperone binding was studied in the rat brain. L-sulpiride, thioridazine and clozapine were found to reduce the 3 H-spiperone bindings selectively in the olfactory tubercle, septum, substantia nigra and frontal cortex but not the striatum at dose levels which preferentially block apomorphine (APO) induced hyperactivity. The maximal prevention of specific 3 H-spiperone binding by l-sulpiride and clozapine reached 60-80% in the former structures while the displacement of striatal 3 H-spiperone binding did not exceed 40%. In contrast to l-sulpiride, thioridazine and clozapine both chlorpromazine and haloperidol reduced the 3 H-spiperone binding to the same extent in all regions studied. Chlorpromazine and haloperidol were potent in prevention of striatal 3 H-spiperone binding in vivo which reached 60-80% in this structure. (Author)

  6. RatMap--rat genome tools and data.

    Science.gov (United States)

    Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M; Ståhl, Fredrik

    2005-01-01

    The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB-Genetics at Goteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.

  7. Region-specific differences in bioenergetic proteins and protein response to acute high fat diet in brains of low and high capacity runner rats.

    Science.gov (United States)

    Gan, Li; Ma, Delin; Li, Min; Yang, Fu-Chen; Rogers, Robert S; Wheatley, Joshua L; Koch, Lauren G; Britton, Steven L; Thyfault, John P; Geiger, Paige C; Stanford, John A

    2018-05-01

    Aerobic capacity is a strong predictor of mortality. Low capacity runner (LCR) rats exhibit reduced mitochondrial function in peripheral organs. A high fat diet (HFD) can worsen metabolic phenotype in LCR rats. Little is known about metabolic changes in the brains of these rats, however. This study examined protein markers of mitochondrial function and metabolism as a function of aerobic running capacity and an acute HFD in four brain regions: the striatum, hippocampus, hypothalamus, and substantia nigra. After 3 days HFD or chow diets, we measured peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1-α), nuclear respiratory factors 1 (Nrf-1), mitochondrial transcription factor A (TFAM), and phosphorylated (activated) AMP-activated protein kinase (p-AMPK) protein levels in the four brain regions. LCR rats exhibited lower levels of mitochondrial proteins (PGC1-α, Nrf-1, TFAM), and greater p-AMPK, in striatum, but not in the other brain regions. Mitochondrial protein levels were greater in HFD LCR striatum, while p-AMPK was lower in this group. Markers of lower mitochondrial biogenesis and increased metabolic demand were limited to the LCR striatum, which nevertheless maintained the capacity to respond to an acute HFD challenge. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    M.M. Ferro

    2007-01-01

    Full Text Available There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg and xylazine (3 mg/kg (K/X on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP or 6-hydroxydopamine (6-OHDA rat models of Parkinson's disease. The bilateral infusion of MPTP (100 µg/side or 6-OHDA (10 µg/side into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67% or severe (~91% loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.

  9. Induction of Fos protein immunoreactivity by spinal cord contusion

    Directory of Open Access Journals (Sweden)

    E.A. Del-Bel

    2000-05-01

    Full Text Available The objective of the present study was to identify neurons in the central nervous system that respond to spinal contusion injury in the rat by monitoring the expression of the nuclear protein encoded by the c-fos gene, an activity-dependent gene, in spinal cord and brainstem regions. Rats were anesthetized with urethane and the injury was produced by dropping a 5-g weight from 20.0 cm onto the exposed dura at the T10-L1 vertebral level (contusion group. The spinal cord was exposed but not lesioned in anesthetized control animals (laminectomy group; intact animals were also subjected to anesthesia (intact control. Behavioral alterations were analyzed by Tarlov/Bohlman scores, 2 h after the procedures and the animals were then perfused for immunocytochemistry. The patterns of Fos-like immunoreactivity (FLI which were site-specific, reproducible and correlated with spinal laminae that respond predominantly to noxious stimulation or injury: laminae I-II (outer substantia gelatinosa and X and the nucleus of the intermediolateral cell column. At the brain stem level FLI was detected in the reticular formation, area postrema and solitary tract nucleus of lesioned animals. No Fos staining was detected by immunocytochemistry in the intact control group. However, detection of FLI in the group submitted to anesthesia and surgical procedures, although less intense than in the lesion group, indicated that microtraumas may occur which are not detected by the Tarlov/Bohlman scores. There is both a local and remote effect of a distal contusion on the spinal cord of rats, implicating sensory neurons and centers related to autonomic control in the reaction to this kind of injury.

  10. Correlative single photon emission computed tomography imaging of [123I]altropane binding in the rat model of Parkinson's

    International Nuclear Information System (INIS)

    Gleave, Jacqueline A.; Farncombe, Troy H.; Saab, Chantal; Doering, Laurie C.

    2011-01-01

    Introduction: This study used the dopamine transporter (DAT) probe, [ 123 I]-2β-carbomethoxy-3β-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane ([ 123 I]altropane), to assess the DAT levels in the 6-hydroxydopamine rat model of Parkinson's disease. We sought to assess if the right to left [ 123 I]altropane striatal ratios correlated with dopamine content in the striatum and substantia nigra and with behavioural outcomes. Methods: [ 123 I]altropane images taken pre- and postlesion were acquired before and after the transplantation of neural stem/progenitor cells. The images obtained using [ 123 I]altropane and single photon emission computed tomography (SPECT) were compared with specific behavioural tests and the dopamine content assessed by high-performance liquid chromatography. Results: [ 123 I]altropane binding correlated with the content of dopamine in the striatum; however, [ 123 I]altropane binding did not correlate with the dopamine content in the substantia nigra. There was a significant correlation of altropane ratios with the cylinder test and the postural instability test, but not with amphetamine rotations. The low coefficient of determination (r 2 ) for these correlations indicated that [ 123 I]altropane SPECT was not a good predictor of behavioural outcomes. Conclusion: Our data reveal that [ 123 I]altropane predicts the integrity of the striatal dopamine nerve terminals, but does not predict the integrity of the nigrostriatal system. [ 123 I]altropane could be a useful marker to measure dopamine content in cell replacement therapies; however, it would not be able to evaluate outcomes for neuroprotective strategies.

  11. Neuroprotective effects of lentivirus-mediated cystathionine-beta-synthase overexpression against 6-OHDA-induced parkinson's disease rats.

    Science.gov (United States)

    Yin, Wei-Lan; Yin, Wei-Guo; Huang, Bai-Sheng; Wu, Li-Xiang

    2017-09-14

    Parkinson's disease (PD) is age-related neurodegenerative disorder by a progressive loss of dopaminergic(DA) neurons in the substantia nigra (SN) and striatum, which is at least partly associated with α-synuclein protein accumulation in these neurons. Hydrogen sulfide (H 2 S) plays an important role in the nervous system. Studies have shown that H 2 S has a protective effect on PD. However, as a kind of gas molecules, H 2 S is lively, volatile, and not conducive to scientific research and clinical application. Cystathionine-beta-synthase(CBS) is the main enzymes of synthesis of H 2 S in the brain. In order to examine the neuroprotective effects of CBS on PD, we detected the effects of CBS overexpression on 6-Hydroxydopamine (6-OHDA)-lesioned PD rats using lentivirus-mediated gene transfection techniques. In the injured SN of 6-OHDA-induced PD rats, the CBS expression and the endogenous H 2 S level markedly decreased, while administration of lentivirus-mediated CBS overexpression increased the CBS expression and the endogenous H 2 S production.CBS overexpression dramatically reversed apomorphine-induced rotation of the 6-OHDA model rats, decreased the number of TUNEL-positive neurons and the loss of the nigral DA neurons,specifically inhibited 6-OHDA-induced oxidase stress injury, and down-regulated the expression of α-synuclein(α-SYN) in the injured SN. NaHS (an H 2 S donor) had similar effects to CBS overexpression, while Amino-oxyacetate(AOAA, a CBS inhibitor) had opposite effects on PD rats. In summary, we demonstrated that CBS overexpression was able to provide neuroprotective on PD rats and improving the expression of CBS may be a potential therapeutic method for PD. Copyright © 2017. Published by Elsevier B.V.

  12. Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum Neurotoxin-A Injection.

    Science.gov (United States)

    Mann, T; Zilles, K; Dikow, H; Hellfritsch, A; Cremer, M; Piel, M; Rösch, F; Hawlitschka, A; Schmitt, O; Wree, A

    2018-03-15

    Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D 1 , D 2 /D 3 , α 1 , α 2 , and 5HT 2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D 1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D 2 /D 3 receptor density, and 50% reduction in 5HT 2A receptor density. α 1 receptor density remained unaltered in hemi-PD and α 2 receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D 2 /D 3 receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D 2 /D 3 receptor density. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Effects of glutamate and α2-noradrenergic receptor antagonists on the development of neurotoxicity produced by chronic rotenone in rats

    International Nuclear Information System (INIS)

    Alam, Mesbah; Danysz, Wojciech; Schmidt, Werner Juergen; Dekundy, Andrzej

    2009-01-01

    Systemic inhibition of complex I by rotenone in rats represents a model of Parkinson's disease (PD). The aim of this study was to elucidate whether neramexane (NMDA, nicotinic α9/α10 and 5-HT 3 receptor antagonist), idazoxan (α 2 -adrenoceptor antagonist) or 2-methyl-6-(phenyl-ethyl)-pyrimidine (MPEP, metabotropic glutamate receptor 5 antagonist) prevents rotenone-induced parkinsonian-like behaviours and neurochemical changes in rats. Rotenone (2.5 mg/kg i.p. daily) was administered over 60 days together with saline, neramexane (5 mg/kg i.p., b.i.d.), idazoxan (2.5 mg/kg i.p., b.i.d.) or MPEP (2.5 mg/kg i.p., b.i.d.). The same doses of neramexane, idazoxan and MPEP were administered to rats treated with vehicle instead of rotenone. Treatment-related effects on parkinsonian-like behaviours, such as hypokinesia/rigidity and locomotor activity, were evaluated. Moreover, concentrations of dopamine, serotonin and their metabolites were measured in rats from each experimental group. Over the 60-day treatment period, the rotenone + saline treated animals developed hypokinesia, expressed as an increase in the bar and grid descent latencies in the catalepsy test, and a decrease in locomotor activity. Neramexane and idazoxan partially prevented the development of catalepsy in rotenone-treated rats. Co-administration of MPEP with rotenone resulted only in a decrease in descent latency in the grid test on day 60. Chronic rotenone treatment reduced concentrations of dopamine and serotonin in the anterior striatum, which was blocked by co-treatment with neramexane or idazoxan but not with MPEP. Only neramexane treatment blocked the rotenone-induced decrease in dopamine levels in the substantia nigra pars compacta. In conclusion, neramexane and idazoxan counteracted to some extent the development of parkinsonian symptoms and neurochemical alterations in the rotenone model of Parkinson's disease.

  14. Effects of discontinuing a high-fat diet on mitochondrial proteins and 6-hydroxydopamine-induced dopamine depletion in rats.

    Science.gov (United States)

    Ma, Delin; Shuler, Jeffrey M; Raider, Kayla D; Rogers, Robert S; Wheatley, Joshua L; Geiger, Paige C; Stanford, John A

    2015-07-10

    Diet-induced obesity can increase the risk for developing age-related neurodegenerative diseases including Parkinson's disease (PD). Increasing evidence suggests that mitochondrial and proteasomal mechanisms are involved in both insulin resistance and PD. The goal of this study was to determine whether diet intervention could influence mitochondrial or proteasomal protein expression and vulnerability to 6-Hydroxydopamine (6-OHDA)-induced nigrostriatal dopamine (DA) depletion in rats' nigrostriatal system. After a 3 month high-fat diet regimen, we switched one group of rats to a low-fat diet for 3 months (HF-LF group), while the other half continued with the high-fat diet (HF group). A chow group was included as a control. Three weeks after unilateral 6-OHDA lesions, HF rats had higher fasting insulin levels and higher Homeostasis model assessment of insulin resistance (HOMA-IR), indicating insulin resistance. HOMA-IR was significantly lower in HF-LF rats than HF rats, indicating that insulin resistance was reversed by switching to a low-fat diet. Compared to the Chow group, the HF group exhibited significantly greater DA depletion in the substantia nigra but not in the striatum. DA depletion did not differ between the HF-LF and HF group. Proteins related to mitochondrial function (such as AMPK, PGC-1α), and to proteasomal function (such as TCF11/Nrf1) were influenced by diet intervention, or by 6-OHDA lesion. Our findings suggest that switching to a low-fat diet reverses the effects of a high-fat diet on systemic insulin resistance, and mitochondrial and proteasomal function in the striatum. Conversely, they suggest that the effects of the high-fat diet on nigrostriatal vulnerability to 6-OHDA-induced DA depletion persist. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease.

    Directory of Open Access Journals (Sweden)

    Jackalina M Van Kampen

    Full Text Available The development of effective neuroprotective therapies for Parkinson's disease (PD has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the

  16. Rat Genome Database (RGD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Rat Genome Database (RGD) is a collaborative effort between leading research institutions involved in rat genetic and genomic research to collect, consolidate,...

  17. Daily chronomics of proteomic profile in aging and rotenone-induced Parkinson's disease model in male Wistar rat and its modulation by melatonin.

    Science.gov (United States)

    Jagota, Anita; Mattam, Ushodaya

    2017-08-01

    Aging is associated with changes in several basic parameters of circadian timing system (CTS) in mammals leading to circadian dysfunction. We had reported earlier that upon aging and in rotenone induced Parkinson's disease (RIPD) rat model there were significant alterations in the core clock genes expression levels and daily pulses. To identify biomarkers of aging and PD chronomics of proteomic day-night profiles in suprachiasmatic nucleus (SCN), pineal and substantia nigra (SN) in 3 month (m), 12, 24 m and RIPD rat model were studied at two time points i.e. Zeitgeber Time (ZT)-6 (mid-day) and ZT-18 (mid-night). Proteome analysis was done by using two dimensional (2-D) electrophoresis and the spots showing robust day-night variations were identified by using MALDI TOF/TOF analysis. In 3 m rats the number of proteins showing day-night variations were relatively more than 12, 24 m and RIPD rat model in SCN and SN. But in pineal there was increase in number of protein spots showing day-night variations in 24 m. Mass spectroscopy of the protein spots showing robust day night variation in aging and RIPD rats were identified. As melatonin, a multitasking molecule, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging, the effects of melatonin administration on differential alterations in chronomics of 2-D protein profiles in aging and RIPD male Wistar rats were studied. We report here that the melatonin could be playing an important role in modulating the chronomics of 2-D protein profiles. Additionally, various proteins were identified for the first time in this study showing significant day night variation in SCN, pineal and SN may prove useful towards targeting novel treatments for circadian dysfunction, good health and longevity.

  18. Autoradiographic localization of 3H-paroxetine-labeled serotonin uptake sites in rat brain

    International Nuclear Information System (INIS)

    De Souza, E.B.; Kuyatt, B.L.

    1987-01-01

    Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin

  19. Metabolic-dopaminergic mapping of the 6-hydroxydopamine rat model for Parkinson's disease

    International Nuclear Information System (INIS)

    Casteels, Cindy; Lauwers, Erwin; Baekelandt, Veerle; Bormans, Guy; Laere, Koen van

    2008-01-01

    The unilateral 6-hydroxydopamine (6-OHDA) lesion rat model is a well-known acute model for Parkinson's disease (PD). Its validity has been supported by invasive histology, behavioral studies and electrophysiology. Here, we have characterized this model in vivo by multitracer imaging [glucose metabolism and dopamine transporter (DAT)] in relation to behavioral and histological parameters. Eighteen female adult Wistar rats (eight 6-OHDA-lesioned, ten controls) were investigated using multitracer [ 18 F]-fluoro-2-deoxy-D-glucose (FDG) and [ 18 F]-FECT 2'-[ 18 F]-fluoroethyl-(1R-2-exo-3-exe)-8-methyl-3-(4-chlorophenyl)- 8-azabicyclo (3.2.1)-octane-2-carboxylate small animal positron emission tomography (PET). Relative glucose metabolism and parametric DAT binding images were anatomically standardized to Paxinos space and analyzed on a voxel-basis using SPM2, supplemented by a template-based predefined volumes-of-interest approach. Behavior was characterized by the limb-use asymmetry test; dopaminergic innervation was validated by in vitro tyrosine hydroxylase staining. In the 6-OHDA model, significant glucose hypometabolism is present in the ipsilateral sensory-motor cortex (-6.3%; p = 4 x 10 -6 ). DAT binding was severely decreased in the ipsilateral caudate-putamen, nucleus accumbens and substantia nigra (all p -9 ), as confirmed by the behavioral and histological outcomes. Correlation analysis revealed a positive relationship between the degree of DAT impairment and the change in glucose metabolism in the ipsilateral hippocampus (p = 3 x 10 -5 ), while cerebellar glucose metabolism was inversely correlated to the level of DAT impairment (p -4 ). In vivo cerebral mapping of 6-OHDA-lesioned rats using [ 18 F ]-FDG and [ 18 F ]-FECT small animal PET shows molecular-functional correspondence to the cortico-subcortical network impairments observed in PD patients. This provides a further molecular validation supporting the validity of the 6-OHDA lesion model to mimic

  20. Afferent projections to the deep mesencephalic nucleus in the rat

    International Nuclear Information System (INIS)

    Veazey, R.B.; Severin, C.M.

    1982-01-01

    Afferent projections to the deep mesencephalic nucleus (DMN) of the rat were demonstrated with axonal transport techniques. Potential sources for projections to the DMN were first identified by injecting the nucleus with HRP and examining the cervical spinal cord, brain stem, and cortex for retrogradely labeled neurons. Areas consistently labeled were then injected with a tritiated radioisotope, the tissue processed for autoradiography, and the DMN examined for anterograde labeling. Afferent projections to the medial and/or lateral parts of the DMN were found to originate from a number of spinal, bulbar, and cortical centers. Rostral brain centers projecting to both medial and lateral parts of the DMN include the ipsilateral motor and somatosensory cortex, the entopeduncular nucleus, and zona incerta. at the level of the midbrain, the ipsilateral substantia nigra and contralateral DMN likewise project to the DMN. Furthermore, the ipsilateral superior colliculus projects to the DMN, involving mainly the lateral part of the nucleus. Afferents from caudal centers include bilateral projections from the sensory nucleus of the trigeminal complex and the nucleus medulla oblongata centralis, as well as from the contralateral dentate nucleus. The projections from the trigeminal complex and nucleus medullae oblongatae centralis terminate in the intermediate and medial parts of the DMN, whereas projections from the contralateral dentate nucleus terminate mainly in its lateral part. In general, the afferent connections of the DMN arise from diverse areas of the brain. Although most of these projections distribute throughout the entire extent of the DMN, some of them project mainly to either medial or lateral parts of the nucleus, thus suggesting that the organization of the DMN is comparable, at least in part, to that of the reticular formation of the pons and medulla, a region in which hodological differences between medial and lateral subdivisions are known to exist

  1. Neuroprotective effect of curcumin-I in copper-induced dopaminergic neurotoxicity in rats: A possible link with Parkinson's disease.

    Science.gov (United States)

    Abbaoui, Abdellatif; Chatoui, Hicham; El Hiba, Omar; Gamrani, Halima

    2017-11-01

    Numerous findings indicate an involvement of heavy metals in the neuropathology of several neurodegenerative disorders, especially Parkinson's disease (PD). Previous studies have demonstrated that Copper (Cu) exhibits a potent neurotoxic effect on dopaminergic neurons and triggers profound neurobehavioral alterations. Curcumin is a major component of Curcuma longa rhizomes and a powerful medicinal plant that exerts many pharmacological effects. However, the neuroprotective action of curcumin on Cu-induced dopaminergic neurotoxicity is yet to be investigated. The aim of the present study was to evaluate the impact of acute Cu-intoxication (10mg/kg B.W. i.p) for 3days on the dopaminergic system and locomotor performance as well as the possible therapeutic efficacy of curcumin I (30mg/kg B.W.). Intoxicated rats showed a significant loss of Tyrosine Hydroxylase (TH) expression within substantia nigra pars compacta (SNc), ventral tegmental area (VTA) and the striatal outputs. This was correlated with a clear decrease in locomotor performance. Critically, curcumin-I co-treatment reversed these changes and showed a noticeable protective effect; both TH expression and locomotor performance was reinstated in intoxicated rats. These results demonstrate altered dopaminergic innervations following Cu intoxication and a new therapeutic potential of curcumin against Cu-induced dopaminergic neurotransmission failure. Curcumin may therefore prevent heavy metal related Parkinsonism. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Differences between high-affinity forskolin binding sites in dopamine-riche and other regions of rat brain

    International Nuclear Information System (INIS)

    Poat, J.A.; Cripps, H.E.; Iversen, L.L.

    1988-01-01

    Forskolin labelled with [ 3 H] bound to high- and low-affinity sites in the rat brain. The high-affinity site was discretely located, with highest densities in the striatum, nucleus accumbens, olfactory tubercule, substantia nigra, hippocampus, and the molecular layers of the cerebellum. This site did not correlate well with the distribution of adenylate cyclase. The high-affinity striatal binding site may be associated with a stimulatory guanine nucleotide-binding protein. Thus, the number of sites was increased by the addition of Mg 2+ and guanylyl imidodiphosphate. Cholera toxin stereotaxically injected into rat striatum increased the number of binding sites, and no further increase was noted following the subsequent addition of guanyl nucleotide. High-affinity forskolin binding sites in non-dopamine-rich brain areas (hippocampus and cerebullum) were modulated in a qualitatively different manner by guanyl nucleotides. In these areas the number of binding sites was significantly reduced by the addition of guanyl nucleotide. These results suggest that forskolin may have a potential role in identifying different functional/structural guanine nucleotide-binding proteins

  3. Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model

    Science.gov (United States)

    Zheng, Deyu; Jiang, Xiaohua; Zhao, Junpeng; Duan, Deyi; Zhao, Huanying; Xu, Qunyuan

    2013-01-01

    The aim of the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson’s disease (PD). Here, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human glutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex vivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior was improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65 gene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control groups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This study suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD model rats, independent of the protection the DA neurons from death. PMID:23738148

  4. Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

    Energy Technology Data Exchange (ETDEWEB)

    See, R E; Ellison, G; Toga, A W [California Univ., Los Angeles, CA (USA). School of Medicine

    1990-01-01

    Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2(({sup 3}H)spiperone and ({sup 3}H)raclopride), dopamine D1(({sup 3}H)SCH23390), GABA{sub A}(({sup 3}H)muscimol), benzodiazepine (({sup 3}H)RO15-1788), and muscarinic ACh receptors (({sup 3}H)QNB). ({sup 3}H)spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal ({sup 3}H)raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in ({sup 3}H)SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in ({sup 3}H)muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of ({sup 3}H)QNB and ({sup 3}H)RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors).

  5. Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Anna Ljungdahl

    Full Text Available L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors

  6. Glycine: an alternative transmitter candidate of the pallidosubthalamic projection neurons in the rat

    International Nuclear Information System (INIS)

    Takada, M.; Hattori, T.

    1987-01-01

    Autoradiographic retrograde tracing techniques with radioactive transmitters were used to analyse the identity of a putative transmitter in the rat pallidosubthalamic (GP-STN) pathway. One to 2 hours after the stereotaxic injection of 3 H-glycine restricted to the STN, a large number of neuronal somata were radiolabeled in the GP. No comparable labeling was observed following the injection of 3 H-gamma-aminobutyric acid ( 3 H-GABA) into the same nucleus even with survival times as long as 6 hours. Specifically, no significant somatic labeling was detected either in the GP or in the caudoputamen (CPU). Only when 3 H-GABA was injected into the substantia nigra did CPU and GP neurons become labeled. On the contrary, STN neuronal somata were invariably labeled 6 hours after the intrapallidal injection of 3 H-GABA, whereas no perikaryal labeling was observed in the STN after 3 H-glycine injection into the GP. The perikaryal labeling was prevented in all cases by intraventricular administration of colchicine 1 day before the isotope injections. The observations suggest that 3 H-glycine was preferentially transported retrogradely through the GP-STN pathway, and 3 H-GABA through the STN-GP projection. In view of the recent controversy on the role of GABA as a putative transmitter of the GP-STN projection, we now propose glycine as an alternative transmitter candidate of these critically situated neurons in the basal ganglia

  7. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors

    International Nuclear Information System (INIS)

    Pazos, A.; Palacios, M.

    1985-01-01

    The distribution of serotonin-1 (5-HT 1 ) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with [ 3 H]serotonin (5-[ 3 H]HT), 8-hydroxy-2-[N-dipropylamino- 3 H]tetralin (8-OH-[ 3 H]DPAT), [ 3 H]LSD and [ 3 H]mesulergine, and the densities quantified by microdensitometry with the aid of a computer-assisted image-analysis system. Competition experiments for 5-[ 3 H]HT binding by several serotonin-1 agonists led to the identification of brain areas enriched in each one of the three subtypes of 5-HT 1 recognition sites already described. The existence of these 'selective' areas allowed a detailed pharmacological characterization of these sites to be made in a more precise manner than has been attained in membrane-binding studies. Very high concentrations of 5-HT 1 receptors were localized in the choroid plexus, lateroseptal nucleus, globus pallidus and ventral pallidum, dentate gyrus, dorsal subiculum, olivary pretectal nucleus, substantia nigra, reticular and external layer of the entorhinal cortex. The distribution of 5-HT 1 receptors reported here is discussed in correlation with the distribution of serotoninergic neurons and fibers, the related anatomical pathways and the effects which appear to be mediated by these sites. (Auth.)

  8. Utility of a tripolar stimulating electrode for eliciting dopamine release in the rat striatum.

    Science.gov (United States)

    Bergstrom, B P; Garris, P A

    1999-03-01

    The present study evaluated tripolar stimulating electrodes for eliciting dopamine release in the rat brain in vivo. Stimulating electrodes were placed either in the medial forebrain bundle or in the ventral mesencephalon associated with the ventral tegmental area and substantia nigra. The concentration of extracellular dopamine was monitored in dopamine terminal fields at 100-ms intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To characterize the stimulated area, recordings were collected in several striatal regions including the caudate putamen and the core and shell of the nucleus accumbens. The tripolar electrode was equally effective in stimulating dopamine release in medial and lateral regions of the striatum. In contrast, responses evoked by a bipolar electrode were typically greater in one mediolateral edge versus the other. The added size of the tripolar electrode did not appear to cause complications as signals were stable over the course of the experiment (3 h). Subsets of mesostriatal dopamine neurons could also be selectively activated using the tripolar electrode in excellent agreement with previously described topography. Taken together, these results suggested that the tripolar stimulating electrode is well suited for studying the regulation of midbrain dopamine neurons in vivo.

  9. Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain

    International Nuclear Information System (INIS)

    Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.

    1986-01-01

    The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40% increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism

  10. Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain

    International Nuclear Information System (INIS)

    Worley, P.F.; Baraban, J.M.

    1987-01-01

    The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using [ 3 H]batrachotoxinin-A 20-alpha-benzoate (BTX-B). Binding of [ 3 H]BTX-B to brain sections is dependent on potentiating allosteric interactions with scorpion venom and is displaced by BTX-B (Kd approximately 200 nM), aconitine, veratridine, and phenytoin with the same rank order of potencies as described in brain synaptosomes. The maximum number of [ 3 H]BTX-B binding sites in forebrain sections also agrees with biochemical determinations. Autoradiographic localizations indicate that [ 3 H]BTX-B binding sites are not restricted to cell bodies and axons but are present in synaptic zones throughout the brain. For example, a particularly dense concentration of these sites in the substantia nigra is associated with afferent terminals of the striatonigral projection. By contrast, myelinated structures possess much lower densities of binding sites. In addition, we present electrophysiological evidence that synaptic transmission, as opposed to axonal conduction, is preferentially sensitive to the action of aconitine and veratridine. Finally, the synaptic block produced by these sodium channel activators is inhibited by phenytoin and carbamazepine at therapeutic anticonvulsant concentrations

  11. Topographic Organization of Cholinergic Innervation From the Basal Forebrain to the Visual Cortex in the Rat

    Directory of Open Access Journals (Sweden)

    Frédéric Huppé-Gourgues

    2018-03-01

    Full Text Available Acetylcholine is an important neurotransmitter for the regulation of visual attention, plasticity, and perceptual learning. It is released in the visual cortex predominantly by cholinergic projections from the basal forebrain, where stimulation may produce potentiation of visual processes. However, little is known about the fine organization of these corticopetal projections, such as whether basal forebrain neurons projecting to the primary and secondary visual cortical areas (V1 and V2, respectively are organized retinotopically. The aim of this study was to map these basal forebrain-V1/V2 projections. Microinjections of the fluorescent retrograde tracer cholera toxin b fragment in different sites within V1 and V2 in Long–Evans rats were performed. Retrogradely labeled cell bodies in the horizontal and vertical limbs of the diagonal band of Broca (HDB and VDB, respectively, nucleus basalis magnocellularis, and substantia innominata (SI, were mapped ex vivo with a computer-assisted microscope stage controlled by stereological software. Choline acetyltranferase immunohistochemistry was used to identify cholinergic cells. Our results showed a predominance of cholinergic projections coming from the HDB. These projections were not retinotopically organized but projections to V1 arised from neurons located in the anterior HDB/SI whereas projections to V2 arised from neurons located throughout the whole extent of HDB/SI. The absence of a clear topography of these projections suggests that BF activation can stimulate visual cortices broadly.

  12. MicroRNAs show mutually exclusive expression patterns in the brain of adult male rats

    DEFF Research Database (Denmark)

    Olsen, Line; Klausen, Mikkel; Helboe, Lone

    2009-01-01

    BACKGROUND: The brain is a major site of microRNA (miRNA) gene expression, but the spatial expression patterns of miRNAs within the brain have not yet been fully covered. METHODOLOGY/PRINCIPAL FINDINGS: We have characterized the regional expression profiles of miRNAs in five distinct regions...... of the adult rat brain: amygdala, cerebellum, hippocampus, hypothalamus and substantia nigra. Microarray profiling uncovered 48 miRNAs displaying more than three-fold enrichment between two or more brain regions. Notably, we found reciprocal expression profiles for a subset of the miRNAs predominantly found...... (> ten times) in either the cerebellum (miR-206 and miR-497) or the forebrain regions (miR-132, miR-212, miR-221 and miR-222). CONCLUSIONS/SIGNIFICANCE: The results indicate that some miRNAs could be important for area-specific functions in the brain. Our data, combined with previous studies in mice...

  13. Anatomical Inputs From the Sensory and Value Structures to the Tail of the Rat Striatum

    Directory of Open Access Journals (Sweden)

    Haiyan Jiang

    2018-05-01

    Full Text Available The caudal region of the rodent striatum, called the tail of the striatum (TS, is a relatively small area but might have a distinct function from other striatal subregions. Recent primate studies showed that this part of the striatum has a unique function in encoding long-term value memory of visual objects for habitual behavior. This function might be due to its specific connectivity. We identified inputs to the rat TS and compared those with inputs to the dorsomedial striatum (DMS in the same animals. The TS directly received anatomical inputs from both sensory structures and value-coding regions, but the DMS did not. First, inputs from the sensory cortex and sensory thalamus to the TS were found; visual, auditory, somatosensory and gustatory cortex and thalamus projected to the TS but not to the DMS. Second, two value systems innervated the TS; dopamine and serotonin neurons in the lateral part of the substantia nigra pars compacta (SNc and dorsal raphe nucleus projected to the TS, respectively. The DMS received inputs from the separate group of dopamine neurons in the medial part of the SNc. In addition, learning-related regions of the limbic system innervated the TS; the temporal areas and the basolateral amygdala selectively innervated the TS, but not the DMS. Our data showed that both sensory and value-processing structures innervated the TS, suggesting its plausible role in value-guided sensory-motor association for habitual behavior.

  14. Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat.

    Directory of Open Access Journals (Sweden)

    Bertrand Degos

    Full Text Available Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.

  15. Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.

    Science.gov (United States)

    Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F

    1987-12-01

    Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.

  16. Correlative single photon emission computed tomography imaging of [{sup 123}I]altropane binding in the rat model of Parkinson's

    Energy Technology Data Exchange (ETDEWEB)

    Gleave, Jacqueline A. [Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5 (Canada); Farncombe, Troy H.; Saab, Chantal [Department of Nuclear Medicine, Hamilton Health Sciences, Hamilton, Ontario, L8N 3Z5 (Canada); Doering, Laurie C., E-mail: doering@mcmaster.ca [Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5 (Canada)

    2011-07-15

    Introduction: This study used the dopamine transporter (DAT) probe, [{sup 123}I]-2{beta}-carbomethoxy-3{beta}-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane ([{sup 123}I]altropane), to assess the DAT levels in the 6-hydroxydopamine rat model of Parkinson's disease. We sought to assess if the right to left [{sup 123}I]altropane striatal ratios correlated with dopamine content in the striatum and substantia nigra and with behavioural outcomes. Methods: [{sup 123}I]altropane images taken pre- and postlesion were acquired before and after the transplantation of neural stem/progenitor cells. The images obtained using [{sup 123}I]altropane and single photon emission computed tomography (SPECT) were compared with specific behavioural tests and the dopamine content assessed by high-performance liquid chromatography. Results: [{sup 123}I]altropane binding correlated with the content of dopamine in the striatum; however, [{sup 123}I]altropane binding did not correlate with the dopamine content in the substantia nigra. There was a significant correlation of altropane ratios with the cylinder test and the postural instability test, but not with amphetamine rotations. The low coefficient of determination (r{sup 2}) for these correlations indicated that [{sup 123}I]altropane SPECT was not a good predictor of behavioural outcomes. Conclusion: Our data reveal that [{sup 123}I]altropane predicts the integrity of the striatal dopamine nerve terminals, but does not predict the integrity of the nigrostriatal system. [{sup 123}I]altropane could be a useful marker to measure dopamine content in cell replacement therapies; however, it would not be able to evaluate outcomes for neuroprotective strategies.

  17. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

    Science.gov (United States)

    Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane; Amalric, Marianne; Kerkerian-Le Goff, Lydia

    2015-01-01

    Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease.

  18. The mRNA expression and histological integrity in rat forebrain motor and sensory regions are minimally affected by acrylamide exposure through drinking water

    International Nuclear Information System (INIS)

    Bowyer, John F.; Latendresse, John R.; Delongchamp, Robert R.; Warbritton, Alan R.; Thomas, Monzy; Divine, Becky; Doerge, Daniel R.

    2009-01-01

    A study was undertaken to determine whether alterations in the gene expression or overt histological signs of neurotoxicity in selected regions of the forebrain might occur from acrylamide exposure via drinking water. Gene expression at the mRNA level was evaluated by cDNA array and/or RT-PCR analysis in the striatum, substantia nigra and parietal cortex of rat after a 2-week acrylamide exposure. The highest dose tested (maximally tolerated) of approximately 44 mg/kg/day resulted in a significant decreased body weight, sluggishness, and locomotor activity reduction. These physiological effects were not accompanied by prominent changes in gene expression in the forebrain. All the expression changes seen in the 1200 genes that were evaluated in the three brain regions were ≤ 1.5-fold, and most not significant. Very few, if any, statistically significant changes were seen in mRNA levels of the more than 50 genes directly related to the cholinergic, noradrenergic, GABAergic or glutamatergic neurotransmitter systems in the striatum, substantia nigra or parietal cortex. All the expression changes observed in genes related to dopaminergic function were less than 1.5-fold and not statistically significant and the 5HT1b receptor was the only serotonin-related gene affected. Therefore, gene expression changes were few and modest in basal ganglia and sensory cortex at a time when the behavioral manifestations of acrylamide toxicity had become prominent. No histological evidence of axonal, dendritic or neuronal cell body damage was found in the forebrain due to the acrylamide exposure. As well, microglial activation was not present. These findings are consistent with the absence of expression changes in genes related to changes in neuroinflammation or neurotoxicity. Over all, these data suggest that oral ingestion of acrylamide in drinking water or food, even at maximally tolerable levels, induced neither marked changes in gene expression nor neurotoxicity in the motor and

  19. Immunology taught by rats

    OpenAIRE

    Klenerman, P; Barnes, EJ

    2017-01-01

    Immunology may be best taught by viruses, and possibly by humans, but the rats of New York City surprisingly also have plenty to offer. A survey published in 2014 of the pathogens carried by rats trapped in houses and parks in Manhattan identified a huge burden of infectious agents in these animals, including several novel viruses. Among these are Norway rat hepaciviruses (NrHVs), which belong to the same family as hepatitis C virus (HCV). NrHVs were found in rat livers, raising the possibili...

  20. Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats.

    Science.gov (United States)

    Urakawa, S; Hida, H; Masuda, T; Misumi, S; Kim, T-S; Nishino, H

    2007-02-09

    Rats raised in an enriched environment (enriched rats) have been reported to show less motor dysfunction following brain lesions, but the neuronal correlates of this improvement have not been well clarified. The present study aimed to elucidate the effect of chemical brain lesions and environmental enrichment on motor function and lesion-induced neurogenesis. Three week-old, recently weaned rats were divided into two groups: one group was raised in an enriched environment and the other group was raised in a standard cage for 5 weeks. Striatal damage was induced at an age of 8 weeks by injection of the neuro-toxins 6-hydroxydopamine (6-OHDA) or quinolinic acid (QA) into the striatum, or by injection of 6-OHDA into the substantia nigra (SN), which depleted nigrostriatal dopaminergic innervation. Enriched rats showed better performance on beam walking compared with those raised in standard conditions, but both groups showed similar forelimb use asymmetry in a cylinder test. The number of bromodeoxyuridine-labeled proliferating cells in the subventricular zone was increased by a severe striatal lesion induced by QA injection 1 week after the lesion, but decreased by injection of 6-OHDA into the SN. Following induction of lesions by striatal injection of 6-OHDA or QA, the number of cells positive for doublecortin (DCX) was strongly increased in the striatum; however, there was no change in the number of DCX-positive cells following 6-OHDA injection into the SN. Environmental enrichment enhanced the increase of DCX-positive cells with migrating morphology in the dorsal striatum. In enriched rats, DCX-positive cells traversed the striatal parenchyma far from the corpus callosum and lateral ventricle. DCX-positive cells co-expressed an immature neuronal marker, polysialylated neural cell adhesion molecule, but were negative for a glial marker. These data suggest that environmental enrichment improves motor performance on beam walking and enhances neuronal migration toward

  1. Acetyl-L-Carnitine via Upegulating Dopamine D1 Receptor and Attenuating Microglial Activation Prevents Neuronal Loss and Improves Memory Functions in Parkinsonian Rats.

    Science.gov (United States)

    Singh, Sonu; Mishra, Akanksha; Srivastava, Neha; Shukla, Rakesh; Shukla, Shubha

    2018-01-01

    Parkinson's disease is accompanied by nonmotor symptoms including cognitive impairment, which precede the onset of motor symptoms in patients and are regulated by dopamine (DA) receptors and the mesocorticolimbic pathway. The relative contribution of DA receptors and astrocytic glutamate transporter (GLT-1) in cognitive functions is largely unexplored. Similarly, whether microglia-derived increased immune response affects cognitive functions and neuronal survival is not yet understood. We have investigated the effect of acetyl-L-carnitine (ALCAR) on cognitive functions and its possible underlying mechanism of action in 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats. ALCAR treatment in 6-OHDA-lesioned rats improved memory functions as confirmed by decreased latency time and path length in the Morris water maze test. ALCAR further enhanced D1 receptor levels without altering D2 receptor levels in the hippocampus and prefrontal cortex (PFC) regions, suggesting that the D1 receptor is preferentially involved in the regulation of cognitive functions. ALCAR attenuated microglial activation and release of inflammatory mediators through balancing proinflammatory and anti-inflammatory cytokines, which subsequently enhanced the survival of mature neurons in the CA1, CA3, and PFC regions and improved cognitive functions in hemiparkinsonian rats. ALCAR treatment also improved glutathione (GSH) content, while decreasing oxidative stress indices, inducible nitrogen oxide synthase (iNOS) levels, and astrogliosis resulting in the upregulation of GLT-1 levels. Additionally, ALCAR prevented the loss of dopaminergic (DAergic) neurons in ventral tagmental area (VTA)/substantia nigra pars compacta (SNpc) regions of 6-OHDA-lesioned rats, thus maintaining the integrity of the nigrostriatal pathway. Together, these results demonstrate that ALCAR treatment in hemiparkinsonian rats ameliorates neurodegeneration and cognitive deficits, hence suggesting its therapeutic potential in

  2. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

    Directory of Open Access Journals (Sweden)

    Tayra Judith

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  3. Striatal adenosine A2A receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [18F]-MRS5425

    International Nuclear Information System (INIS)

    Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit; Shinkre, Bidhan; Ma Ying; Niu Gang; Trenkle, William C.; Jacobson, Kenneth A.; Chen Xiaoyuan; Kiesewetter, Dale O.

    2011-01-01

    Introduction: A 2A receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an 18 F-labeled A 2A analog radiotracer ([ 18 F]-MRS5425) for A 2A receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A 2A receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [ 18 F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D 2 agonist quinpirole (1.0 mg/kg) or D 2 antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A 2A receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  4. Striatal adenosine A{sub 2A} receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [{sup 18}F]-MRS5425

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Shinkre, Bidhan [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Ma Ying [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Niu Gang [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Department of Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Trenkle, William C. [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Jacobson, Kenneth A. [Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Chen Xiaoyuan [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Kiesewetter, Dale O., E-mail: dk7k@nih.gov [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States)

    2011-08-15

    Introduction: A{sub 2A} receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an {sup 18}F-labeled A{sub 2A} analog radiotracer ([{sup 18}F]-MRS5425) for A{sub 2A} receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A{sub 2A} receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [{sup 18}F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D{sub 2} agonist quinpirole (1.0 mg/kg) or D{sub 2} antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A{sub 2A} receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  5. Dopamine depletion increases the power and coherence of high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

    Science.gov (United States)

    Ge, Shunnan; Yang, Chen; Li, Min; Li, Jiang; Chang, Xiaozan; Fu, Jian; Chen, Lei; Chang, Chongwang; Wang, Xuelian; Zhu, Junling; Gao, Guodong

    2012-07-17

    Studies on patients with Parkinson's disease and in animal models have observed enhanced synchronization of oscillations in several frequency bands within and between the cortical-basal ganglia (BG) structures. Recent research has also shown that synchronization of high-voltage spindles (HVSs) in the cortex, striatum and substantia nigra pars reticulate is increased by dopamine depletion. However, more evidence is needed to determine whether HVS activity in the whole cortex-BG network represents homologous alteration following dopamine depletion. As the globus pallidus (GP) is in a central position to propagate and synchronize oscillations in the cortical-BG circuits, we employed local-field potentials and electrocorticogram to simultaneously record oscillations in the GP and primary (M1) and secondary (M2) motor cortices on freely moving 6-hydroxydopamine (6-OHDA) lesioned and control rats. Results showed that HVS episodes recorded from GP, and M2 and M1 cortex areas were more numerous and longer in 6-OHDA lesioned rats compared to controls. Relative power associated with HVS activity in the GP, and M2 and M1 cortices of 6-OHDA lesioned rats was significantly greater than that for control rats. Coherence values for HVS activity between the GP, and M2 and M1 cortex areas were significantly increased by dopamine depletion. Time lag between the M1 cortex HVS and GP HVS was significantly shorter for dopamine depleted than normal rats. Findings indicate a crucial rule for dopamine in the regulation of HVS activity in the whole cortical-BG circuit, and suggest a close relationship between abnormally synchronized HVS oscillations in the cortex-BG network and Parkinson's disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Protective role of selenium and vitamins A, C and E against gamma irradiation-induced oxidative stress in diabetic rats

    International Nuclear Information System (INIS)

    Nagiub, N.I.; Abd El-maguid, A.; Saad, T.M.M.

    2006-01-01

    This study was designed to evaluate the protective effect of selenium and vitamins A, C and E on the oxidative stress in alloxan injected and/or irradiated rats. Rats were received a daily intraperitoneal administration of selenium (0.9 mg/rat) and vitamin A (14 IU/rat), vitamin C (0.8 mg/rat) and vitamin E (0.25 mg/rat) daily for one week before intraperitoneal injection with alloxan (60 mg/kg body weight) and/or gamma irradiation exposure (6.5 Gy). Animals were sacrificed on the tenth day post-irradiation and/or alloxan treatment. Histological examinations were made on eye tissue and blood was removed for biochemical analysis. The histological results obtained revealed that exposure to ionizing radiation or treatment with alloxan caused histopathological damage in the eye tissue manifested as a congestion in retinal blood capillaries, vacuolation in ganglionic cells and degeneration in nuclear cells of retina. The lens became coagulated, homogenous and oesinophilic while the cornea showed vacuolations in its epithelium, edema and hyalinosis of substantia propria.The biochemical results showed that exposure to single dose (6.5 Gy) of ionizing radiation or treatment with alloxan caused significant elevation in lipid peroxide content (MDA), glucose level, total cholesterol (TC), triacylglycerol (TAG), low density lipoprotein (LDL), accompanied with significant depletion in reduced glutathione content (GSH), superoxide dismutase (SOD) activity and high density lipoprotein (HDL) in blood samples. Administration of selenium and vitamin A, C and E before gamma radiation exposure and/or alloxan treatment exerted marked amelioration of the histological changes in the eye and of the biochemical changes in rats induced by radiation but did not ameliorate that due to alloxan treatment in the tested parameters, thus diminishing the magnitude of injury due to radiation only. According to the results obtained, it could be concluded that selenium and vitamin A, C and E (a

  7. RatMap—rat genome tools and data

    Science.gov (United States)

    Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M.; Ståhl, Fredrik

    2005-01-01

    The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB–Genetics at Göteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided. PMID:15608244

  8. SWEEP Project RAT

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Madsen, Søren; Petersen, L. B.

    This report presents the results from the design analyses made for the clustered suction caisson used as foundation for a Riser Access Tower (RAT). The RAT is intended built next to the K15-FA-1 Platform in the Dutch Sector of the North Sea....

  9. Colon of the rat

    International Nuclear Information System (INIS)

    Lindstroem, C.G.; Rosengren, J.-E.; Fork, F.-T.

    1979-01-01

    The anatomy and radiologic appearance of the colon in rats are described on the basis of 300 animals treated with carcinogenic agents and 40 normal rats. The macroscopic and microscopic appearance of the mucosa varies in the different parts of the colon. Lymphoid plaques are normal structures. The results justify a new anatomic nomenclature. (Auth.)

  10. Endoplasmic reticulum stress is involved in arsenite-induced oxidative injury in rat brain

    International Nuclear Information System (INIS)

    Lin, Anya M.Y.; Chao, P.L.; Fang, S.F.; Chi, C.W.; Yang, C.H.

    2007-01-01

    The mechanism underlying sodium arsenite (arsenite)-induced neurotoxicity was investigated in rat brain. Arsenite was locally infused in the substantia nigra (SN) of anesthetized rat. Seven days after infusion, lipid peroxidation in the infused SN was elevated and dopamine level in the ipsilateral striatum was reduced in a concentration-dependent manner (0.3-5 nmol). Furthermore, local infusion of arsenite (5 nmol) decreased GSH content and increased expression of heat shock protein 70 and heme oxygenase-1 in the infused SN. Aggregation of α-synuclein, a putative pathological protein involved in several CNS neurodegenerative diseases, was elevated in the arsenite-infused SN. From the breakdown pattern of α-spectrin, both necrosis and apoptosis were involved in the arsenite-induced neurotoxicity. Pyknotic nuclei, cellular shrinkage and cytoplasmic disintegration, indicating necrosis, and TUNEL-positive cells and DNA ladder, indicating apoptosis was observed in the arsenite-infused SN. Arsenite-induced apoptosis was mediated via two different organelle pathways, mitochondria and endoplasmic reticulum (ER). For mitochondrial activation, cytosolic cytochrome c and caspase-3 levels were elevated in the arsenite-infused SN. In ER pathway, arsenite increased activating transcription factor-4, X-box binding protein 1, C/EBP homologues protein (CHOP) and cytosolic immunoglobulin binding protein levels. Moreover, arsenite reduced procaspase 12 levels, an ER-specific enzyme in the infused SN. Taken together, our study suggests that arsenite is capable of inducing oxidative injury in CNS. In addition to mitochondria, ER stress was involved in the arsenite-induced apoptosis. Arsenite-induced neurotoxicity clinically implies a pathophysiological role of arsenite in CNS neurodegeneration

  11. Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

    International Nuclear Information System (INIS)

    Muck-Seler, Dorotea; Pivac, Nela; Diksic, Mirko

    2012-01-01

    Introduction: A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression. Methods: The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α- 14 C-methyl-L-tryptophan as a tracer. Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hour before the injection of the tracer (30 μCi). Results: There was no significant effect of fluvoxamine on plasma free tryptophan. After Benjamini–Hochberg False Discovery Rate correction, a significant decrease in the 5-HT synthesis rate in the fluvoxamine treated rats, was found in the raphe magnus (− 32%), but not in the median (− 14%) and dorsal (− 3%) raphe nuclei. In the regions with serotonergic axon terminals, significant increases in synthesis rates were observed in the dorsal (+ 41%) and ventral (+ 43%) hippocampus, visual (+ 38%), auditory (+ 65%) and parietal (+ 37%) cortex, and the substantia nigra pars compacta (+ 56%). There were no significant changes in the 5-HT synthesis rates in the median (+ 11%) and lateral (+ 24%) part of the caudate-putamen, nucleus accumbens (+ 5%), VTA (+ 16%) or frontal cortex (+ 6%). Conclusions: The data show that the acute administration of fluvoxamine affects 5-HT synthesis rates in a regionally specific pattern, with a general elevation of the synthesis in the terminal regions and a reduction in some cell body structures. The reasons for the regional specific effect of fluvoxamine on 5-HT synthesis are unclear, but may be mediated by the presynaptic serotonergic autoreceptors.

  12. Ketamine-induced oscillations in the motor circuit of the rat basal ganglia.

    Directory of Open Access Journals (Sweden)

    María Jesús Nicolás

    Full Text Available Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion.We recorded local field potentials from motor cortex, caudate-putamen (CPU, substantia nigra pars reticulata (SNr and subthalamic nucleus (STN in 20 awake rats before and after the administration of ketamine at three different subanesthetic doses (10, 25 and 50 mg/Kg, and saline as control condition. Motor behavior was semiautomatically quantified by custom-made software specifically developed for this setting.Ketamine induced coherent oscillations in low gamma (~ 50 Hz, high gamma (~ 80 Hz and high frequency (HFO, ~ 150 Hz bands, with different behavior in the four structures studied. While oscillatory activity at these three peaks was widespread across all structures, interactions showed a different pattern for each frequency band. Imaginary coherence at 150 Hz was maximum between motor cortex and the different basal ganglia nuclei, while low gamma coherence connected motor cortex with CPU and high gamma coherence was more constrained to the basal ganglia nuclei. Power at three bands correlated with the motor activity of the animal, but only coherence values in the HFO and high gamma range correlated with movement. Interactions in the low gamma band did not show a direct relationship to movement.These results suggest that the motor effects of ketamine administration may be primarily mediated by the induction of coherent widespread high-frequency activity in the motor circuit of the basal ganglia, together with a frequency

  13. Direct Effect of Remifentanil and Glycine Contained in Ultiva® on Nociceptive Transmission in the Spinal Cord: In Vivo and Slice Patch Clamp Analyses.

    Directory of Open Access Journals (Sweden)

    Makoto Sumie

    Full Text Available Ultiva® is commonly administered intravenously for analgesia during general anaesthesia and its main constituent remifentanil is an ultra-short-acting μ-opioid receptor agonist. Ultiva® is not approved for epidural or intrathecal use in clinical practice. Previous studies have reported that Ultiva® provokes opioid-induced hyperalgesia by interacting with spinal dorsal horn neurons. Ultiva® contains glycine, an inhibitory neurotransmitter but also an N-methyl-D-aspartate receptor co-activator. The presence of glycine in the formulation of Ultiva® potentially complicates its effects. We examined how Ultiva® directly affects nociceptive transmission in the spinal cord.We made patch-clamp recordings from substantia gelatinosa (SG neurons in the adult rat spinal dorsal horn in vivo and in spinal cord slices. We perfused Ultiva® onto the SG neurons and analysed its effects on the membrane potentials and synaptic responses activated by noxious mechanical stimuli.Bath application of Ultiva® hyperpolarized membrane potentials under current-clamp conditions and produced an outward current under voltage-clamp conditions. A barrage of excitatory postsynaptic currents (EPSCs evoked by the stimuli was suppressed by Ultiva®. Miniature EPSCs (mEPSCs were depressed in frequency but not amplitude. Ultiva®-induced outward currents and suppression of mEPSCs were not inhibited by the μ-opioid receptor antagonist naloxone, but were inhibited by the glycine receptor antagonist strychnine. The Ultiva®-induced currents demonstrated a specific equilibrium potential similar to glycine.We found that intrathecal administration of Ultiva® to SG neurons hyperpolarized membrane potentials and depressed presynaptic glutamate release predominantly through the activation of glycine receptors. No Ultiva®-induced excitatory effects were observed in SG neurons. Our results suggest different analgesic mechanisms of Ultiva® between intrathecal and intravenous

  14. Enhanced catecholaminergic and serotoninergic activity in rat brain from weaning to sexual maturity: rationale for prophylactic (-)deprenyl (selegiline) medication.

    Science.gov (United States)

    Knoll, J; Miklya, I

    1995-01-01

    Food deprived rats in the late developmental phase of life (2 months of age) are significantly more active than those in the early postdevelopmental phase (4 months of age), pointing to enhanced catecholaminergic activity during the developmental phase. We therefore measured the resting release of dopamine from the striatum, substantia nigra and tuberculum olfactorium, and of noradrenaline from the locus coeruleus, as an indicator of the basic activity of catecholaminergic neurons in the brain, in 2,4,8,16 and 32 weeks old male and female rats. We also measured the release of serotonin from the raphe. Both in male and female rats, the resting release of transmitters from brain catecholaminergic and serotoninergic neurons between weaning and the end of the 2nd month of age, i.e. during the crucial developmental phase of their life, was significantly higher than either before or after that period, signalling a transition from a developmental to a postdevelopmental (aging) phase of life and indicating that safe and effective measures are needed to maintain the catecholaminergic system at a higher activity level during the postdevelopmental phase. Daily administration of low doses (0.01-0.25 mg/kg) of (-)deprenyl for 21 days significantly enhances the resting release of catecholamines and diminishes that of serotonin, providing a rationale for prophylactic medication with this drug during the postdevelopmental lifespan. We also show that (-)methamphetamine, the parent compound of (-)deprenyl and (-)1-phenyl-2-propylaminopentane (PPAP), a deprenyl analogue free of MAO-B inhibitory potency but otherwise possessing the same pharmacological profile as (-)deprenyl, act similarly, furnishing direct evidence that enhancement of catecholaminergic activity in the brain by multiple, small dose administration of (-)deprenyl is unrelated to MAO-B inhibition.

  15. Amniotic fluid stem cells with low γ-interferon response showed behavioral improvement in Parkinsonism rat model.

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chang

    Full Text Available Amniotic fluid stem cells (AFSCs are multipotent stem cells that may be used in transplantation medicine. In this study, AFSCs established from amniocentesis were characterized on the basis of surface marker expression and differentiation potential. To further investigate the properties of AFSCs for translational applications, we examined the cell surface expression of human leukocyte antigens (HLA of these cells and estimated the therapeutic effect of AFSCs in parkinsonian rats. The expression profiles of HLA-II and transcription factors were compared between AFSCs and bone marrow-derived mesenchymal stem cells (BMMSCs following treatment with γ-IFN. We found that stimulation of AFSCs with γ-IFN prompted only a slight increase in the expression of HLA-Ia and HLA-E, and the rare HLA-II expression could also be observed in most AFSCs samples. Consequently, the expression of CIITA and RFX5 was weakly induced by γ-IFN stimulation of AFSCs compared to that of BMMSCs. In the transplantation test, Sprague Dawley rats with 6-hydroxydopamine lesioning of the substantia nigra were used as a parkinsonian-animal model. Following the negative γ-IFN response AFSCs injection, apomorphine-induced rotation was reduced by 75% in AFSCs engrafted parkinsonian rats but was increased by 53% in the control group after 12-weeks post-transplantation. The implanted AFSCs were viable, and were able to migrate into the brain's circuitry and express specific proteins of dopamine neurons, such as tyrosine hydroxylase and dopamine transporter. In conclusion, the relative insensitivity AFSCs to γ-IFN implies that AFSCs might have immune-tolerance in γ-IFN inflammatory conditions. Furthermore, the effective improvement of AFSCs transplantation for apomorphine-induced rotation paves the way for the clinical application in parkinsonian therapy.

  16. Protective Effects of Water Extract of Morus Nigra L. on 6-Hydroxydopamine Induced Parkinson’s Disease in Male Rats

    Directory of Open Access Journals (Sweden)

    Seyed Ali Ziai

    2018-01-01

    Full Text Available Background: Parkinson’s disease (PD is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is unknown, but major biochemical processes such as oxidative stress is largely described. Angiotensin II activates NADPH depending oxidases and produce superoxides formation. Morus nigra L. extract is an Angiotensin Converting Enzyme (ACE inhibitor and tested for anti-Parkinsonism effects by biochemical and behavioral evaluations.Materials and Methods: In total 48 Male Wistar rats weighting 200-250 g were divided into 4 groups: (1 Sham (normal saline was injected in the left SNC, (2 Neurotoxin (injection of 6-hydroxydopamine into left SNC, (3 Morus nigra L. aqueous extract and (4 captopril. Morus nigra (10 mg/kg and captopril (5 mg/kg were daily-injected i.p. from 6 days before neurotoxin injection, until one day after 6-hydroxydopamine injection. Muscle stiffness and apomorphine test were assessed in 6 rats of any groups after two weeks. Protein oxidation, lipid peroxidation and ACE activity were assessed in brains of 6 rats of each group after 24 hours.Results: Rotation test with apomorphine, Rigidity with Murprogo’s test, and lipid peroxidation in sham, captopril and Morus nigra groups were significantly lower than neurotoxin group. Protein oxidation in Morus nigra group was significantly lower than neurotoxin group. Brain ACE activity in neurotoxin, captopril and Morus nigra groups were inhibited.Conclusion: Morus nigra L. extract had protective effects on neuronal oxidation and death and improved signs of PD possibly by ACE inhibition.

  17. Protective role of acetylsalicylic acid (Aspirin) against gamma irradiation-induced ophthalmic and histological changes in rat's eye

    International Nuclear Information System (INIS)

    Naguib, N. I.; Abd El Maguid, A.

    2007-01-01

    Radiation generates a variety of free radicals during the exposure of biological tissues through radiolysis of water. These free radicals are highly reactive and cause oxidative damage to biological molecules. This study examined the protective ability of aspirin against radiation-induced ophthalmic and histological disorders in the eye of rats exposed to 6.5 Gy single dose of gamma irradiation, Acetylsalicylic acid was given daily to rats in drinking water (2.5 g/ L) 1 week pre-irradiation, during irradiation and 9 weeks post-irradiation. Experimental investigations showed that irradiation caused cataract formation. Irradiation also caused histopathological changes in the retina of the eyes described as focal degeneration and necrosis of the inner and outer nuclear layers, vacuolation of ganglionic cell layer as well as necrosis of retinal inner and outer segments of the rods and cones. The cornea revealed vacuolation of stratified epithelial layer, edema in substantia propria with dispersion of the connective tissue as well as presence of extravasated red blood cells as a result of exposure to radiation. The lens became homogenous and oesinophilic due to radiation exposure. The eye tissues of rats .that received acetylsalicylic acid supplement showed slight improvement of radiation-induced histological damage in the eyes and it also delayed the onset of cataract formation. According to the results obtained it could be concluded that oral administration of aspirin gave only a slight, nonsignificant reduction of eye radiation injury after exposure to single dose of gamma irradiation (6.5 Gy). The anatomy, physiology and biochemistry of the visual system make the eye uniquely vulnerable to damage from injurious agents, physical and chemical. Although many studies were conducted on a broad range of agents, the majority of all efforts are directed at deleterious effect of radiation on the eye tissues, and

  18. [123I]Epidepride neuroimaging of dopamine D2/D3 receptor in chronic MK-801-induced rat schizophrenia model

    International Nuclear Information System (INIS)

    Huang, Yuan-Ruei; Shih, Jun-Ming; Chang, Kang-Wei; Huang, Chieh; Wu, Yu-Lung; Chen, Chia-Chieh

    2012-01-01

    Purpose: [ 123 I]Epidepride is a radio-tracer with very high affinity for dopamine D 2 /D 3 receptors in brain. The importance of alteration in dopamine D 2 /D 3 receptor binding condition has been wildly verified in schizophrenia. In the present study we set up a rat schizophrenia model by chronic injection of a non-competitive NMDA receptor antagonist, MK-801, to examine if [ 123 I]epidepride could be used to evaluate the alterations of dopamine D 2 /D 3 receptor binding condition in specific brain regions. Method: Rats were given repeated injection of MK-801 (dissolved in saline, 0.3 mg/kg) or saline for 1 month. Afterwards, total distance traveled (cm) and social interaction changes were recorded. Radiochemical purity of [ 123 I]epidepride was analyzed by Radio-Thin-Layer Chromatography (chloroform: methanol, 9:1, v/v) and [ 123 I]epidepride neuroimages were obtained by ex vivo autoradiography and small animal SPECT/CT. Data obtained were then analyzed to determine the changes of specific binding ratio. Result: Chronic MK-801 treatment for a month caused significantly increased local motor activity and induced an inhibition of social interaction. As shown in [ 123 I]epidepride ex vivo autoradiographs, MK-801 induced a decrease of specific binding ratio in the striatum (24.01%), hypothalamus (35.43%), midbrain (41.73%) and substantia nigra (37.93%). In addition, [ 123 I]epidepride small animal SPECT/CT neuroimaging was performed in the striatum and midbrain. There were statistically significant decreases in specific binding ratio in both the striatum (P 123 I]epidepride is a useful radio-tracer to reveal the alterations of dopamine D 2 /D 3 receptor binding in a rat schizophrenia model and is also helpful to evaluate therapeutic effects of schizophrenia in the future.

  19. Improvement of spatial memory of male parkinsonian rats after treatment with adipose stem cells and rosemary leaf extract

    Directory of Open Access Journals (Sweden)

    Mahdieh Ramezanihossienabadi

    2018-01-01

    Full Text Available Background: Due to the neuroprotective effect of rosemary extract, this study aimed at examining the effect of co-treatment of adipose stem cells transplantation and the extract on memory disability of parkinsonian rats. Materials and Methods: In this experimental study, male parkinsonian rats were prepared by bilateral injection of 6-OHDA. The sham group was injected normal saline into the substantia nigra. The extract+medium group was gavaged with the extract 14 days before until 8 weeks after the injury, and the medium was intravenously injected. The extract+cell group was orally gavaged with the extract and the cells were injected. Morris water maze training was conducted one week before and after the lesion and also a retrieval test was performed 4 and 8 weeks after the lesion. Results: There was no significant difference in distance moved and escape latency at training days, before the injury, between the groups. However, a week after the injury, learning ability in lesioned animals was significantly decreased as compared to the sham group (P<0.05. Results of retention tests in four and eight weeks were similar. Duration of escape latency and time spent in target quadrant of lesioned rats were significantly increased and decreased respectively as compared to the sham (P<0.05. The extract+medium and extract+cell groups showed significant decrease and increase in escape latency and time spent in target quadrant as compared to the lesioned group (P<0.05, respectively. Conclusion: The cell therapy accompanied with orally administration of the rosemary extract can improve memory deficit in Parkinson’s disease.

  20. Intrastriatal injection of botulinum neurotoxin-A is not cytotoxic in rat brain - A histological and stereological analysis.

    Science.gov (United States)

    Mehlan, Juliane; Brosig, Hans; Schmitt, Oliver; Mix, Eilhard; Wree, Andreas; Hawlitschka, Alexander

    2016-01-01

    Parkinson's disease (PD) is caused by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in a deficiency of dopamine in the striatum and an increased release of acetylcholine by tonically active interneurons. Botulinum neurotoxin-A (BoNT-A) is well known for blocking transmitter release by cholinergic presynaptic terminals. Treating striatal hypercholinism by local application of BoNT-A could be a possible new local therapy option of PD. In previous studies of our group, we analyzed the effect of BoNT-A injection into the CPu of 6-OHDA lesioned hemiparkinsonian rats. Our studies showed that BoNT-A application in hemiparkinson rat model is capable of abolishing apomorphine induced rotations for approximately 3 months. Regularly occurring axonal swellings in the BoNT-A infiltrated striata were also discovered, which we named BoNT-A induced varicosities (BiVs). Résumé: Here we investigated the long-term effect of the injection of 1ng BoNT-A into the right CPu of naive Wistar rats on the number of ChAT-ir interneurons as well as on the numeric density and the volumetric size of the BiVs in the CPu. Significant differences in the number of ChAT-ir neurons between the right BoNT-A treated CPu and the left untreated CPu were not detected up to 12 month post BoNT-A injection. The numeric density of BiVs in the treated CPu reached a maximum 3 months after BoNT-A treatment and decreased afterwards, whereas the volume of single BiVs increased steadily throughout the whole time course of the experiment. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease

    International Nuclear Information System (INIS)

    Bennett, J.P. Jr.; Wooten, G.F.

    1986-01-01

    Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3 H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3 H-spiperone ( 3 H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3 H-SP in dopamine-denervated compared with intact striata. 3 H-SP in vivo binds to less than 10% of striatal sites labeled by 3 H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3 H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3 H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3 H-SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo-administered 3H-SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo

  2. Effect of thyrotropin-releasing hormone (TRH) on local cerebral glucose utilization, by the autoradiographic 2-deoxy [14C] glucose method, in conscious and pentobarbitalized rats

    International Nuclear Information System (INIS)

    Nagai, Y.; Narumi, S.; Nagawa, Y.; Sakurada, O.; Ueno, H.; Ishii, S.

    1980-01-01

    Effects of TRH and pentobarbital alone, and in combination, on local cerebral glucose utilization of rats were studied by the autoradiographic 2-deoxy[ 14 C] glucose method. TRH (5 mg/kg i.v.) reduced the rate of cerebral glucose utilization slightly in the whole brain. Locally, significant depression was observed in the following structures: frontal and visual cortices, hippocampus Ammon's horn and dentate gyrus, medial and lateral geniculate bodies, nucleus accumbens, caudate-putamen, substantia nigra, pontine gray matter, superior colliculus, superior olivary nucleus, vestibular nucleus, lateral lemniscus and cerebellar cortex. Pentobarbital (30 mg/kg i.v.) produced a marked and diffuse reduction in the rate of glucose utilization throughout the brain. TRH given 15 min after the administration of pentobarbital markedly shortened the pentobarbital sleeping time and caused some reversal of the depression in local cerebral glucose utilization produced by pentobarbital., These effects were almost completely abolished by pretreatment with intracerebroventricular injection of atropine methyl bromide (20 μg/rat). These results indicate that although TRH acts to cause a reduction in the rate of cerebral glucose utilization, it reverses the depression induced by pentobarbital, via a cholinergic mechanism, in a number of structures, some of which are related to monoaminergic systems and the reticulo-thalamo-cortical activating system. (author)

  3. Endothelial Proliferation and Increased Blood - Brain Barrier Permeability in the Basal Ganglia in a Rat Model of 3,4-Dihydrozyphenyl-L-Alanine-Induced Dyskinesia

    DEFF Research Database (Denmark)

    Westin, Jenny E.; Lindgren, Hanna S.; Gardi, Jonathan Eyal

    2006-01-01

    3,4-Dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia is associated with molecular and synaptic plasticity in the basal ganglia, but the occurrence of structural remodeling through cell genesis has not been explored. In this study, rats with 6-hydroxydopamine lesions received injections of th...... of angiogenesis and blood-brain barrier dysfunction in an experimental model of L-DOPA-induced dyskinesia. These microvascular changes are likely to affect the kinetics of L-DOPA entry into the brain, favoring the occurrence of motor complications....... dyskinesia. The vast majority (60-80%) of the newborn cells stained positively for endothelial markers. This endothelial proliferation was associated with an upregulation of immature endothelial markers (nestin) and a downregulation of endothelial barrier antigen on blood vessel walls. In addition......, dyskinetic rats exhibited a significant increase in total blood vessel length and a visible extravasation of serum albumin in the two structures in which endothelial proliferation was most pronounced (substantia nigra pars reticulata and entopeduncular nucleus). The present study provides the first evidence...

  4. Application of the Physical Disector Principle for Quantification of Dopaminergic Neuronal Loss in a Rat 6-Hydroxydopamine Nigral Lesion Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Katrine Fabricius

    2017-12-01

    Full Text Available Stereological analysis is the optimal tool for quantitative assessment of brain morphological and cellular changes induced by neurotoxic lesions or treatment interventions. Stereological methods based on random sampling techniques yield unbiased estimates of particle counts within a defined volume, thereby providing a true quantitative estimate of the target cell population. Neurodegenerative diseases involve loss of specific neuron types, such as the midbrain tyrosine hydroxylase-positive dopamine neurons in Parkinson's disease and in animal models of nigrostriatal degeneration. Therefore, we applied an established automated physical disector principle in a fractionator design for efficient stereological quantitative analysis of tyrosine hydroxylase (TH-positive dopamine neurons in the substantia nigra pars compacta of hemiparkinsonian rats with unilateral 6-hydroxydopamine (6-OHDA lesions. We obtained reliable estimates of dopamine neuron numbers, and established the relationship between behavioral asymmetry and dopamine neuron loss on the lesioned side. In conclusion, the automated physical disector principle provided a useful and efficient tool for unbiased estimation of TH-positive neurons in rat midbrain, and should prove valuable for investigating neuroprotective strategies in 6-OHDA model of parkinsonism, while generalizing to other immunohistochemically-defined cell populations.

  5. The transfection of BDNF to dopamine neurons potentiates the effect of dopamine D3 receptor agonist recovering the striatal innervation, dendritic spines and motor behavior in an aged rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Luis F Razgado-Hernandez

    Full Text Available The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson's disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT administered i.p. during 4½ months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old, immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy

  6. Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence.

    Science.gov (United States)

    Cadoni, Cristina; Pisanu, Augusta; Simola, Nicola; Frau, Lucia; Porceddu, Pier Francesca; Corongiu, Silvia; Dessì, Christian; Sil, Annesha; Plumitallo, Antonio; Wardas, Jadwiga; Di Chiara, Gaetano

    2017-09-01

    Although MDMA (3,4-methylendioxymethamphetamine, ecstasy) neurotoxicity in serotonin neurons is largely recognized in a wide variety of species including man, neurotoxicity in dopamine (DA) neurons is thought to be species-specific. MDMA is mainly consumed by adolescents, often in conjunction with caffeine (Energy Drinks) and this association has been reported to exacerbate MDMA toxic effects. In order to model these aspects of MDMA use, vis-à-vis their impact on DA neurons, we investigated the effects of adolescent exposure to low doses of MDMA (5 mg/kg for 10 days), alone or in combination with caffeine (10 mg/kg) on neuronal and functional DA indices and on recognition memory in adult rats. MDMA reduced density of tyrosine hydroxylase (TH) positive neurons in the ventral tegmental area and in the substantia nigra pars compacta, and immunoreactivity of TH and DA transporter in the nucleus accumbens (NAc) shell and core, and caudate-putamen. This same treatment caused a reduction of basal dialysate DA in the NAc core. MDMA-pretreated rats also showed behavioral sensitization to a MDMA challenge at adulthood and potentiation of MDMA-induced increase of dialysate DA in the NAc core, but not in the NAc shell. In addition, MDMA-treated rats displayed a deficit in recognition memory. Caffeine co-administration did not affect the above outcomes. Our results show that adolescent exposure of rats to low doses of MDMA induces long-lasting and widespread reduction of DA neurons indicative of a neurotoxic effect on DA neurons and suggestive of a degeneration of the same neurons. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Individually reared rats

    International Nuclear Information System (INIS)

    Kraeuchi, K.; Gentsch, C.; Feer, H.

    1981-01-01

    The influence of social isolation in rats on postsynaptic alpha 1 - and beta-adrenergic receptors, on the cAMP generating system and on the presynaptic uptake mechanism in the central noradrenergic system was examined in different brain regions. Rearing rats in isolation from the 19th day of life for 12 weeks leads in all regions to a general tendency for a reduction in 3 H-DHA binding, to an enhanced 3 H-WB4101 binding and to a decreased responsiveness of the noradrenaline sensitive cAMP generating system. These changes reach significance only in the pons-medulla-thallamusregion. Isolated rats showed an increased synaptosomal uptake of noradrenaline, most pronounced and significant in the hypothalamus. Our data provide further support for a disturbance in central noradrenergic function in isolated rats. (author)

  8. Impact of L-DOPA treatment on regional cerebral blood flow and metabolism in the basal ganglia in a rat model of Parkinson's disease.

    Science.gov (United States)

    Ohlin, K Elisabet; Sebastianutto, Irene; Adkins, Chris E; Lundblad, Cornelia; Lockman, Paul R; Cenci, M Angela

    2012-05-15

    Large increases in regional cerebral blood flow (rCBF) have been measured in patients with Parkinson's disease (PD) following the administration of L-DOPA, but the underlying mechanisms have remained unknown. In this study, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were used to compare patterns of rCBF and regional cerebral glucose utilisation (rCGU) in chronically L-DOPA-treated subjects following a final injection of L-DOPA or saline. The same animal model was used to the leakage of a blood-brain barrier (BBB) tracer molecule at 60 min vs. 24h following the last L-DOPA injection of a chronic treatment. All the parameters under investigation were examined with brain autoradiography following intravenous injections of specific radiotracers in awake animals ([14C]-iodoantipyrine for rCBF, [14C]-2-deoxyglucose for rCGU, and [14C]-α-aminoisobutyric acid for BBB leakage). Significant changes in rCBF and rCGU on the side ipsilateral to the 6-OHDA lesion relative to the non-lesioned side were seen at 60 min ("ON") but not 24h ("OFF") following L-DOPA administration. These changes were not seen in sham-operated rats. In the output nuclei of the basal ganglia (the entopeduncular nucleus and the substantia nigra pars reticulata) both rCBF and rCGU were elevated both in acutely L-DOPA-treated rats and chronically L-DOPA-treated rats displaying dyskinesia, but did not change significantly in chronically L-DOPA-treated non-dyskinetic cases. Acutely and chronically L-DOPA-treated rats with dyskinesia exhibited increases in rCBF "ON L-DOPA" also in the motor cortex, the striatum, and the globus pallidus, but the corresponding changes in rCGU did not show the same direction, magnitude, and/or relative group differences. The uptake of a BBB tracer (studied in the striatum and the substantia nigra reticulata in chronically L-DOPA treated rats) was significantly higher ON vs. OFF L-DOPA. The present results are the first to show that the administration of L-DOPA is

  9. Developmental Vitamin D (DVD) Deficiency Reduces Nurr1 and TH Expression in Post-mitotic Dopamine Neurons in Rat Mesencephalon.

    Science.gov (United States)

    Luan, Wei; Hammond, Luke Alexander; Cotter, Edmund; Osborne, Geoffrey William; Alexander, Suzanne Adele; Nink, Virginia; Cui, Xiaoying; Eyles, Darryl Walter

    2018-03-01

    Developmental vitamin D (DVD) deficiency has been proposed as an important risk factor for schizophrenia. Our previous study using Sprague Dawley rats found that DVD deficiency disrupted the ontogeny of mesencephalic dopamine neurons by decreasing the mRNA level of a crucial differentiation factor of dopamine cells, the nuclear receptor related 1 protein (Nurr1). However, it remains unknown whether this reflects a reduction in dopamine cell number or in Nurr1 expression. It is also unclear if any particular subset of developing dopamine neurons in the mesencephalon is selectively affected. In this study, we employed state-of-the-art spinning disk confocal microscopy optimized for the imaging of tissue sections and 3D segmentation to assess post-mitotic dopamine cells on a single-cell basis in the rat mesencephalon at embryonic day 15. Our results showed that DVD deficiency did not alter the number, morphology, or positioning of post-mitotic dopamine cells. However, the ratio of Nurr1+TH+ cells in the substantia nigra pars compacta (SNc) compared with the ventral tegmental area (VTA) was increased in DVD-deficient embryos. In addition, the expression of Nurr1 in immature dopamine cells and mature dopamine neurons in the VTA was decreased in DVD-deficient group. Tyrosine hydroxylase was selectively reduced in SNc of DVD-deficient mesencephalon. We conclude that DVD deficiency induced early alterations in mesencephalic dopamine development may in part explain the abnormal dopamine-related behaviors found in this model. Our findings may have broader implications for how certain environmental risk factors for schizophrenia may shape the ontogeny of dopaminergic systems and by inference increase the risk of schizophrenia.

  10. 14C-dopamine microinjected into the brain-stem of the rat: dispersion kinetics, site content and functional dose

    International Nuclear Information System (INIS)

    Myers, R.D.; Hoch, D.B.

    1978-01-01

    A morphological analysis was undertaken of both the dispersion characteristics and tissue content of dopamine (DA) microinjected acutely into the brain-stem of the anesthetized rat. 14C-DA, with a specific activity of 56-62 mCi/mMol, was infused unilaterally into the pars compacta of the substantia nigra in one of four test volumes: 0.5, 1.0, 4.0 or 8.0 microliters. The concentration of the 14C-DA solution was 1.0 microCi/microliter, equivalent to 3.01 micrograms/microliters, which was delivered at an injection rate of 1.0 microliter per 45 sec. At an interval of either one min or 15 min following the microinjection, the rat's brain was removed rapidly from its calvarium, flash frozen and then cut in the coronal plane on a freezing microtome in 500 micron slabs. After each of the respective serial slabs was mounted on glass, the Eik Nes-Brizzee trochar technique for the discrete removal of tissue samples was used to obtain 0.5 mm dia. cylindrical plugs of meso-diencephalic tissue at distances from the site of injection ranging from 0.5 to 2.5 mm, center to center. Each sample plug was subsequently solubilized and 14C-DA activity quantitated by liquid scintillation spectrometry. The results show that regardless of volume, the spatial patterning of the microinjected solution assumes a tear-drop or pear shape, not a sphere. Further, as the volume of the injection is increased from 0.5 to 8.0 microliters, the magnitude of the dispersion of 14C-DA is enhanced throughout the surrounding parenchyma, but not in a linear fashion

  11. Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain.

    Science.gov (United States)

    Kim, Youngsoo; Elmenhorst, David; Weisshaupt, Angela; Wedekind, Franziska; Kroll, Tina; McCarley, Robert W; Strecker, Robert E; Bauer, Andreas

    2015-10-01

    Although chronic sleep restriction frequently produces long-lasting behavioural and physiological impairments in humans, the underlying neural mechanisms are unknown. Here we used a rat model of chronic sleep restriction to investigate the role of brain adenosine and noradrenaline systems, known to regulate sleep and wakefulness, respectively. The density of adenosine A1 and A2a receptors and β-adrenergic receptors before, during and following 5 days of sleep restriction was assessed with autoradiography. Rats (n = 48) were sleep-deprived for 18 h day(-1) for 5 consecutive days (SR1-SR5), followed by 3 unrestricted recovery sleep days (R1-R3). Brains were collected at the beginning of the light period, which was immediately after the end of sleep deprivation on sleep restriction days. Chronic sleep restriction increased adenosine A1 receptor density significantly in nine of the 13 brain areas analysed with elevations also observed on R3 (+18 to +32%). In contrast, chronic sleep restriction reduced adenosine A2a receptor density significantly in one of the three brain areas analysed (olfactory tubercle which declined 26-31% from SR1 to R1). A decrease in β-adrenergic receptors density was seen in substantia innominata and ventral pallidum which remained reduced on R3, but no changes were found in the anterior cingulate cortex. These data suggest that chronic sleep restriction can induce long-term changes in the brain adenosine and noradrenaline receptors, which may underlie the long-lasting neurocognitive impairments observed in chronic sleep restriction. © 2015 European Sleep Research Society.

  12. Prenatal ethanol exposure modifies locomotor activity and induces selective changes in Met-enk expression in adolescent rats.

    Science.gov (United States)

    Abate, P; Reyes-Guzmán, A C; Hernández-Fonseca, K; Méndez, M

    2017-04-01

    Several studies suggest that prenatal ethanol exposure (PEE) facilitates ethanol intake. Opioid peptides play a main role in ethanol reinforcement during infancy and adulthood. However, PEE effects upon motor responsiveness elicited by an ethanol challenge and the participation of opioids in these actions remain to be understood. This work assessed the susceptibility of adolescent rats to prenatal and/or postnatal ethanol exposure in terms of behavioral responses, as well as alcohol effects on Met-enk expression in brain areas related to drug reinforcement. Motor parameters (horizontal locomotion, rearings and stereotyped behaviors) in pre- and postnatally ethanol-challenged adolescents were evaluated. Pregnant rats received ethanol (2g/kg) or water during gestational days 17-20. Adolescents at postnatal day 30 (PD30) were tested in a three-trial activity paradigm (habituation, vehicle and drug sessions). Met-enk content was quantitated by radioimmunoassay in several regions: ventral tegmental area [VTA], nucleus accumbens [NAcc], prefrontal cortex [PFC], substantia nigra [SN], caudate-putamen [CP], amygdala, hypothalamus and hippocampus. PEE significantly reduced rearing responses. Ethanol challenge at PD30 decreased horizontal locomotion and showed a tendency to reduce rearings and stereotyped behaviors. PEE increased Met-enk content in the PFC, CP, hypothalamus and hippocampus, but did not alter peptide levels in the amygdala, VTA and NAcc. These findings suggest that PEE selectively modifies behavioral parameters at PD30 and induces specific changes in Met-enk content in regions of the mesocortical and nigrostriatal pathways, the hypothalamus and hippocampus. Prenatal and postnatal ethanol actions on motor activity in adolescents could involve activation of specific neural enkephalinergic pathways. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Formation of multinucleated giant cells and microglial degeneration in rats expressing a mutant Cu/Zn superoxide dismutase gene

    Directory of Open Access Journals (Sweden)

    Streit Wolfgang J

    2007-02-01

    Full Text Available Abstract Background Microglial neuroinflammation is thought to play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS. The purpose of this study was to provide a histopathological evaluation of the microglial neuroinflammatory response in a rodent model of ALS, the SOD1G93A transgenic rat. Methods Multiple levels of the CNS from spinal cord to cerebral cortex were studied in SOD1G93A transgenic rats during three stages of natural disease progression, including presymptomatic, early symptomatic (onset, and late symptomatic (end stage, using immuno- and lectin histochemical markers for microglia, such as OX-42, OX-6, and Griffonia simplicifolia isolectin B4. Results Our studies revealed abnormal aggregates of microglia forming in the spinal cord as early as the presymptomatic stage. During the symptomatic stages there was prominent formation of multinucleated giant cells through fusion of microglial cells in the spinal cord, brainstem, and red nucleus of the midbrain. Other brain regions, including substantia nigra, cranial nerve nuclei, hippocampus and cortex showed normal appearing microglia. In animals during end stage disease at 4–5 months of age virtually all microglia in the spinal cord gray matter showed extensive fragmentation of their cytoplasm (cytorrhexis, indicative of widespread microglial degeneration. Few microglia exhibiting nuclear fragmentation (karyorrhexis indicative of apoptosis were identified at any stage. Conclusion The current findings demonstrate the occurrence of severe abnormalities in microglia, such as cell fusions and cytorrhexis, which may be the result of expression of mutant SOD1 in these cells. The microglial changes observed are different from those that accompany normal microglial activation, and they demonstrate that aberrant activation and degeneration of microglia is part of the pathogenesis of motor neuron disease.

  14. Alteration of striatal dopamine levels under various partial pressure of oxygen in pre-convulsive and convulsive phases in freely-moving rats.

    Science.gov (United States)

    Lavoute, Cécile; Weiss, Michel; Risso, Jean-Jacques; Rostain, Jean-Claude

    2014-02-01

    The purpose of this study was to investigate the change in the striatal dopamine (DA) level in freely-moving rat exposed to different partial pressure of oxygen (from 1 to 5 ATA). Some works have suggested that DA release by the substantia nigra pars compacta (SNc) neurons in the striatum could be disturbed by hyperbaric oxygen (HBO) exposure, altering therefore the basal ganglia activity. Such changes could result in a change in glutamatergic and GABAergic control of the dopaminergic neurons into the SNc. Such alterations could provide more information about the oxygen-induced seizures observed at 5 ATA in rat. DA-sensitive electrodes were implanted into the striatum under general anesthesia. After 1 week rest, awaked rats were exposed to oxygen-nitrogen mixture at a partial pressure of oxygen of 1, 2, 3, 4 and 5 ATA. DA level was monitored continuously (every 3 min) by in vivo voltammetry before and during HBO exposure. HBO induced a decrease in DA level in relationship to the increase in partial pressure of oxygen from 1 ATA to 4 ATA (-15 % at 1 ATA, -30 % at 2 ATA, -40 % at 3 ATA, -45 % at 4 ATA), without signs of oxygen toxicity. At 5 ATA, DA level strongly decreases (-75 %) before seizure which occurred after 27 min ± 7 HBO exposure. After the epileptic seizure the decrease in DA level disappeared. These changes and the biphasic effect of HBO were discussed in function of HBO action on neurochemical regulations of the nigro striatal pathway.

  15. α-Synuclein-induced dopaminergic neurodegeneration in a rat model of Parkinson's disease occurs independent of ATP13A2 (PARK9).

    Science.gov (United States)

    Daniel, Guillaume; Musso, Alessandra; Tsika, Elpida; Fiser, Aris; Glauser, Liliane; Pletnikova, Olga; Schneider, Bernard L; Moore, Darren J

    2015-01-01

    Mutations in the ATP13A2 (PARK9) gene cause early-onset, autosomal recessive Parkinson's disease (PD) and Kufor-Rakeb syndrome. ATP13A2 mRNA is spliced into three distinct isoforms encoding a P5-type ATPase involved in regulating heavy metal transport across vesicular membranes. Here, we demonstrate that three ATP13A2 mRNA isoforms are expressed in the normal human brain and are modestly increased in the cingulate cortex of PD cases. ATP13A2 can mediate protection toward a number of stressors in mammalian cells and can protect against α-synuclein-induced toxicity in cellular and invertebrate models of PD. Using a primary cortical neuronal model combined with lentiviral-mediated gene transfer, we demonstrate that human ATP13A2 isoforms 1 and 2 display selective neuroprotective effects toward toxicity induced by manganese and hydrogen peroxide exposure through an ATPase-independent mechanism. The familial PD mutations, F182L and G504R, abolish the neuroprotective effects of ATP13A2 consistent with a loss-of-function mechanism. We further demonstrate that the AAV-mediated overexpression of human ATP13A2 is not sufficient to attenuate dopaminergic neurodegeneration, neuropathology, and striatal dopamine and motoric deficits induced by human α-synuclein expression in a rat model of PD. Intriguingly, the delivery of an ATPase-deficient form of ATP13A2 (D513N) to the substantia nigra is sufficient to induce dopaminergic neuronal degeneration and motor deficits in rats, potentially suggesting a dominant-negative mechanism of action. Collectively, our data demonstrate a distinct lack of ATP13A2-mediated protection against α-synuclein-induced neurotoxicity in the rat nigrostriatal dopaminergic pathway, and limited neuroprotective capacity overall, and raise doubts about the potential of ATP13A2 as a therapeutic target for PD. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Pramipexole but not imipramine or fluoxetine reverses the "depressive-like" behaviour in a rat model of preclinical stages of Parkinson's disease.

    Science.gov (United States)

    Berghauzen-Maciejewska, Klemencja; Kuter, Katarzyna; Kolasiewicz, Wacław; Głowacka, Urszula; Dziubina, Anna; Ossowska, Krystyna; Wardas, Jadwiga

    2014-09-01

    Depression is a frequent comorbid disorder in Parkinson's disease and may antedate its motor symptoms. However, mechanisms underlying Parkinson's disease-associated depression are unknown and its current medication is insufficient. The aim of the present study was to compare antidepressant-like effects of imipramine, fluoxetine and pramipexole in a model of preclinical stages of Parkinson's disease in rats. 6-Hydroxydopamine was bilaterally injected into the ventrolateral region of the caudate-putamen in rats. This treatment induced moderate decreases in the levels of dopamine and its metabolites in the caudate-putamen, nucleus accumbens and frontal cortex and reduced the density of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta and ventral tegmental area. The lesion increased immobility measured in the forced swimming test without influencing locomotor activity. Chronic (13 days) administration of pramipexole (1mg/kg sc/twice a day) reversed prolongation of the immobility time in lesioned animals but did not stimulate their locomotion. Chronic pramipexole activated dopaminergic transmission in the brain structures which might contribute to its effectiveness in the forced swimming test. In contrast, the 13-day administration of imipramine (10mg/kg ip/day) and fluoxetine (10mg/kg ip/day) did not shorten the immobility time in lesioned rats but reduced their locomotion. The present study indicates that already a moderate lesion of dopaminergic neurons induces "depressive-like" behaviour in animals which is reversed by chronic administration of the antiparkinsonian drug, pramipexole. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Structure of the vitreoretinal border region in spontaneously hypertensive rats (SHR rats)

    DEFF Research Database (Denmark)

    Heegaard, Steffen

    1993-01-01

    Øjenpatologi, vitreoretinal border region, inner limiting membrane of the retina, spontaneously hypertensive rats, SHR rats, ultrastructure......Øjenpatologi, vitreoretinal border region, inner limiting membrane of the retina, spontaneously hypertensive rats, SHR rats, ultrastructure...

  18. The neurotoxic effects of prenatal gabapentin and oxcarbazepine exposure on newborn rats.

    Science.gov (United States)

    Erisgin, Zuleyha; Ayas, Bulent; Nyengaard, Jens R; Ercument Beyhun, N; Terzi, Yuksel

    2017-10-05

    Teratogenicity is a problematic issue for pregnant women because of X-ray radiation, drugs, and genetic and unknown variables. First-generation antiepileptic drugs (AED) like valproic acid are well-known teratogens for developing fetuses. However, their usage is necessary in order to prevent maternal seizures. The underlying mechanism of birth defects associated with AED exposure remains unclear and information about the neurotoxic effects of prenatal exposure to AED is still limited. Oxcarbazepine (OXC) and gabapentin (GBP) are second-generation AED. It still remains unclear how much these drugs are safe during pregnancy. This study aimed to investigate whether any neurotoxic effect of OXC and GBP in utero exposure on the developing brain. Eighteen pregnant Wistar albino rats were divided into six groups. The first group was exposed to OXC at 100 mg/kg/day, the second to GBP at 50 mg/kg/day, and third to saline (0.9% NaCl) at 1.5 ml/day between the first and the fifth days of gestation. The same procedure was applied at the same dosages between the 6th and the 15th days of gestation for the 2nd three groups. Five female offspring (total n = 30, 45 days old) were taken from each group and stereological methods were applied in order to analyze the total and dopaminergic neuron number of the substantia nigra pars compacta (SNc). The result is that the OXC and GBP exposure at different gestational periods may not give rise to congenital malformation and it appears that the GBP exposure during the organogenesis period proliferatively affects the total number of neurons.

  19. Aged Lewis rats exposed to low and moderate doses of rotenone are a good model for studying the process of protein aggregation and its effects upon central nervous system cell physiology

    Directory of Open Access Journals (Sweden)

    Michael F. Almeida

    Full Text Available ABSTRACT Cell physiology is impaired before protein aggregation and this may be more relevant than inclusions themselves for neurodegeneration. The present study aimed to characterize an animal model to enable the analysis of the cell biology before and after protein aggregation. Ten-month-old Lewis rats were exposed either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini-pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta peptide and protein carbonylation (indicative of oxidative stress were evaluated in the hippocampus, substantia nigra and locus coeruleus through immunohistochemistry or western blot. It was found that 2 mg/kg/day rotenone increased amyloid-beta peptide, hyperphosphorylation of TAU and alpha-synuclein. Rotenone at 1mg/kg/day did not alter protein levels. Protein carbonylation remained unchanged. This study demonstrated that aged Lewis rats exposed to a low dose of rotenone is a useful model to study cellular processes before protein aggregation, while the higher dose makes a good model to study the effects of protein inclusions.

  20. Rat bite fever.

    NARCIS (Netherlands)

    Gaastra, W.; Boot, R.G.A.; Ho, H.; Lipman, L.J.A.

    2009-01-01

    Rat bite fever (RBF) is a bacterial zoonosis for which two causal bacterial species have been identified: Streptobacillis moniliformis and Spirillum minus. Haverhill fever (HF) is a form of S. moniliformis infection believed to develop after ingestion of contaminated food or water. Here the

  1. Anti-human α-synuclein N-terminal peptide antibody protects against dopaminergic cell death and ameliorates behavioral deficits in an AAV-α-synuclein rat model of Parkinson's disease.

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    Md Shahaduzzaman

    Full Text Available The protein α-synuclein (α-Syn has a central role in the pathogenesis of Parkinson's disease (PD and immunotherapeutic approaches targeting this molecule have shown promising results. In this study, novel antibodies were generated against specific peptides from full length human α-Syn and evaluated for effectiveness in ameliorating α-Syn-induced cell death and behavioral deficits in an AAV-α-Syn expressing rat model of PD. Fisher 344 rats were injected with rAAV vector into the right substantia nigra (SN, while control rats received an AAV vector expressing green fluorescent protein (GFP. Beginning one week after injection of the AAV-α-Syn vectors, rats were treated intraperitoneally with either control IgG or antibodies against the N-terminal (AB1, or central region (AB2 of α-Syn. An unbiased stereological estimation of TH+, NeuN+, and OX6 (MHC-II immunostaining revealed that the α-Syn peptide antibodies (AB1 and AB2 significantly inhibited α-Syn-induced dopaminergic cell (DA and NeuN+ cell loss (one-way ANOVA (F (3, 30 = 5.8, p = 0.002 and (F (3, 29 = 7.92, p = 0.002 respectively, as well as decreasing the number of activated microglia in the ipsilateral SN (one-way ANOVA F = 14.09; p = 0.0003. Antibody treated animals also had lower levels of α-Syn in the ipsilateral SN (one-way ANOVA F (7, 37 = 9.786; p = 0.0001 and demonstrated a partial intermediate improvement of the behavioral deficits. Our data suggest that, in particular, an α-Syn peptide antibody against the N-terminal region of the protein can protect against DA neuron loss and, to some extent behavioral deficits. As such, these results may be a potential therapeutic strategy for halting the progression of PD.

  2. AAV-mediated gene transfer of the obesity-associated gene Etv5 in rat midbrain does not affect energy balance or motivated behavior.

    Directory of Open Access Journals (Sweden)

    Arjen J Boender

    Full Text Available Several genome-wide association studies have implicated the transcription factor E-twenty- six version 5 (Etv5 in the regulation of body mass index. Further substantiating the role of Etv5 in feeding behavior are the findings that targeted disruption of Etv5 in mice leads to decreased body weight gain and that expression of Etv5 is decreased in the ventral tegmental area and substantia nigra pars compacta (VTA/SNpc after food restriction. As Etv5 has been suggested to influence dopaminergic neurotransmission by driving the expression of genes that are responsible for the synthesis and release of dopamine, we investigated if expression levels of Etv5 are dependent on nutritional state and subsequently influence the expression levels of tyrosine hydroxylase. While it was shown that Etv5 expression in the VTA/SNpc increases after central administration of leptin and that Etv5 was able to drive expression of tyrosine hydroxylase in vitro, AAV-mediated gene transfer of Etv5 into the VTA/SNpc of rats did not alter expression of tyrosine hydroxylase in vivo. Moreover, AAV-mediated gene transfer of Etv5 in the VTA/SNpc did not affect measures of energy balance or performances in a progressive ratio schedule. Thus, these data do not support a role for increased expression of Etv5 in the VTA/SNpc in the regulation of feeding behavior.

  3. Laughing rats are optimistic.

    Directory of Open Access Journals (Sweden)

    Rafal Rygula

    Full Text Available Emotions can bias human decisions- for example depressed or anxious people tend to make pessimistic judgements while those in positive affective states are often more optimistic. Several studies have reported that affect contingent judgement biases can also be produced in animals. The animals, however, cannot self-report; therefore, the valence of their emotions, to date, could only be assumed. Here we present the results of an experiment where the affect-contingent judgement bias has been produced by objectively measured positive emotions. We trained rats in operant Skinner boxes to press one lever in response to one tone to receive a food reward and to press another lever in response to a different tone to avoid punishment by electric foot shock. After attaining a stable level of discrimination performance, the animals were subjected to either handling or playful, experimenter-administered manual stimulation - tickling. This procedure has been confirmed to induce a positive affective state in rats, and the 50-kHz ultrasonic vocalisations (rat laughter emitted by animals in response to tickling have been postulated to index positive emotions akin to human joy. During the tickling and handling sessions, the numbers of emitted high-frequency 50-kHz calls were scored. Immediately after tickling or handling, the animals were tested for their responses to a tone of intermediate frequency, and the pattern of their responses to this ambiguous cue was taken as an indicator of the animals' optimism. Our findings indicate that tickling induced positive emotions which are directly indexed in rats by laughter, can make animals more optimistic. We demonstrate for the first time a link between the directly measured positive affective state and decision making under uncertainty in an animal model. We also introduce innovative tandem-approach for studying emotional-cognitive interplay in animals, which may be of great value for understanding the emotional

  4. Tubuloglomerular feedback in Dahl rats

    DEFF Research Database (Denmark)

    Karlsen, F M; Leyssac, P P; Holstein-Rathlou, N H

    1998-01-01

    in both Dahl-S and salt-resistant Dahl rats on high- and low-salt diets. TGF was investigated in the closed-loop mode with a videometric technique, in which the response in late proximal flow rate to perturbations in Henle flow rate was measured. All Dahl rats showed a similar compensatory response...

  5. Neutron radiography of osteopetrotic rat

    International Nuclear Information System (INIS)

    Graf, B.; Renard, G.; Le Gall, J.; Laporte, A.

    1983-01-01

    The osteopetrotic disease is characterized by bone and cartilage tissue coexistence in the medullary space of long bones. The authors have studied ''congenital osteopetrosis'' of ''op'' rats. Comparing radiography, neutrography and histology, the evolution of the ''osteopetrotic disease'' and the healing of the ill rats by a single injection of bone marrow from normal animals is shown. (Auth.)

  6. The three-kidney rat

    International Nuclear Information System (INIS)

    Provoost, A.P.; Van Aken, M.

    1984-01-01

    In contrast to the numerous research into the adaption of renal function when nephons are lost, much less attention has been paid to the effects of an extra kidney. Through the availability of inbred rat strains, techniques to transplant rat kidneys, and methods to measure total and individual kidney function repeatedly in the same animal, it became possible to study the renal function in rats with three kidneys. Adult male rats of a highly inbred Wistar strain were used. Nine recipients of a third kidney (3-K) were compared with 5 sham operated control (2-K) rats. The total GFR, as measured by the plasma clearance of Cr-5l EDTA, was taken 1,3,6,9, and 15 weeks after operation. The contribution of each kidney to the total renal function was determined by a Tc-99m DTPA scan performed at weeks 10 and 16. After transplantation the total GFR of 3-K rats was, in general, not different from the value before transplantation or from that of 2-K rats. The lack of increase of the GFR of 3-K rats was not the result of a non-functioning graft

  7. Characterization of cognitive deficits in rats overexpressing human alpha-synuclein in the ventral tegmental area and medial septum using recombinant adeno-associated viral vectors.

    Science.gov (United States)

    Hall, Hélène; Jewett, Michael; Landeck, Natalie; Nilsson, Nathalie; Schagerlöf, Ulrika; Leanza, Giampiero; Kirik, Deniz

    2013-01-01

    Intraneuronal inclusions containing alpha-synuclein (a-syn) constitute one of the pathological hallmarks of Parkinson's disease (PD) and are accompanied by severe neurodegeneration of A9 dopaminergic neurons located in the substantia nigra. Although to a lesser extent, A10 dopaminergic neurons are also affected. Neurodegeneration of other neuronal populations, such as the cholinergic, serotonergic and noradrenergic cell groups, has also been documented in PD patients. Studies in human post-mortem PD brains and in rodent models suggest that deficits in cholinergic and dopaminergic systems may be associated with the cognitive impairment seen in this disease. Here, we investigated the consequences of targeted overexpression of a-syn in the mesocorticolimbic dopaminergic and septohippocampal cholinergic pathways. Rats were injected with recombinant adeno-associated viral vectors encoding for either human wild-type a-syn or green fluorescent protein (GFP) in the ventral tegmental area and the medial septum/vertical limb of the diagonal band of Broca, two regions rich in dopaminergic and cholinergic neurons, respectively. Histopathological analysis showed widespread insoluble a-syn positive inclusions in all major projections areas of the targeted nuclei, including the hippocampus, neocortex, nucleus accumbens and anteromedial striatum. In addition, the rats overexpressing human a-syn displayed an abnormal locomotor response to apomorphine injection and exhibited spatial learning and memory deficits in the Morris water maze task, in the absence of obvious spontaneous locomotor impairment. As losses in dopaminergic and cholinergic immunoreactivity in both the GFP and a-syn expressing animals were mild-to-moderate and did not differ from each other, the behavioral impairments seen in the a-syn overexpressing animals appear to be determined by the long term persisting neuropathology in the surviving neurons rather than by neurodegeneration.

  8. The effect of low frequency stimulation of the pedunculopontine tegmental nucleus on basal ganglia in a rat model of Parkinson's disease.

    Science.gov (United States)

    Park, Eunkyoung; Song, Inho; Jang, Dong Pyo; Kim, In Young

    2014-08-08

    The pedunculopontine nucleus (PPN) has recently been introduced as an alternative target to the subthalamic nucleus (STN) or globus pallidus internus (GPi) for the treatment of advanced Parkinson's disease with severe and medically intractable axial symptoms such as gait and postural impairment. However, it is little known about how electrical stimulation of the PPN affects control of neuronal activities between the PPN and basal ganglia. We examined how low frequency stimulation of the pedunculopontine tegmental nucleus (PPTg) affects control of neuronal activities between the PPN and basal ganglia in 6-OHDA lesioned rats. In order to identify the effect of low frequency stimulation on the PPTg, neuronal activity in both the STN and substantia nigra par reticulata (SNr) were recorded and subjected to quantitative analysis, including analysis of firing rates and firing patterns. In this study, we found that the firing rates of the STN and SNr were suppressed during low frequency stimulation of the PPTg. However, the firing pattern, in contrast to the firing rate, did not exhibit significant changes in either the STN or SNr of 6-OHDA lesioned rats during low frequency stimulation of the PPTg. In addition, we also found that the firing rate of STN and SNr neurons displaying burst and random pattern were decreased by low frequency stimulation of PPTg, while the neurons displaying regular pattern were not affected. These results indicate that low frequency stimulation of the PPTg affects neuronal activity in both the STN and SNr, and may represent electrophysiological efficacy of low frequency PPN stimulation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Quantitative autoradiography of the binding sites for [125I] iodoglyburide, a novel high-affinity ligand for ATP-sensitive potassium channels in rat brain

    International Nuclear Information System (INIS)

    Gehlert, D.R.; Gackenheimer, S.L.; Mais, D.E.; Robertson, D.W.

    1991-01-01

    We have developed a high specific activity ligand for localization of ATP-sensitive potassium channels in the brain. When brain sections were incubated with [ 125 I]iodoglyburide (N-[2-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]ethyl]-5- 125 I-2- methoxybenzamide), the ligand bound to a single site with a KD of 495 pM and a maximum binding site density of 176 fmol/mg of tissue. Glyburide was the most potent inhibitor of specific [ 125 I]iodoglyburide binding to rat forebrain sections whereas iodoglyburide and glipizide were slightly less potent. The binding was also sensitive to ATP which completely inhibited binding at concentrations of 10 mM. Autoradiographic localization of [ 125 I]iodoglyburide binding indicated a broad distribution of the ATP-sensitive potassium channel in the brain. The highest levels of binding were seen in the globus pallidus and ventral pallidum followed by the septohippocampal nucleus, anterior pituitary, the CA2 and CA3 region of the hippocampus, ventral pallidum, the molecular layer of the cerebellum and substantia nigra zona reticulata. The hilus and dorsal subiculum of the hippocampus, molecular layer of the dentate gyrus, cerebral cortex, lateral olfactory tract nucleus, olfactory tubercle and the zona incerta contained relatively high levels of binding. A lower level of binding (approximately 3- to 4-fold) was found throughout the remainder of the brain. These results indicate that the ATP-sensitive potassium channel has a broad presence in the rat brain and that a few select brain regions are enriched in this subtype of neuronal potassium channels

  10. Redox modulation of cellular stress response and lipoxin A4 expression by Hericium Erinaceus in rat brain: relevance to Alzheimer's disease pathogenesis.

    Science.gov (United States)

    Trovato, A; Siracusa, R; Di Paola, R; Scuto, M; Ontario, M L; Bua, Ornella; Di Mauro, Paola; Toscano, M A; Petralia, C C T; Maiolino, L; Serra, A; Cuzzocrea, S; Calabrese, Vittorio

    2016-01-01

    There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses. Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat. Expression of Lipoxin A4 (LXA4) was measured in different brain regions after oral administration of a biomass Hericium preparation, given for 3 month. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, Heme oxygenase -1 and Thioredoxin. In the brain of rats receiving Hericium, maximum induction of LXA4 was observed in cortex, and hippocampus followed by substantia Nigra, striatum and cerebellum. Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is a fundamental cause in neurodegenerative diseases. As prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and Lipoxin A4. Emerging interest is now focussing on molecules capable of activating the vitagene system as novel therapeutic target to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. LXA4 is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. In addition, Hsp system is emerging as key pathway for modulation to prevent neuronal dysfunction, caused by protein misfolding. Conceivably, activation of

  11. Extracellular Zn2+ Influx into Nigral Dopaminergic Neurons Plays a Key Role for Pathogenesis of 6-Hydroxydopamine-Induced Parkinson's Disease in Rats.

    Science.gov (United States)

    Tamano, Haruna; Nishio, Ryusuke; Morioka, Hiroki; Takeda, Atsushi

    2018-04-29

    Parkinson's disease (PD) is a progressive neurological disease characterized by a selective loss of nigrostriatal dopaminergic neurons. The exact cause of the neuronal loss remains unclear. Here, we report a unique mechanism of nigrostriatal dopaminergic neurodegeneration, in which extracellular Zn 2+ influx plays a key role for PD pathogenesis induced with 6-hydroxydopamine (6-OHDA) in rats. 6-OHDA rapidly increased intracellular Zn 2+ only in the substantia nigra pars compacta (SNpc) of brain slices and this increase was blocked in the presence of CaEDTA, an extracellular Zn 2+ chelator, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, indicating that 6-OHDA rapidly increases extracellular Zn 2+ influx via AMPA receptor activation in the SNpc. Extracellular Zn 2+ concentration was decreased under in vivo SNpc perfusion with 6-OHDA and this decrease was blocked by co-perfusion with CNQX, supporting 6-OHDA-induced Zn 2+ influx via AMPA receptor activation in the SNpc. Interestingly, both 6-OHDA-induced loss of nigrostriatal dopaminergic neurons and turning behavior to apomorphine were ameliorated by co-injection of intracellular Zn 2+ chelators, i.e., ZnAF-2DA and N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Co-injection of TPEN into the SNpc blocked 6-OHDA-induced increase in intracellular Zn 2+ but not in intracellular Ca 2+ . These results suggest that the rapid influx of extracellular Zn 2+ into dopaminergic neurons via AMPA receptor activation in the SNpc induces nigrostriatal dopaminergic neurodegeneration, resulting in 6-OHDA-induced PD in rats.

  12. The influence of serotonin depletion on rat behavior in the Vogel test and brain 3H-zolpidem binding.

    Science.gov (United States)

    Nazar, M; Siemiatkowski, M; Bidziński, A; Członkowska, A; Sienkiewicz-Jarosz, H; Płaźnik, A

    1999-01-01

    The influence of p-chlorophenylalanine (p-CPA) and 5,7-dihydroxytryptamine (5,7-DHT)-induced serotonin depletion on rat behavior as well as on zolpidem's the behavioral effects and binding to some brain areas of zolpidem, was examined with the help of Vogel's punished drinking test and autoradiography, respectively. Moreover, changes in the serotonin levels and turnover rate were studied in the forebrain and brainstem of rats pretreated with various ligands at the benzodiazepine (BDZ) receptors (midazolam, bretazenil, abecarnil, zolpidem). These drugs were given at doses shown previously to significantly disinhibit animal behavior suppressed by punishment in the Vogel test (Nazar et al., 1997). It was found that serotonin decrease in the frontal cortex and hippocampus after p-CPA significantly and inversely correlated with rat behavior controlled by fear in the VT. p-CPA produced an anticonflict activity in the absence of effect on spontaneous drinking, pain threshold and motility of animals. All applied benzodiazepine receptor ligands decreased the 5-HT turnover rate in the frontal cortex and hippocampus, whereas in the brainstem only abecarnil and zolpidem diminished 5-hydroxyindoleacetic acid levels. This part of the study replicated earlier data with neurotoxins and indicated that the anxiolytic-like effect of 5-HT depletion in some models of anxiety did not depend on changes in animal appetitive behavior or stimulus control. Moreover, the fact that all nonselective and selective (zolpidem) agonists of the type 1 benzodiazepine receptors seemed to produce the same anticonflict effect and decreasing 5-HT turnover indicates that this subtype of benzodiazepine receptor may be important for the interaction between brain 5-HT and GABA/BDZ systems. Accordingly, it was found that serotonin decrease enhanced the anticonflict effect of zolpidem in the Vogel test and increased 3H-zolpidem binding to the occipital cortex and substantia nigra. Altogether, the present study

  13. Novel AAV-based rat model of forebrain synucleinopathy shows extensive pathologies and progressive loss of cholinergic interneurons.

    Directory of Open Access Journals (Sweden)

    Patrick Aldrin-Kirk

    Full Text Available Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein over-expression, and its link to Parkinson's disease, is well studied, animal models recapitulating the cortical degeneration in dementia with Lewy-bodies (DLB are much less mature. The aim of this study was to develop a first rat model of widespread progressive synucleinopathy throughout the forebrain using adeno-associated viral (AAV vector mediated gene delivery. Through bilateral injection of an AAV6 vector expressing human wild-type α-synuclein into the forebrain of neonatal rats, we were able to achieve widespread, robust α-synuclein expression with preferential expression in the frontal cortex. These animals displayed a progressive emergence of hyper-locomotion and dysregulated response to the dopaminergic agonist apomorphine. The animals receiving the α-synuclein vector displayed significant α-synuclein pathology including intra-cellular inclusion bodies, axonal pathology and elevated levels of phosphorylated α-synuclein, accompanied by significant loss of cortical neurons and a progressive reduction in both cortical and striatal ChAT positive interneurons. Furthermore, we found evidence of α-synuclein sequestered by IBA-1 positive microglia, which was coupled with a distinct change in morphology. In areas of most prominent pathology, the total α-synuclein levels were increased to, on average, two-fold, which is similar to the levels observed in patients with SNCA gene triplication, associated with cortical Lewy body pathology. This study provides a novel rat model of progressive cortical synucleinopathy, showing for the first time that cholinergic interneurons are vulnerable

  14. Do rats have orgasms?

    Science.gov (United States)

    Pfaus, James G.; Scardochio, Tina; Parada, Mayte; Gerson, Christine; Quintana, Gonzalo R.; Coria-Avila, Genaro A.

    2016-01-01

    Background Although humans experience orgasms with a degree of statistical regularity, they remain among the most enigmatic of sexual responses; difficult to define and even more difficult to study empirically. The question of whether animals experience orgasms is hampered by similar lack of definition and the additional necessity of making inferences from behavioral responses. Method Here we define three behavioral criteria, based on dimensions of the subjective experience of human orgasms described by Mah and Binik, to infer orgasm-like responses (OLRs) in other species: 1) physiological criteria that include pelvic floor and anal muscle contractions that stimulate seminal emission and/or ejaculation in the male, or that stimulate uterine and cervical contractions in the female; 2) short-term behavioral changes that reflect immediate awareness of a pleasurable hedonic reward state during copulation; and 3) long-term behavioral changes that depend on the reward state induced by the OLR, including sexual satiety, the strengthening of patterns of sexual arousal and desire in subsequent copulations, and the generation of conditioned place and partner preferences for contextual and partner-related cues associated with the reward state. We then examine whether physiological and behavioral data from observations of male and female rats during copulation, and in sexually-conditioned place- and partner-preference paradigms, are consistent with these criteria. Results Both male and female rats display behavioral patterns consistent with OLRs. Conclusions The ability to infer OLRs in rats offers new possibilities to study the phenomenon in neurobiological and molecular detail, and to provide both comparative and translational perspectives that would be useful for both basic and clinical research. PMID:27799081

  15. Do rats have orgasms?

    Directory of Open Access Journals (Sweden)

    James G. Pfaus

    2016-10-01

    Full Text Available Background: Although humans experience orgasms with a degree of statistical regularity, they remain among the most enigmatic of sexual responses; difficult to define and even more difficult to study empirically. The question of whether animals experience orgasms is hampered by similar lack of definition and the additional necessity of making inferences from behavioral responses. Method: Here we define three behavioral criteria, based on dimensions of the subjective experience of human orgasms described by Mah and Binik, to infer orgasm-like responses (OLRs in other species: 1 physiological criteria that include pelvic floor and anal muscle contractions that stimulate seminal emission and/or ejaculation in the male, or that stimulate uterine and cervical contractions in the female; 2 short-term behavioral changes that reflect immediate awareness of a pleasurable hedonic reward state during copulation; and 3 long-term behavioral changes that depend on the reward state induced by the OLR, including sexual satiety, the strengthening of patterns of sexual arousal and desire in subsequent copulations, and the generation of conditioned place and partner preferences for contextual and partner-related cues associated with the reward state. We then examine whether physiological and behavioral data from observations of male and female rats during copulation, and in sexually-conditioned place- and partner-preference paradigms, are consistent with these criteria. Results: Both male and female rats display behavioral patterns consistent with OLRs. Conclusions: The ability to infer OLRs in rats offers new possibilities to study the phenomenon in neurobiological and molecular detail, and to provide both comparative and translational perspectives that would be useful for both basic and clinical research.

  16. The academic rat race

    DEFF Research Database (Denmark)

    Landes, Xavier; Andersen, Martin Marchman; Nielsen, Morten Ebbe Juul

    2012-01-01

    : an increased pressure to produce articles (in peer-reviewed journals) has created an unbalanced emphasis on the research criterion at the expense of the latter two. More fatally, this pressure has turned academia into a rat race, leading to a deep change in the fundamental structure of academic behaviour......, and entailing a self-defeating and hence counter-productive pattern, where more publications is always better and where it becomes increasingly difficult for researchers to keep up with the new research in their field. The article identifies the pressure to publish as a problem of collective action. It ends up...

  17. The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats.

    Directory of Open Access Journals (Sweden)

    Sebastián eHormigo

    2012-06-01

    Full Text Available The inferior colliculus (IC and the locus coeruleus (LC are two midbrain nuclei that integrate multimodal information and play a major role in novelty detection to elicit an orienting response. Despite the reciprocal connections between these two structures, the projection pattern and target areas of the LC within the subdivisions of the rat IC are still unknown. Here, we used tract-tracing approaches combined with immunohistochemistry, densitometry and confocal microscopy analysis to describe a projection from the LC to the IC. Biotinylated dextran amine (BDA injections into the LC showed that the LC-IC projection is mainly ipsilateral (90% and reaches, to a major extent, the dorsal and lateral part of the IC and the intercollicular commissure. Additionally, some LC fibers extend into the central nucleus of the IC. The neurochemical nature of this projection is noradrenergic, given that tyrosine hydroxylase (TH and dopamine beta hydroxylase (DBH colocalize with the BDA-labeled fibers from the LC. To determine the total field of the LC innervations in the IC, we destroyed the LC neurons and fibers using a highly selective neurotoxin, DSP-4, and then studied the distribution and density of TH- and DBH-immunolabeled axons in the IC. In the DSP-4 treated animals, the number of axonal fibers immunolabeled for TH and DBH were deeply decreased throughout the entire rostrocaudal extent of the IC and its subdivisions compared to controls. Our densitometry results showed that the IC receives up to 97% of its noradrenergic innervations from the LC neurons and only 3% from non-coeruleus neurons. Our results also indicate that TH immunoreactivity in the IC was less impaired than the immunoreactivity for DBH after DSP-4 administration. This is consistent with the existence of an important dopaminergic projection from the substantia nigra to the IC. In conclusion, our study demonstrates and quantifies the noradrenergic projection from the LC to the IC and its

  18. The anorexic agents, sibutramine and fenfluramine, depress GABAB-induced inhibitory postsynaptic potentials in rat mesencephalic dopaminergic cells

    Science.gov (United States)

    Ledonne, Ada; Sebastianelli, Luca; Federici, Mauro; Bernardi, Giorgio; Mercuri, Nicola Biagio

    2009-01-01

    Background and purpose Nutrition is the result of a complex interaction among environmental, homeostatic and reward-related processes. Accumulating evidence supports key roles for the dopaminergic neurons of the ventral midbrain in regulating feeding behaviour. For this reason, in the present study, we have investigated the electrophysiological effects of two centrally acting anorexic agents, fenfluramine and sibutramine, on these cells. Experimental approach Rat midbrain slices were used to make intracellular recordings from dopaminergic neurons of the substantia nigra and the ventral tegmental area. Gamma-aminobutyric acid (GABA)-mediated synaptic transmission was assessed from the inhibitory postsynaptic potentials (IPSPs) mediated by GABAA and GABAB receptors. Key results Fenfluramine and sibutramine reduced, concentration-dependently, the GABAB IPSPs, without affecting the GABAA-mediated potentials. This effect is presynaptic, as postsynaptic membrane responses induced by application of a GABAB receptor agonist, baclofen, were not affected by the two drugs. Furthermore, the selective 5-hydroxytriptamine 1B (5-HT1B) receptor antagonist, SB216641, blocked the reduction of GABAB IPSPs caused by fenfluramine and sibutramine, indicating that the receptor mediating this effect is 5-HT1B. Conclusions and implications Two anorexic agents, fenfluramine and sibutramine, induced the activation of 5-HT1B receptors located on presynaptic GABAergic terminals, thus reducing the release of GABA. This action can alter the strength of synaptic afferents that modify the activity of dopaminergic neurons, inducing neuronal excitation. Our results reveal an additional mechanism of action for fenfluramine and sibutramine that might contribute to reducing food intake, by influencing the pleasurable and motor aspects of feeding behaviour. PMID:19298257

  19. The Rat Race

    CERN Multimedia

    Stephen Haywood

    Dear Muriel, Being an animal, you are probably more familiar with rats than most of us. Yet it seems to me that our Community (not just ATLAS) is stuck in a huge "rat race". I am somewhat mystified as to how we have got ourselves into this and I wonder whether you or your readers could explain this - I give my own observations below. In HEP and ATLAS specifically, we are all working long hours and we are all becoming exhausted. There are people at Point 1 who are working day and night, every day of the week; there are people writing software who send emails round the clock, including weekends. It is one thing to have bursts of activity which require us to put in some longer hours, but in ATLAS, the bursts last months or years. I have been on ATLAS 14 years and it has felt like one endless rush. Why do we do this? We are all highly motivated, we love our work and want to succeed individually and collectively. We are parts of various teams, and we do not want to let the side down. We worked hard at school an...

  20. Selective activation of primary afferent fibers evaluated by sine-wave electrical stimulation

    Directory of Open Access Journals (Sweden)

    Katafuchi Toshihiko

    2005-03-01

    Full Text Available Abstract Transcutaneous sine-wave stimuli at frequencies of 2000, 250 and 5 Hz (Neurometer are thought to selectively activate Aβ, Aδ and C afferent fibers, respectively. However, there are few reports to test the selectivity of these stimuli at the cellular level. In the present study, we analyzed action potentials (APs generated by sine-wave stimuli applied to the dorsal root in acutely isolated rat dorsal root ganglion (DRG preparations using intracellular recordings. We also measured excitatory synaptic responses evoked by transcutaneous stimuli in substantia gelatinosa (SG neurons of the spinal dorsal horn, which receive inputs predominantly from C and Aδ fibers, using in vivo patch-clamp recordings. In behavioral studies, escape or vocalization behavior of rats was observed with both 250 and 5 Hz stimuli at intensity of ~0.8 mA (T5/ T250, whereas with 2000 Hz stimulation, much higher intensity (2.14 mA, T2000 was required. In DRG neurons, APs were generated at T5/T250 by 2000 Hz stimulation in Aβ, by 250 Hz stimulation both in Aβ and Aδ, and by 5 Hz stimulation in all three classes of DRG neurons. However, the AP frequencies elicited in Aβ and Aδ by 5 Hz stimulation were much less than those reported previously in physiological condition. With in vivo experiments large amplitude of EPSCs in SG neurons were elicited by 250 and 5 Hz stimuli at T5/ T250. These results suggest that 2000 Hz stimulation excites selectively Aβ fibers and 5 Hz stimulation activates noxious transmission mediated mainly through C fibers. Although 250 Hz stimulation activates both Aδ and Aβ fibers, tactile sensation would not be perceived when painful sensation is produced at the same time. Therefore, 250 Hz was effective stimulus frequency for activation of Aδ fibers initiating noxious sensation. Thus, the transcutaneous sine-wave stimulation can be applied to evaluate functional changes of sensory transmission by comparing thresholds with the three

  1. Serotonin metabolism in rat brain

    International Nuclear Information System (INIS)

    Schutte, H.H.

    1976-01-01

    The metabolism of serotonin in rat brain was studied by measuring specific activities of tryptophan in plasma and of serotonin, 5-hydroxyindole acetic acid and tryptophan in the brain after intravenous injection of tritiated tryptophan. For a detailed analysis of the specific activities, a computer simulation technique was used. It was found that only a minor part of serotonin in rat brain is synthesized from tryptophan rapidly transported from the blood. It is suggested that the brain tryptophan originates from brain proteins. It was also found that the serotonin in rat brain is divided into more than one metabolic compartment

  2. Beta-endorphin in genetically hypoprolactinemic rat: IPL nude rat

    International Nuclear Information System (INIS)

    Cohen, H.; Sabbagh, I.; Abou-Samra, A.B.; Bertrand, J.

    1986-01-01

    Beta-endorphin has been reported to regulate not only stress- and suckling-induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, the authors measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation: IPL nude rat. Beta-endorphin was measured using a specific anti-h-β endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extracts from male rats showed greater immunoactivity eluting as I 125 h-beta-endorphin than in normal rat; this was not the case for the female rat. These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin. 40 references, 2 figures, 4 tables

  3. Beta-endorphin in genetically hypoprolactinemic rat: IPL nude rat

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, H.; Sabbagh, I.; Abou-Samra, A.B.; Bertrand, J.

    1986-01-20

    Beta-endorphin has been reported to regulate not only stress- and suckling-induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, the authors measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation: IPL nude rat. Beta-endorphin was measured using a specific anti-h-..beta.. endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extracts from male rats showed greater immunoactivity eluting as I/sup 125/ h-beta-endorphin than in normal rat; this was not the case for the female rat. These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin. 40 references, 2 figures, 4 tables.

  4. Intramitochondrial autonomy in rat tissues

    International Nuclear Information System (INIS)

    Subramanian, M.; Rajwade, M.S.; Satav, J.G.; Katyare, S.S.; Fatterpaker, P.; Sreenivasan, A.

    1974-01-01

    The biogenesis of mitochondria in rat liver and their protein turnover has been investigated using 1- 14 C leucine. The results indicate that intramitochondrial autonomy exists both with respect to their genesis and turnover. (M.G.B.)

  5. Autoshaping in micrencephalic rats

    International Nuclear Information System (INIS)

    Goldstein, L.H.; Oakley, D.A.

    1989-01-01

    An autoshaping procedure in which the illumination of a lever was predictive of food reinforcement was used to compare learning in rats with micrencephaly induced by irradiation on the 16th day of gestation and in sham-irradiated controls. Both groups showed equivalent levels of lever-directed activity, and the micrencephalic animals differentiated as well as the control animals between the predictive lever and a nonpredictive lever. The micrencephalic animals were able to redistribute their lever-directed activity when the significance of the levers was reversed and did so more readily than the control animals. Results support the claim that association learning survives either traumatic or developmental neocortical damage and have implications for remedial procedures following both head injury and developmental cerebral pathology in humans

  6. Autoshaping in micrencephalic rats.

    Science.gov (United States)

    Goldstein, L H; Oakley, D A

    1989-06-01

    An autoshaping procedure in which the illumination of a lever was predictive of food reinforcement was used to compare learning in rats with micrencephaly induced by irradiation on the 16th day of gestation and in sham-irradiated controls. Both groups showed equivalent levels of lever-directed activity, and the micrencephalic animals differentiated as well as the control animals between the predictive lever and a nonpredictive lever. The micrencephalic animals were able to redistribute their lever-directed activity when the significance of the levers was reversed and did so more readily than the control animals. Results support the claim that association learning survives either traumatic or developmental neocortical damage and have implications for remedial procedures following both head injury and developmental cerebral pathology in humans.

  7. Biokinetics of radiotellurium in rats

    International Nuclear Information System (INIS)

    Nishimura, Y.; Sahoo, S.K.; Kim, S.; Homma-Takeda, S.; Watanabe, Y.; Inaba, J.

    2003-01-01

    Radiotellurium is present in the environment primarily due to its release during nuclear reactor accidents. Little is known of tellurium metabolism in juveniles, although the element is relatively abundant and has a number of industrial uses. A biokinetic study of radiotellurium in rats was done using gamma-ray counting. Wistar strain rats were used to determine the uptake of H 2 123 Te m O 3 by the whole-body retention of juvenile rats and the conceptus in relation to its gestational stages, by measurements in the placenta, fetal membranes, fetal fluid, and fetus. The whole-body retention of 123 Te m in juvenile rats was higher than that of adult rats. The relative concentration in the placenta and fetal membranes was higher than in the fetus. No activity was observed in the fetal fluid. These results indicate that the placenta and fetal membranes play significant roles as barriers to the transfer of 123 Te m into the fetus. The ratio, relative concentration in fetus/relative concentration in mother (C F /C M ), was calculated. The C F /C M ratio was dependent on the stage of gestation and ranged from 0.2 to 0.5. A little 123 Te m was transferred to the suckling rats through the mother's milk when the isotope was administered intravenously to the mother. (author)

  8. Tryptophan depletion affects compulsive behaviour in rats

    DEFF Research Database (Denmark)

    Merchán, A; Navarro, S V; Klein, A B

    2017-01-01

    investigated whether 5-HT manipulation, through a tryptophan (TRP) depletion by diet in Wistar and Lister Hooded rats, modulates compulsive drinking in schedule-induced polydipsia (SIP) and locomotor activity in the open-field test. The levels of dopamine, noradrenaline, serotonin and its metabolite were......-depleted HD Wistar rats, while the LD Wistar and the Lister Hooded rats did not exhibit differences in SIP. In contrast, the TRP-depleted Lister Hooded rats increased locomotor activity compared to the non-depleted rats, while no differences were found in the Wistar rats. Serotonin 2A receptor binding...

  9. Population Structure of Rat-Derived Pneumocystis carinii in Danish Wild Rats

    DEFF Research Database (Denmark)

    Palmer, Robert J.; Settnes, Osvald P.; Lodal, Jens

    2000-01-01

    The rat model of Pneumocystis carinii pneumonia is frequently used to study human P. carinii infection, but there are many differences between the rat and human infections. We studied naturally acquired P. carinii in wild rats to examine the relevance of the rat model for human infection. P. cari...

  10. Lead-Induced Atypical Parkinsonism in Rats: Behavioral, Electrophysiological, and Neurochemical Evidence for a Role of Noradrenaline Depletion

    Directory of Open Access Journals (Sweden)

    Mariam Sabbar

    2018-03-01

    Full Text Available Background: Lead neurotoxicity is a major health problem known as a risk factor for neurodegenerative diseases, including the manifestation of parkinsonism-like disorder. While lead is known to preferentially accumulate in basal ganglia, the mechanisms underlying behavioral disorders remain unknown. Here, we investigated the neurophysiological and biochemical correlates of motor deficits induced by sub-chronic injections of lead.Methods: Sprague Dawely rats were exposed to sub-chronic injections of lead (10 mg/kg, i.p. or to a single i.p. injection of 50 mg/kg N-(2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, a drug known to induce selective depletion of noradrenaline. Rats were submitted to a battery of behavioral tests, including the open field for locomotor activity and rotarod for motor coordination. Electrophysiological recordings were carried out in three major basal ganglia nuclei, the subthalamic nucleus (STN, globus pallidus (GP, and substantia nigra pars reticulata (SNr. At the end of experiments, post-mortem tissue level of the three monoamines (dopamine, noradrenaline, and serotonin and their metabolites has been determined using HPLC.Results: Lead intoxication significantly impaired exploratory and locomotor activity as well as motor coordination. It resulted in a significant reduction in the level of noradrenaline in the cortex and dopamine and its metabolites, DOPAC, and HVA, in the striatum. The tissue level of serotonin and its metabolite 5-HIAA was not affected in the two structures. Similarly, DSP-4, which induced a selective depletion of noradrenaline, significantly decreased exploratory, and locomotor activity as well as motor coordination. L-DOPA treatment did not improve motor deficits induced by lead and DSP-4 in the two animal groups. Electrophysiological recordings showed that both lead and DSP-4 did not change the firing rate but resulted in a switch from the regular normal firing to irregular and

  11. DOPA, norepinephrine, and dopamine in rat tissues

    DEFF Research Database (Denmark)

    Eldrup, E; Richter, Erik; Christensen, N J

    1989-01-01

    We studied the effect of unilateral sympathectomy on rat quadriceps and gastrocnemius muscle concentrations of endogenous dihydroxyphenylalanine (DOPA), dopamine (DA), and norepinephrine (NE) and assessed the relationships between these catecholamines in several rat tissues. Catecholamines were...

  12. False Context Fear Memory in Rats

    Science.gov (United States)

    Bae, Sarah; Holmes, Nathan M.; Westbrook, R. Frederick

    2015-01-01

    Four experiments used rats to study false context fear memories. In Experiment 1, rats were pre-exposed to a distinctive chamber (context A) or to a control environment (context C), shocked after a delay in a second chamber (context B) and tested either in B or A. Rats pre-exposed to A froze just as much as control rats in B but more than control…

  13. EFFECT OF ETHANOL ON HEPATOBILIARY TRANSPORT OF CATIONIC DRUGS - A STUDY IN THE ISOLATED-PERFUSED RAT-LIVER, RAT HEPATOCYTES AND RAT MITOCHONDRIA

    NARCIS (Netherlands)

    STEEN, H; MEIJER, DKF; Merema, M.T.

    The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation

  14. The serotonin transporter knockout rat : A review

    NARCIS (Netherlands)

    Olivier, Jocelien; Cools, Alexander; Ellenbroek, Bart A.; Cuppen, E.; Homberg, Judith; Kalueff, Allan V.; LaPorte, Justin L.

    2010-01-01

    This chapter dicusses the most recent data on the serotonin transporter knock-out rat, a unique rat model that has been generated by target-selected N-ethyl-N-nitrosourea (ENU) driven mutagenesis. The knock-out rat is the result of a premature stopcodon in the serotonin transporter gene, and the

  15. Tuberculosis Detection by Giant African Pouched Rats

    Science.gov (United States)

    Poling, Alan; Weetjens, Bart; Cox, Christophe; Beyene, Negussie; Durgin, Amy; Mahoney, Amanda

    2011-01-01

    In recent years, operant discrimination training procedures have been used to teach giant African pouched rats to detect tuberculosis (TB) in human sputum samples. This article summarizes how the rats are trained and used operationally, as well as their performance in studies published to date. Available data suggest that pouched rats, which can…

  16. Teratology studies in the rat.

    Science.gov (United States)

    Leroy, Mariline; Allais, Linda

    2013-01-01

    The rat is the rodent species of choice for the regulatory safety testing of xenobiotics, such as medicinal products, food additives, and other chemicals. Many decades of experience and extensive data have accumulated for both general and developmental toxicology investigations in this species. The high fertility and large litter size of the rat are advantages for teratogenicity testing. The study designs are well defined in the regulatory guidelines and are relatively standardized between testing laboratories across the world. Teratology studies address maternal- and embryo-toxicity following exposure during the period of organogenesis. This chapter describes the design and conduct of a teratology study in the rat in compliance with the regulatory guidelines. The procedures for the handling and housing of the pregnant animals, the caesarean examinations and the sampling of fetuses for morphological examinations are described. The utility and design of preliminary studies and the inclusion of satellite animals in the main study for toxicokinetic sampling are discussed.

  17. [Food-procuring stereotype movements is accompanied by changes of c-Fos gene expression in the amygdala and modulation of heart rate in rats].

    Science.gov (United States)

    Dovgan', O V; Vlasenko, O V; Buzyka, T V; Maĭs'kyĭ, V O; Piliavs'kyĭ, O I; Maznychenko, A V

    2012-01-01

    The distribution of Fos-immunoreactive (Fos-ir) and NADPH Diaphorase reactive (NADPH-dr-) neurons in the different subnuclei of amygdala and insular cortex (on the level -2,12 to -3,14 mm from bregma), and the associated changes of heart rate (HR) in intact, food-deprivated and executed food-procuring movements of rats were studied. In comparison with other groups of animals, the mean number of the Fos-ir neurons in the central nucleus of amygdala (Ce) and the insular cortex (GI/DI) at all studied levels was significantly greater in the executed food-procuring movements in rats. The main focus of localization of the Fos-ir neurons was found in lateral part of the Ce (58.5 +/- 1.9 units in 40-microm-thick section) at the level -2.56 mm. The mean number of Fos-ir neurons was significantly greater also in the lateral and capsular parts of the Ce. The mean number of Fos-ir neurons in the GI/DI was 165.5 +/- 3.2 cells in section. The number and density of NADPH-d reactive neurons was not significantly different in the brain structures of all animal groups studied. The double stained neurons (Fos-ir + NADPH-dr) were registered in medial, basolateral, anterior cortical amygdaloid nuclei and substantia innominata (SI) in rats after realization food-procuring movements. It was found that realization of food-procuring movements by the forelimb during repeated sessions was accompanied with the gradual decline of mean values of the HR (from 5% to 12% of control level) with subsequent renewal of them to the initial values (tonic component). The analysis of dynamics of the HR changes during realization of separate purposeful motion has shown the transient period of the HR suppression (500 ms), which coincided with the terminal phase of grasping of food pellet (phasic component). We suggest that the revealed focuses of localization of Fos-ir neurons in the lateral and medial subregions of amigdaloid Ce and also GI/DI, and SI testified that these structures of brain are involved

  18. Morphological and metabolic changes in the nigro-striatal pathway of synthetic proteasome inhibitor (PSI-treated rats: a MRI and MRS study.

    Directory of Open Access Journals (Sweden)

    Stefano Delli Pizzi

    Full Text Available Systemic administration of a Synthetic Proteasome Inhibitor (PSI in rats has been described as able to provide a model of Parkinson's disease (PD, characterized by behavioral and biochemical modifications, including loss of dopaminergic neurons in the substantia nigra (SN, as assessed by post-mortem studies. With the present study we aimed to assess in-vivo by Magnetic Resonance (MR possible morphological and metabolic changes in the nigro-striatal pathway of PSI-treated rats. 10 animals were subcutaneously injected with PSI 6.0 mg/kg dissolved in DMSO 100%. Injections were made thrice weekly over the course of two weeks. 5 more animals injected with DMSO 100% with the same protocol served as controls. The animals underwent MR sessions before and at four weeks after the end of treatment with either PSI or vehicle. MR Imaging was performed to measure SN volume and Proton MR Spectroscopy ((1H-MRS was performed to measure metabolites changes at the striatum. Animals were also assessed for motor function at baseline and at 4 and 6 weeks after treatment. Dopamine and dopamine metabolite levels were measured in the striata at 6 weeks after treatment. PSI-treated animals showed volumetric reduction of the SN (p<0.02 at 4 weeks after treatment as compared to baseline. Immunofluorescence analysis confirmed MRI changes in SN showing a reduction of tyrosine hydroxylase expression as compared to neuron-specific enolase expression. A reduction of N-acetyl-aspartate/total creatine ratio (p = 0.05 and an increase of glutamate-glutamine-γ amminobutirrate/total creatine were found at spectroscopy (p = 0.03. At 6 weeks after treatment, PSI-treated rats also showed motor dysfunction compared to baseline (p = 0.02, accompanied by dopamine level reduction in the striatum (p = 0.02. Treatment with PSI produced morphological and metabolic modifications of the nigro-striatal pathway, accompanied by motor dysfunction. MR demonstrated to be a powerful mean to assess in

  19. Distribution of angiotensin converting enzyme in sheep hypothalamus and medulla oblongata visualized by in vitro autoradiography

    International Nuclear Information System (INIS)

    Chai, S.Y.; McKinley, M.J.; Mendelsohn, F.A.

    1987-01-01

    In vitro autoradiographic mapping of angiotensin converting enzyme (ACE) in sheep brain using the specific ACE inhibitor, 125 I-351A, revealed very high densities of binding in large blood vessels and choroid plexus. In the a very high density of labelling occurred in the organum vasculosum of the lamina terminalis and median eminence and a high density in the subfornical organ and moderate density in supraoptic, suprachiasmatic, arcuate and paraventricular nuclei. All fiber tracts were unlabelled. In the medulla oblongata, a very high density of binding was detected in the area postrema and a high density in the nucleus of the solitary tract and dorsal motor nucleus of the vagus; a moderate density was found in the substantia gelatinosa of the spinal tract and the inferior olivary nucleus

  20. Voluntary Sleep Loss in Rats

    Science.gov (United States)

    Oonk, Marcella; Krueger, James M.; Davis, Christopher J.

    2016-01-01

    Study Objectives: Animal sleep deprivation (SDEP), in contrast to human SDEP, is involuntary and involves repeated exposure to aversive stimuli including the inability of the animal to control the waking stimulus. Therefore, we explored intracranial self-stimulation (ICSS), an operant behavior, as a method for voluntary SDEP in rodents. Methods: Male Sprague-Dawley rats were implanted with electroencephalography/electromyography (EEG/EMG) recording electrodes and a unilateral bipolar electrode into the lateral hypothalamus. Rats were allowed to self-stimulate, or underwent gentle handling-induced SDEP (GH-SDEP), during the first 6 h of the light phase, after which they were allowed to sleep. Other rats performed the 6 h ICSS and 1 w later were subjected to 6 h of noncontingent stimulation (NCS). During NCS the individual stimulation patterns recorded during ICSS were replayed. Results: After GH-SDEP, ICSS, or NCS, time in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep increased. Further, in the 24 h after SDEP, rats recovered all of the REM sleep lost during SDEP, but only 75% to 80% of the NREM sleep lost, regardless of the SDEP method. The magnitude of EEG slow wave responses occurring during NREM sleep also increased after SDEP treatments. However, NREM sleep EEG slow wave activity (SWA) responses were attenuated following ICSS, compared to GH-SDEP and NCS. Conclusions: We conclude that ICSS and NCS can be used to sleep deprive rats. Changes in rebound NREM sleep EEG SWA occurring after ICSS, NCS, and GH-SDEP suggest that nonspecific effects of the SDEP procedure differentially affect recovery sleep phenotypes. Citation: Oonk M, Krueger JM, Davis CJ. Voluntary sleep loss in rats. SLEEP 2016;39(7):1467–1479. PMID:27166236

  1. Rat bite fever without fever.

    Science.gov (United States)

    Stehle, P; Dubuis, O; So, A; Dudler, J

    2003-09-01

    Rat bite fever is a rarely reported acute febrile bacterial illness caused by Streptobacillus moniliformis or Spirillum minus following a rat bite. It is classically characterised by abrupt onset of fever with rigors, myalgias, headache, and the appearance of a generalised maculopapular petechial skin rash. Polyarthritis complicates the course of the disease in up to 50% of infected patients, and numerous hurdles can make the diagnosis particularly difficult in the absence of fever or rash, as in the present case. A high degree of awareness is necessary to make the correct diagnosis in such cases. Diagnosis has important prognostic implications as the disease is potentially lethal, but easily treatable.

  2. Differential ontogenetic patterns of levocabastine-sensitive neurotensin NT2 receptors and of NT1 receptors in the rat brain revealed by in situ hybridization.

    Science.gov (United States)

    Lépée-Lorgeoux, I; Betancur, C; Rostène, W; Pélaprat, D

    1999-03-12

    The postnatal ontogeny of the levocabastine-sensitive neurotensin receptor (NT2) mRNA was studied by in situ hybridization in the rat brain and compared with the distribution of the levocabastine-insensitive NT1 receptor. NT2 receptor mRNA was absent at birth from all brain structures except the ependymal cell layer lining the ventricles. The development of NT2 receptor mRNA followed three ontogenetic patterns. The first pattern, involving the majority of the cerebral gray matter, was characterized by a continuous increase from postnatal day 5 (P5) to P30. The second one, involving regions rich in myelinated fibers such as the corpus callosum and lacunosum moleculare layer of the hippocampus, exhibited a pronounced increase between P5 and P10, peaked at P15 and was followed by a plateau or a slight decrease. The third pattern was observed in the ependymal cell layer lining the olfactory and lateral ventricles, where the high labeling already present at birth continued to increase during development. These different developmental patterns could reflect the variety of cells expressing NT2 receptor mRNA, including neurons, protoplasmic astrocytes in gray matter, fibrous astrocytes present in myelinated fibers tracts, and ependymal cells. In contrast, NT1 receptor mRNA, which seems to be associated only with neurons, was highly and transiently expressed during the perinatal period in the cerebral cortex, hippocampus and striatal neuroepithelium. Other regions, notably the ventral tegmental area and substantia nigra compacta, exhibited a gradual increase in NT1 receptor signal, reaching adult levels by P21. Both the differential localization and ontogenetic profiles of NT1 and NT2 receptor mRNAs suggest different involvement of these two receptors in brain functions and development. Copyright 1999 Elsevier Science B.V.

  3. Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible structure-specific plasticity process in 6-OHDA lesioned rats.

    Directory of Open Access Journals (Sweden)

    Gabriela P Chaves-Kirsten

    Full Text Available The endocannabinoid system has been implicated in several neurobiological processes, including neurodegeneration, neuroprotection and neuronal plasticity. The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in Parkinson's Disease (PD. Some studies show variation of CB1 expression in basal ganglia in different animal models of PD, however the results are quite controversial, due to the differences in the procedures employed to induce the parkinsonism and the periods analyzed after the lesion. The present study evaluated the CB1 expression in four basal ganglia structures, namely striatum, external globus pallidus (EGP, internal globus pallidus (IGP and substantia nigra pars reticulata (SNpr of rats 1, 5, 10, 20, and 60 days after unilateral intrastriatal 6-hydroxydopamine injections, that causes retrograde dopaminergic degeneration. We also investigated tyrosine hydroxylase (TH, parvalbumin, calbindin and glutamic acid decarboxylase (GAD expression to verify the status of dopaminergic and GABAergic systems. We observed a structure-specific modulation of CB1 expression at different periods after lesions. In general, there were no changes in the striatum, decreased CB1 in IGP and SNpr and increased CB1 in EGP, but this increase was not sustained over time. No changes in GAD and parvalbumin expression were observed in basal ganglia, whereas TH levels were decreased and the calbindin increased in striatum in short periods after lesion. We believe that the structure-specific variation of CB1 in basal ganglia in the 6-hydroxydopamine PD model could be related to a compensatory process involving the GABAergic transmission, which is impaired due to the lack of dopamine. Our data, therefore, suggest that the changes of CB1 and calbindin expression may represent a plasticity process in this PD model.

  4. Neurokinin B-producing projection neurons in the lateral stripe of the striatum and cell clusters of the accumbens nucleus in the rat.

    Science.gov (United States)

    Zhou, Ligang; Furuta, Takahiro; Kaneko, Takeshi

    2004-12-06

    Neurons producing preprotachykinin B (PPTB), the precursor of neurokinin B, constitute 5% of neurons in the dorsal striatum and project to the substantia innominata (SI) selectively. In the ventral striatum, PPTB-producing neurons are collected mainly in the lateral stripe of the striatum (LSS) and cell clusters of the accumbens nucleus (Acb). In the present study, we first examined the distribution of PPTB-immunoreactive neurons in rat ventral striatum and found that a large part of the PPTB-immunoreactive cell clusters was continuous to the LSS, but a smaller part was not. Thus, we divided the PPTB-immunoreactive cell clusters into the LSS-associated and non-LSS-associated ones. We next investigated the projection targets of the PPTB-producing ventral striatal neurons by combining immunofluorescence labeling and retrograde tracing. After injection of Fluoro-Gold into the basal component of the SI (SIb) and medial part of the interstitial nucleus of posterior limb of the anterior commissure, many PPTB-immunoreactive neurons were retrogradely labeled in the LSS-associated cell clusters and LSS, respectively. When the injection site included the ventral part of the sublenticular component of the SI(SIsl), retrogradely labeled neurons showed PPTB-immunoreactivity frequently in non-LSS-associated cell clusters. Furthermore, these PPTB-immunoreactive projections were confirmed by the double-fluorescence method after anterograde tracer injection into the ventral striatum containing the cell clusters. Since the dorsalmost part of the SIsl is known to receive strong inputs from PPTB-producing dorsal striatal neurons, the present results indicate that PPTB-producing ventral striatal neurons project to basal forebrain target regions in parallel with dorsal striatal neurons without significant convergence. 2004 Wiley-Liss, Inc.

  5. Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin

    International Nuclear Information System (INIS)

    Clarke, P.B.; Schwartz, R.D.; Paul, S.M.; Pert, C.B.; Pert, A.

    1985-01-01

    Three radioligands have been commonly used to label putative nicotinic cholinoceptors in the mammalian central nervous system: the agonists [ 3 H]nicotine and [ 3 H]acetylcholine ([ 3 H]ACh--in the presence of atropine to block muscarinic receptors), and the snake venom extract, [ 125 I]-alpha-bungarotoxin([ 125 I]BTX), which acts as a nicotinic antagonist at the neuromuscular junction. Binding studies employing brain homogenates indicate that the regional distributions of both [ 3 H]nicotine and [ 3 H]ACh differ from that of [ 125 I]BTX. The possible relationship between brain sites bound by [ 3 H]nicotine and [ 3 H]ACh has not been examined directly. The authors have used the technique of autoradiography to produce detailed maps of [ 3 H]nicotine, [ 3 H]ACh, and [ 125 I]BTX labeling; near-adjacent tissue sections were compared at many levels of the rat brain. The maps of high affinity agonist labeling are strikingly concordant, with highest densities in the interpeduncular nucleus, most thalamic nuclei, superior colliculus, medial habenula, presubiculum, cerebral cortex (layers I and III/IV), and the substantia nigra pars compacta/ventral tegmental area. The pattern of [ 125 I]BTX binding is strikingly different, the only notable overlap with agonist binding being the cerebral cortex (layer I) and superior colliculus. [ 125 I]BTX binding is also dense in the inferior colliculus, cerebral cortex (layer VI), hypothalamus, and hippocampus, but is virtually absent in thalamus. Various lines of evidence suggest that the high affinity agonist-binding sites in brain correspond to nicotinic cholinergic receptors similar to those found at autonomic ganglia; BTX-binding sites may also serve as receptors for nicotine and are possibly related to neuromuscular nicotinic cholinoceptors

  6. Pre-α-pro-GDNF and Pre-β-pro-GDNF Isoforms Are Neuroprotective in the 6-hydroxydopamine Rat Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Anna-Maija Penttinen

    2018-06-01

    Full Text Available Glial cell line-derived neurotrophic factor (GDNF is one of the most studied neurotrophic factors. GDNF has two splice isoforms, full-length pre-α-pro-GDNF (α-GDNF and pre-β-pro-GDNF (β-GDNF, which has a 26 amino acid deletion in the pro-region. Thus far, studies have focused solely on the α-GDNF isoform, and nothing is known about the in vivo effects of the shorter β-GDNF variant. Here we compare for the first time the effects of overexpressed α-GDNF and β-GDNF in non-lesioned rat striatum and the partial 6-hydroxydopamine lesion model of Parkinson's disease. GDNF isoforms were overexpressed with their native pre-pro-sequences in the striatum using an adeno-associated virus (AAV vector, and the effects on motor performance and dopaminergic phenotype of the nigrostriatal pathway were assessed. In the non-lesioned striatum, both isoforms increased the density of dopamine transporter-positive fibers at 3 weeks after viral vector delivery. Although both isoforms increased the activity of the animals in cylinder assay, only α-GDNF enhanced the use of contralateral paw. Four weeks later, the striatal tyrosine hydroxylase (TH-immunoreactivity was decreased in both α-GDNF and β-GDNF treated animals. In the neuroprotection assay, both GDNF splice isoforms increased the number of TH-immunoreactive cells in the substantia nigra but did not promote behavioral recovery based on amphetamine-induced rotation or cylinder assays. Thus, the shorter GDNF isoform, β-GDNF, and the full-length α-isoform have comparable neuroprotective efficacy on dopamine neurons of the nigrostriatal circuitry.

  7. Neuroprotective Effects of a Standardized Flavonoid Extract from Safflower against a Rotenone-Induced Rat Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Nuramatjan Ablat

    2016-08-01

    Full Text Available Parkinson’s disease (PD is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc. Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. Safflower (Carthamus tinctorius. L. has long been used to treat cerebrovascular diseases in China. This plant contains flavonoids, which have been reported to be effective in models of neurodegenerative disease. We previously reported that kaempferol derivatives from safflower could bind DJ-1, a protein associated with PD, and that a flavonoid extract from safflower exhibited neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE was isolated from safflower and found to primarily contain flavonoids. The aim of the current study was to confirm the neuroprotective effects of SAFE in rotenone-induced Parkinson rats. The results showed that SAFE treatment increased body weight and improved rearing behavior and grip strength. SAFE (35 or 70 mg/kg/day treatment reversed the decreased protein expression of tyrosine hydroxylase, dopamine transporter and DJ-1 and increased the levels of dopamine and its metabolite. In contrast, acetylcholine levels were decreased. SAFE treatment also led to partial inhibition of PD-associated changes in extracellular space diffusion parameters. These changes were detected using a magnetic resonance imaging (MRI tracer-based method, which provides novel information regarding neuronal loss and astrocyte activation. Thus, our results indicate that SAFE represents a potential therapeutic herbal treatment for PD.

  8. Treatment of diabetic rats with encapsulated islets.

    Science.gov (United States)

    Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

    2008-12-01

    Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We encapsulated 1000 rat islets and implanted them subcutaneously (SQ) into diabetic biobreeding (BB) rats and STZ-induced diabetic rats, defined as two or more consecutive days of blood glucose>350 mg/dl. Rats were monitored for weight and blood glucose. Untreated BB rats rapidly lost weight and were euthanized at >20% weight loss that occurred between 4 and 10 days from implantation. For period of 30-40 days following islet implantation weights of treated rats remained steady or increased. Rapid weight loss occurred after surgical removal of devices that contained insulin positive islets. STZ-treated rats that received encapsulated islets showed steady weight gain for up to 130 days, whereas untreated control rats showed steady weight loss that achieved >20% at around 55 days. Although islet implants did not normalize blood glucose, treated rats were apparently healthy and groomed normally. Autologous or allogeneic islets were equally effective in providing treatment. TheraCyte devices can sustain islets, protect allogeneic cells from immune attack and provide treatment for diabetic-mediated weight loss in both BB rats and STZ-induced diabetic rats.

  9. Induced Chronic Prostatitis in Rats

    African Journals Online (AJOL)

    Similarly, compared with reference group (176.1 ± 12.1 pg/ml), IL-1β level of prostate tissues of high-dose PCS ..... Fig 1: Effect of PCS extract on the histomorphology of prostate tissues in rats. ... involved with cellular recruitment, fever, acute.

  10. Isolating Lysosomes from Rat Liver.

    Science.gov (United States)

    Pryor, Paul R

    2016-04-01

    This protocol describes the generation of a fraction enriched in lysosomes from rat liver. The lysosomes are rapidly isolated using density-gradient centrifugation with gradient media that retain the osmolarity of the lysosomes such that they are functional and can be used in in vitro assays. © 2016 Cold Spring Harbor Laboratory Press.

  11. CCl4 cirrhosis in rats

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

    1991-01-01

    Cirrhosis of the rat liver was induced by a 12 week individualized CCl4/phenobarbital treatment. After treatment, all surviving animals (81%) showed cirrhosis of the liver. The cirrhosis induced was irreversible when evaluated 24 weeks after cessation of treatment. Quantitative liver function...

  12. Whiskers aid anemotaxis in rats.

    Science.gov (United States)

    Yu, Yan S W; Graff, Matthew M; Bresee, Chris S; Man, Yan B; Hartmann, Mitra J Z

    2016-08-01

    Observation of terrestrial mammals suggests that they can follow the wind (anemotaxis), but the sensory cues underlying this ability have not been studied. We identify a significant contribution to anemotaxis mediated by whiskers (vibrissae), a modality previously studied only in the context of direct tactile contact. Five rats trained on a five-alternative forced-choice airflow localization task exhibited significant performance decrements after vibrissal removal. In contrast, vibrissal removal did not disrupt the performance of control animals trained to localize a light source. The performance decrement of individual rats was related to their airspeed threshold for successful localization: animals that found the task more challenging relied more on the vibrissae for localization cues. Following vibrissal removal, the rats deviated more from the straight-line path to the air source, choosing sources farther from the correct location. Our results indicate that rats can perform anemotaxis and that whiskers greatly facilitate this ability. Because air currents carry information about both odor content and location, these findings are discussed in terms of the adaptive significance of the interaction between sniffing and whisking in rodents.

  13. Acute renal failure in rats

    International Nuclear Information System (INIS)

    Cederholm, C.; Almen, T.; Bergquist, D.; Golman, K.; Takolander, R.; Malmoe Allmaenna Sjukhus

    1989-01-01

    It was demonstrated in rats that renal injury which follows transient renal hypoxia is potentiated by the contrast media metrizoate, ioxaglate, iopamidol and iohexol. Intravenous injection of 1 g I/kg of all four media alone to 82 rats caused no significant increase in serum urea 1, 3 and 7 days later. The percentage increase of serum urea is given in median values and interquartile range (in parentheses). Bilateral renal arterial occlusion alone for 40 minutes in 42 rats increased serum urea one day later by 40% (20-130). Intravenous injection of the media followed in one hour by bilateral renal arterial occlusion for 40 minutes in 104 rats caused serum urea to increase one day later by 130% (70-350) after metrizoate, by 220% (50-380) after ioxaglate, by 290 % (60-420) after iopamidol and by 160% (50-330) after iohexol. There were no significant differences between the potentiating effects of the various media on ischemic renal failure. (orig.)

  14. August rats are more resistant to arrhythmogenic effect of myocardial ischemia and reperfusion than Wistar rats.

    Science.gov (United States)

    Belkina, L M; Kirillina, T N; Pshennikova, M G; Arkhipenko, Yu V

    2002-06-01

    As differentiated from Wistar rats, myocardial ischemia and reperfusion produce no ventricular fibrillation in August rats. Pretreatment with nitric oxide synthase inhibitor Nw-nitro-L-arginine increased mortality rate in August rats with acute myocardial infarction from 20 to 40%. Under these conditions mortality rate in Wistar rats increased from 50 to 71%. Interstrain differences in the resistance of these animals to the arrhythmogenic effect of ischemia are probably associated with higher activity of the nitric oxide system in August rats compared to Wistar rats.

  15. Diminished hormonal responses to exercise in trained rats

    DEFF Research Database (Denmark)

    Galbo, H; Richter, Erik; Holst, J J

    1977-01-01

    Male rats (120 g) either were subjected to a 12-wk physical training program (T rats) or were sedentary controls (C rats). Subsequently the rats were killed at rest or after a 45- or 90-min forced swim. At rest, T rats had higher liver and muscle glycogen concentrations but lower plasma insulin...

  16. Dithiobiuret toxicity in the rat

    International Nuclear Information System (INIS)

    Williams, K.D.

    1985-01-01

    Raising the daily dose of dithiobiuret (DTB) in male rats from 0.5 to 1 to 5 mg/kg shortened the latency to the onset of flaccid muscle tone and associated diminished performance in a treadmill test from 7 to 5 to 3 days, respectively. Concomitant with the development of flaccid muscle tone gastrocnemius muscle contractions elicited by high frequency motor nerve stimulation were lower in peak tension and tended to fade more rapidly in DTB-treated rats than in control rats. Remarkably, rats treated with highly daily doses (10-16 mg/kg) of DTB were resistant to the expected development of DTB-induced flaccid muscle tone, and tetanic contractile abnormalities but a corresponding refractoriness to body weight loss, decreased fed and water intake, diuresis, and depression in water balance was not present. This nonselectivity of the refractory responses supported the results of a histopathological study indicating that DTB-induced neuromuscular toxicity was unlikely to be secondary to effect on other organ systems. It is not known whether the ultimate neurotoxin is DTB or a metabolite. In this regard, two pathways for the metabolism of DTB were proposed based on the results of thin-layer chromatography of urine samples from rats treated with either 14 C- or 35 S-DTB. One pathway involved the reversible oxidation of DTB to the disulfide-containing compound thiuret, and the other involved the replacement of a sulfur atom with oxygen to form monothiobiuret. Thiuret, but not monothiobiuret, possessed comparable toxicity to STB. This further suggested that redox cycling between DTB and thiuret could be an important contributing factor to the toxicity of DTB

  17. Sexual dimorphism in hybrids rats.

    Science.gov (United States)

    Garcia-Falgueras, Alicia; Pinos, Helena; Fernández, Rosa; Collado, Paloma; Pasaro, Eduardo; Segovia, Santiago; Guillamon, Antonio

    2006-12-06

    Laboratory rat strains descend from Wistar rats as a consequence of artificial selection. Previously we reported that the medial posterior division of the bed nucleus of the stria terminalis (BSTMP) was sexually dimorphic in Wistar and Long-Evans strains while the medial anterior division (BSTMA) and the locus coeruleus (LC) only showed sex differences in the ancestor Wistar strain. The lateral posterior division (BSTLP) was isomorphic in both strains. The present work studies the number of neurons in the BSTMP, BSTMA, BSTLP and LC of male and female Wistar and Long-Evans rats (F(0)) and their hybrid F(1) and F(2) generations. The BSTMP is sexually dimorphic in the F(0), F(1) and F(2) generations while sex differences in the LC are only seen in F(0) Wistar rats but not in the F(0) Long-Evans or the F(1) and F(2) hybrid generations. Sex differences in the BSTMA are seen in F(0) Wistar but not in F(0) Long-Evans rats and completely disappear in the F(2) generations. The number of neurons in the LC of both males and females decreased in heterozygotic individuals (F(1)) but increased in homozygotic (F(2)). However, the number of neurons in the BSTMP changes significantly over the generations, although the ratio of neurons (female/male) is stable and unaffected in homo- or heterozygosis. Thus, the mechanism that regulates the neuronal female/male ratio would be different from the one that controls the number of neurons. The facts that sex differences in the BSTMP are not affected by homo- or heterozygosis and that they are seen in several mammalian orders suggest the existence of a "fixed" type of brain sex differences in the Mammalia Class.

  18. Inhibition of Corneal Neovascularization with the Combination of Bevacizumab and Plasmid Pigment Epithelium-Derived Factor-Synthetic Amphiphile INTeraction-18 (p-PEDF-SAINT-18 Vector in a Rat Corneal Experimental Angiogenesis Model

    Directory of Open Access Journals (Sweden)

    Ching-Hsein Chen

    2013-04-01

    Full Text Available Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups (Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and D: 10 μg + 10 μg of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 μg of p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV. The bFGF and PEDF genes were successfully expressed as shown by western blot analysis, and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival.Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonalantibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeabilityproperties. In this study, we demonstrated that the combination of bevacizumaband plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and

  19. Effects of heroin on rat prosocial behavior.

    Science.gov (United States)

    Tomek, Seven E; Stegmann, Gabriela M; Olive, M Foster

    2018-05-04

    Opioid use disorders are characterized in part by impairments in social functioning. Previous research indicates that laboratory rats, which are frequently used as animal models of addiction-related behaviors, are capable of prosocial behavior. For example, under normal conditions, when a 'free' rat is placed in the vicinity of rat trapped in a plastic restrainer, the rat will release or 'rescue' the other rat from confinement. The present study was conducted to determine the effects of heroin on prosocial behavior in rats. For 2 weeks, rats were given the opportunity to rescue their cagemate from confinement, and the occurrence of and latency to free the confined rat was recorded. After baseline rescuing behavior was established, rats were randomly selected to self-administer heroin (0.06 mg/kg/infusion i.v.) or sucrose pellets (orally) for 14 days. Next, rats were retested for rescuing behavior once daily for 3 days, during which they were provided with a choice between freeing the trapped cagemate and continuing to self-administer their respective reinforcer. Our results indicate that rats self-administering sucrose continued to rescue their cagemate, whereas heroin rats chose to self-administer heroin and not rescue their cagemate. These findings suggest that rats with a history of heroin self-administration show deficits in prosocial behavior, consistent with specific diagnostic criteria for opioid use disorder. Behavioral paradigms providing a choice between engaging in prosocial behavior and continuing drug use may be useful in modeling and investigating the neural basis of social functioning deficits in opioid addiction. © 2018 Society for the Study of Addiction.

  20. Genome Editing in Rats Using TALE Nucleases.

    Science.gov (United States)

    Tesson, Laurent; Remy, Séverine; Ménoret, Séverine; Usal, Claire; Thinard, Reynald; Savignard, Chloé; De Cian, Anne; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio

    2016-01-01

    The rat is an important animal model to understand gene function and model human diseases. Since recent years, the development of gene-specific nucleases has become important for generating new rat models of human diseases, to analyze the role of genes and to generate human antibodies. Transcription activator-like (TALE) nucleases efficiently create gene-specific knockout rats and lead to the possibility of gene targeting by homology-directed recombination (HDR) and generating knock-in rats. We describe a detailed protocol for generating knockout and knock-in rats via microinjection of TALE nucleases into fertilized eggs. This technology is an efficient, cost- and time-effective method for creating new rat models.

  1. Cerveau isolé and pretrigeminal rats.

    Science.gov (United States)

    Zernicki, B; Gandolfo, G; Glin, L; Gottesmann, C

    1984-01-01

    Cortical and hippocampal EEG activity was analysed in 14 cerveau isole and 8 pretrigerninal rats. In the acute stage, waking EEG patterns were absent in the cerveau isole, whereas sleep EEG patterns were absent in the pretrigeminal preparations. However, already on the second day the EEG waking-sleep cycle recovered in the majority of rats. Paradoxically, stimuli directed to the caudal part of preparations evoked stronger cortical and hippocampal EEG arousal than olfactory and visual stimuli. The behavior of the caudal part was observed in 25 preparations. Although in abortive form, the rats did show some locomotor and grooming behavior, and could be fed orally. The peripheral events of paradoxical sleep appeared only on the fourth or fifth day of survival of the cerveau isole rats. It is concluded that the activity of the isolated cerebrum of the rat is similar to that of cat preparations, but that functions of the caudal neuraxis are superior in rats.

  2. Pubertal neurocranium growth in thymectomized rats.

    Science.gov (United States)

    Rino, W; Teixeira, D

    1979-01-01

    Differences in neurocranium growth at puberty were studied in rats of both sexes thymectomized and sham-thymectomized at 2, 4, 6, 8, 10, 12 and 14 days of age and in controls of matched age and sex; skull length, width and height, and skull base length and face length were measured. The neurocranium of the thymectomized rats was significantly smaller than that of the sham-thymectomized and control rats of both sexes and in all age-groups.

  3. Treatment of diabetic rats with encapsulated islets

    OpenAIRE

    Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

    2008-01-01

    Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte? immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We enca...

  4. Rat bite fever in a pet lover.

    Science.gov (United States)

    Cunningham, B B; Paller, A S; Katz, B Z

    1998-02-01

    Rat-bite fever is an uncommon bacterial illness resulting from infection with Streptobacillus moniliformis that is often transmitted by the bite of a rat. The cutaneous findings in rat-bite fever are nonspecific but have been described as maculopapular or petechial. We describe a 9-year-old girl with acrally distributed hemorrhagic pustules, fever, and arthralgias. Diagnosis was delayed because of difficulty in identifying the pathologic organism. She was successfully treated with 10 days of ceftriaxone.

  5. Phosphodiesterases in the rat ovary

    DEFF Research Database (Denmark)

    Petersen, Tonny Studsgaard; Stahlhut, Martin; Andersen, Claus Yding

    2015-01-01

    that augmented cAMP levels stimulate primordial follicle growth. The present study examined the gene expression, enzyme activity and immunolocalization of the different cAMP hydrolysing PDEs families in the rat ovary. Further, the effect of PDE4 inhibition on primordial follicle activation in cultured neonatal......Phosphodiesterases (PDEs) are important regulators of the intracellular cAMP concentration, which is a central second messenger that affects a multitude of intracellular functions. In the ovaries, cAMP exerts diverse functions, including regulation of ovulation and it has been suggested...... rat ovaries was also evaluated. We found varied expression of all eight families in the ovary with Pde7b and Pde8a having the highest expression each accounting for more than 20% of the total PDE mRNA. PDE4 accounted for 15-26% of the total PDE activity. Immunoreactive PDE11A was found in the oocytes...

  6. Isolation of rat adrenocortical mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Solinas, Paola [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Fujioka, Hisashi [Electron Microscopy Facility, Department of Pharmacology, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Tandler, Bernard [Department of Biological Sciences, School of Dental Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Hoppel, Charles L., E-mail: charles.hoppel@case.edu [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

  7. Renal function in streptozotocin-diabetic rats

    DEFF Research Database (Denmark)

    Jensen, P K; Christiansen, J S; Steven, K

    1981-01-01

    to the rise in kidney glomerular filtration rate (diabetic rats: 37.0 nl/min; control rats: 27.9 nl/min). Likewise renal plasma flow was significantly higher in the diabetic rats (4.1 ml/min) than in the control group (3.0 ml/min). Glomerular capillary pressure was identical in both groups (56.0 and 56.0 mm......-1mmHg-1). Kidney weight was significantly higher in the diabetic rats (1.15 g; control rats: 0.96 g) while body weight was similar in both groups (diabetic rats: 232 g; control rats: 238 g). Calculations indicate that the increases in transglomerular hydraulic pressure, renal plasma flow......Renal function was examined with micropuncture methods in the insulin-treated streptozotocin-diabetic rat. Kidney glomerular filtration rate was significantly higher in the diabetic rats (1.21 ml/min) than in the control group (0.84 ml/min) Nephron glomerular filtration rate increased in proportion...

  8. X-ray lethality in diabetic rats

    International Nuclear Information System (INIS)

    Cember, H.; Thorson, T.M. Jr.

    1978-01-01

    Rats were made diabetic with streptozotocin and were irradiated with X-rays at various exposure levels in order to determine the LD-50/30 day dose. Non-diabetic control rats were exposed in a similar manner. The LD-50 exposures for the diabetic rats and the control rats were 436 R, and 617 R respectively. In view of the high prevalence of diabetes among the adult population, this finding may have important implications for diabetic workers who may be exposed accidentally to high levels of ionizing radiation

  9. Automatic Training of Rat Cyborgs for Navigation.

    Science.gov (United States)

    Yu, Yipeng; Wu, Zhaohui; Xu, Kedi; Gong, Yongyue; Zheng, Nenggan; Zheng, Xiaoxiang; Pan, Gang

    2016-01-01

    A rat cyborg system refers to a biological rat implanted with microelectrodes in its brain, via which the outer electrical stimuli can be delivered into the brain in vivo to control its behaviors. Rat cyborgs have various applications in emergency, such as search and rescue in disasters. Prior to a rat cyborg becoming controllable, a lot of effort is required to train it to adapt to the electrical stimuli. In this paper, we build a vision-based automatic training system for rat cyborgs to replace the time-consuming manual training procedure. A hierarchical framework is proposed to facilitate the colearning between rats and machines. In the framework, the behavioral states of a rat cyborg are visually sensed by a camera, a parameterized state machine is employed to model the training action transitions triggered by rat's behavioral states, and an adaptive adjustment policy is developed to adaptively adjust the stimulation intensity. The experimental results of three rat cyborgs prove the effectiveness of our system. To the best of our knowledge, this study is the first to tackle automatic training of animal cyborgs.

  10. Toxicity and repellency to rats of actidione

    Science.gov (United States)

    Traub, R.; DeWitt, J.B.; Welch, J.F.; Newman, D.

    1950-01-01

    The antibiotic actidione was found to be highly repellent to laboratory rats and to significantly reduce gnawing attacks upon treated paperboards. Rats refused to accept food or water containing this material even under conditions of acute starvation and died of starvation and thirst,rather than accept water containing l.0 mg. of actidione per liter. The compound is highly toxic to .rats with the minimum .lethal dose by oral administration being approximately l.0 mg./Kg body weight. Paperboard treated with the compound resisted gnawing attacks by specially trained and motivated rats for periods of two hundred hours, although similar .untreated boards were pierced within thirty-to sixty minutes.

  11. [Pharmacokinetics of crocetin in rats].

    Science.gov (United States)

    Liu, Tong-zheng; Qian, Zhi-yu

    2002-05-01

    To develop an HPLC method for the determination of crocetin in rat plasma and study the pharmacokinetics in rats. Hypersil C18 column (5 microns, 4.6 mm x 200 mm) was used at column temperature 30 degrees C. The mobile phase consisted of methanol-water-acetic acid (75:24.5:0.5) at the flow rate of 1.0 mL.min-1. The UV detection wave length was 423 nm. The calibration curve was linear (gamma = 0.9996) in the range from 0.49 microgram.mL-1 to 7.87 micrograms.mL-1 for crocetin. The mean recovery was 105.2%. The lowest detectable concentration of crocetin was 0.14 microgram.mL-1 (S/N = 3). The RSDs of within-day and between-day were all less than 5%. The plasma crocetin was steady. The HPLC method of determination of crocetin in the plasma was established. After single dose of 50 mg.kg-1 ig in 10 rats, the main pharmacokinetic parameters were estimated as follows: T1/2 alpha (30 +/- 6) min, Tmax(65 +/- 16) min, Cmax(5.0 +/- 1.0) microgram.mL-1, AUC0-T(845 +/- 109) microgram.min.mL-1, Vd(5.0 +/- 0.8) L.kg-1. Crocetin was shown to be absorbed into the blood through the gastrointestinal tract. This method is quick, precise and reliable. Crocetin was shown to be quickly absorbed in rats.

  12. Stevia preferences in Wistar rats.

    Science.gov (United States)

    Núñez Martínez, Paula; Argüelles Luis, Juan; Perillán Méndez, Carmen

    2016-11-01

    The Stevia rebaudiana plant is likely to become a major source of high-potency sweetener for the growing natural-food market. S. rebaudiana is the source of a number of sweet diterpenoid glycosides, but the major sweet constituents are rebaudioside A and stevioside. These two constituents have similar pharmacokinetic and metabolic profiles in rats and humans, and thus, studies carried out with either steviol glycoside are relevant to both. Other studies illustrate the diversity of voluntary sweet intake in mammals. This study was done using a series of two-bottle tests that compared a wide range of sweetener concentrations versus saccharin concentrations and versus water. Wistar rats displayed preferences for stevia extract and pure rebaudioside A solutions over water at a range of concentrations (0.001% to 0.3%), and their intake peak occurred at 0.1% concentration. They also preferred solutions prepared with a commercial rebaudioside A plus erythritol mixture to water, and their peak was at 2% concentration. The present study provides new information about the responses of Wistar rats to stevia compounds and commercial stevia products such as Truvia. These results could help with the appropriate dosage selection for focused behavioral and physiological studies on stevia.

  13. Polylysine-modified polyethylenimine (PEI-PLL) mediated VEGF gene delivery protects dopaminergic neurons in cell culture and in rat models of Parkinson's Disease (PD).

    Science.gov (United States)

    Sheikh, Muhammad Abid; Malik, Yousra Saeed; Xing, Zhenkai; Guo, Zhaopei; Tian, Huayu; Zhu, Xiaojuan; Chen, Xuesi

    2017-05-01

    Parkinson's Disease (PD) is a chronic neurodegenerative disorder characterized by motor deficits which result from the progressive loss of dopaminergic neurons. Gene therapy using growth factors such as VEGF seems to be a viable approach for potential therapeutic treatment of PD. In this study, we utilized a novel non-viral gene carrier designated as PEI-PLL synthesized by our laboratory to deliver VEGF gene to study its effect by using both cell culture as well as animal models of PD. For cell culture experiments, we utilized 6-hydroxydopamine (6-OHDA) mediated cell death model of MN9D cells following transfection with either a control plasmid or VEGF expressing plasmid. As compared to control transfected cells, PEI-PLL mediated VEGF gene delivery to MN9D cells resulted in increased cell viability, increase in the number of Tyrosine hydroxylase (TH) positive cells and decreased apoptosis following 6-OHDA insult. Next, we studied the therapeutic potential of PEI-PLL mediated VEGF gene delivery in SNPc by using unilateral 6-OHDA Medial forebrain bundle (MFB) lesion model of PD in rats. VEGF administration prevented the loss of motor functions induced by 6-OHDA as determined by behavior analysis. Similarly, VEGF inhibited the 6-OHDA mediated loss of DA neurons in Substantia Nigra Pars Compacta (SNPc) as well as DA nerve fibers in striatum as determined by TH immunostaining. In addition, PEI-PLL mediated VEGF gene delivery also prevented apoptosis and microglial activation in PD rat models. Together, these results clearly demonstrated the beneficial effects of PEI-PLL mediated VEGF gene delivery on dopaminergic system in both cell culture and animal models of PD. In this report, we exploited the potential of PEI-PLL to deliver VEGF gene for the potential therapeutic treatment of PD by using both cell culture and animal models of PD. To the best of our knowledge, this is the first report describing the use of novel polymeric gene carriers for the delivery of VEGF gene

  14. Identifying non-toxic doses of manganese for manganese-enhanced magnetic resonance imaging to map brain areas activated by operant behavior in trained rats.

    Science.gov (United States)

    Gálosi, Rita; Szalay, Csaba; Aradi, Mihály; Perlaki, Gábor; Pál, József; Steier, Roy; Lénárd, László; Karádi, Zoltán

    2017-04-01

    Manganese-enhanced magnetic resonance imaging (MEMRI) offers unique advantages such as studying brain activation in freely moving rats, but its usefulness has not been previously evaluated during operant behavior training. Manganese in a form of MnCl 2 , at a dose of 20mg/kg, was intraperitoneally infused. The administration was repeated and separated by 24h to reach the dose of 40mg/kg or 60mg/kg, respectively. Hepatotoxicity of the MnCl 2 was evaluated by determining serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, albumin and protein levels. Neurological examination was also carried out. The animals were tested in visual cue discriminated operant task. Imaging was performed using a 3T clinical MR scanner. T1 values were determined before and after MnCl 2 administrations. Manganese-enhanced images of each animal were subtracted from their baseline images to calculate decrease in the T1 value (ΔT1) voxel by voxel. The subtracted T1 maps of trained animals performing visual cue discriminated operant task, and those of naive rats were compared. The dose of 60mg/kg MnCl 2 showed hepatotoxic effect, but even these animals did not exhibit neurological symptoms. The dose of 20 and 40mg/kg MnCl 2 increased the number of omissions and did not affect the accuracy of performing the visual cue discriminated operant task. Using the accumulated dose of 40mg/kg, voxels with a significant enhanced ΔT1 value were detected in the following brain areas of the visual cue discriminated operant behavior performed animals compared to those in the controls: the visual, somatosensory, motor and premotor cortices, the insula, cingulate, ectorhinal, entorhinal, perirhinal and piriform cortices, hippocampus, amygdala with amygdalohippocampal areas, dorsal striatum, nucleus accumbens core, substantia nigra, and retrorubral field. In conclusion, the MEMRI proved to be a reliable method to accomplish brain activity mapping in correlation with the operant behavior

  15. Determination of rat vertebral bone compressive fatigue properties in untreated intact rats and zoledronic-acid-treated, ovariectomized rats

    NARCIS (Netherlands)

    Brouwers, J.E.M.; Ruchselman, M.; Rietbergen, van B.; Bouxsein, M.L.

    2009-01-01

    Summary Compressive fatigue properties of whole vertebrae, which may be clinically relevant for osteoporotic vertebral fractures, were determined in untreated, intact rats and zoledronic-acid-treated, ovariectomized rats. Typical fatigue behavior was found and was similar to that seen in other

  16. Modulation of rat behaviour by using a rat-like robot

    International Nuclear Information System (INIS)

    Shi, Qing; Ishii, Hiroyuki; Kinoshita, Shinichi; Takanishi, Atsuo; Okabayashi, Satoshi; Iida, Naritoshi; Kimura, Hiroshi; Shibata, Shigenobu

    2013-01-01

    In this paper, we study the response of a rat to a rat-like robot capable of generating different types of behaviour (stressful, friendly, neutral). Experiments are conducted in an open-field where a rat-like robot called WR-4 is put together with live rats. The activity level of each rat subject is evaluated by scoring its locomotor activity and frequencies of performing rearing (rising up on its hind limbs) and body grooming (body cuddling and head curling) actions, whereas the degree of preference of that is indicated by the robot–rat distance and the frequency of contacting WR-4. The moving speed and behaviour of WR-4 are controlled in real-time based on the feedback from rat motion. The activity level and degree of preference of rats for each experimental condition are analysed and compared to understand the influence of robot behaviour. The results of this study show that the activity level and degree of preference of the rat decrease when exposed to a stressful robot, and increase when the robot exhibit friendly behaviour, suggesting that a rat-like robot can modulate rat behaviour in a controllable, predictable way. (paper)

  17. Grooming behavior of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Buuse, M. van den; Jong, Wybren de

    1987-01-01

    In an open field spontaneously hypertensive rats (SHR) exhibited lower scores for grooming when compared to their normotensive controls, the Wistar Kyoto rats (WKY). After i.c.v. injection of 1 μg ACTH1–24 cumulative 50-min grooming scores were lower in SHR. Analysis of subscores indicated that the

  18. Morphological and neurohistological changes in adolescent rats ...

    African Journals Online (AJOL)

    Pregnancy was confirmed and the pregnant rats were divided into 3 groups based on the 3 trimesters (A, B, C), with each group having a control and a treated subgroup. The Control Groups (A1, B1, ... offspring of tobacco smokers. Keywords: Cortex, Histology, Prenatal nicotine, Adolescent rats, Neurological abnormalities ...

  19. Target-selected mutagenesis of the rat

    NARCIS (Netherlands)

    Smits, B.M.; Mudde, J.B.; Plasterk, R.; Cuppen, E.

    2004-01-01

    The rat is one of the most extensively studied model organisms, and with its genome being sequenced, tools to manipulate gene function in vivo have become increasingly important. We here report proof of principle for target-selected mutagenesis as a reverse genetic or knockout approach for the rat.

  20. Optical coherence tomography of the rat cochlea

    NARCIS (Netherlands)

    Wong, B. J. F.; de Boer, JF; Park, B.H.; Chen, ZP; Nelson, JS

    2000-01-01

    Optical coherence tomography (OCT) was used to image the internal structure of a rat cochlea (ex vivo). Immediately following sacrifice, the temporal bone of a Sprague-Dawley rat was harvested. Axial OCT cross sectional images lover regions of interest, 1x1 mm-2x8 mm) were obtained with a spatial

  1. Same-Different Categorization in Rats

    Science.gov (United States)

    Wasserman, Edward A.; Castro, Leyre; Freeman, John H.

    2012-01-01

    Same-different categorization is a fundamental feat of human cognition. Although birds and nonhuman primates readily learn same-different discriminations and successfully transfer them to novel stimuli, no such demonstration exists for rats. Using a spatial discrimination learning task, we show that rats can both learn to discriminate arrays of…

  2. in Alloxan-induced Diabetic Rats

    African Journals Online (AJOL)

    HP

    Group 4: Diabetic rats that were administered. 500 mg/kg body weight extracts. Group 5: Diabetic rats that were administered. 300 mg/kg body weight of metformin. The drug and extracts treatment was done for a period of 21 days using orogastric tube. Collection of blood samples. Following 21 days of extract administration, ...

  3. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: ... Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants, .... Of the 48 rats initially used in the current study, 5.

  4. Bromsulphalein (BSP) clearance in ageing rats

    NARCIS (Netherlands)

    Hollander, C.F.; Leeuw-Israel, F.R. de; Arp-Neefjes, J.M.

    1968-01-01

    Liver function in ageing rats was studied, using the bromsulphalein (BSP) clearance test. The test was done on ultramicro scale. This made it possible to repeat the test several times in the same animal and to start a longitudinal study. In 3-month-old rats the BSP retentions, measured 15, 30 and 45

  5. Adrenergic blockade in diabetic and uninephrectomized rats

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Jørgensen, P E

    1999-01-01

    The present study reports on the effects of adrenergic blocking agents on the renal growth and on the renal content and urinary excretion of epidermal growth factor (EGF) in streptozotocin-induced diabetic or uninephrectomized rats. Diabetic and uninephrectomized rats were allocated to groups...... treated with either saline or adrenergic antagonists and compared to controls and sham-operated controls, respectively. 24-hour urine samples were obtained on days 7, 14, and 21 and renal tissue samples on day 21. The 24-hour urinary excretion of EGF from controls and saline-treated diabetic rats...... was comparable. In adrenergic antagonist treated diabetic rats, it was reduced by at least 40% throughout the study period. Uninephrectomy caused a 50% reduction in the urinary excretion of EGF. This was not influenced by treatment with an adrenergic antagonist. After 3 weeks, saline-treated diabetic rats had...

  6. Transfer RNA methylases in rat placenta

    International Nuclear Information System (INIS)

    Jagtiani, S.K.; Narurkar, L.M.; Narurkar, M.V.

    1977-01-01

    Presence of tRNA methylases (5-adenosylmethionine : tRNA methyltransferases) was demonstrated at various stages of gestation in rat placenta, the enzyme being 50-100% higher than that of adult rat liver during early gestation. Placental tRNA methylases were shown to differ from those of liver in the extent of methylation. Glycine methyltransferase (S-adenosylmethionine : glycine methyltransferase), a regulatory enzyme in adult rat liver, was absent in placenta throughout gestation. The placental tRNA methylases could be inhibited in vitro by semipurified glycine methyltransferase from adult rat liver. The high placental tRNA methylase activity was comparable with the inhibitor-free enzyme activity of the adult rat liver. S-adenosyl-[Me- 14 C]-methionine was used in the investigation. (author)

  7. Development of ELISA kit for rat albumin

    International Nuclear Information System (INIS)

    Yuan Zhigang; Han Shiquan; Liu Yibing; Xu Wenge; Jia Juanjuan

    2009-01-01

    The Anti-rat albumin serum was prepared by immunized the sheep with rat albumin. A ELISA method was established for rat albumin. The measurement range of the assay was 1-50 mg/L, sensitivity of the assay was 0.42 mg/L, recovery rate was 85.0%-106.0%. Intra-and inter-assay variation coefficients were <8.9% and <12.8% respectively. The correlation coefficients between measured and expected values were 0.999 after serial dilution of the urine samples with high concentrations of rat albumin. A good correlation was observed between the ELISA and RIA methods, and the kit for rat albumin might provide a convenience in exploitation of renal drugs and experimental injury of the kidney. (authors)

  8. Metabolism of methylphenidate in dog and rat

    International Nuclear Information System (INIS)

    Egger, H.; Bartlett, F.; Dreyfuss, R.; Karliner, J.

    1981-01-01

    The urinary metabolites of methylphenidate in the dog and rat were investigated. After oral administration of 14C-labeled methylphenidate, approximately 86% and 63% of the dose was recovered in the urine of the dog and rat, respectively. Less than 1% of the dose was excreted as unchanged drug. Metabolism involved oxidation, hydrolysis, and conjugation processes. The primary hydrolytic product was alpha-phenyl-2-piperidineacetic acid (24%, dog; 35-40%, rat). The primary metabolites of oxidation were methyl 6-oxo-alpha-phenyl-2-piperidineacetate (3%, dog; 1.5%, rat) and the glucuronide of alpha-(p-hydroxyphenyl)-2-piperidineacetic acid (10%, rat). The former also underwent extensive biotransformation, including: 1) hydrolysis to the lactam acid (27%, dog; 7-10%, rat) and subsequent carboxylic acid O-glucuronidation (15%, dog); or 2) hydroxylation at the 5-position (1%, dog; 2%, rat) and subsequent hydrolysis (4%, dog; 15-17%, rat); or 3) 5-O-glucuronidation (12%, dog). Additional minor metabolites from methyl-6-oxo-alpha-phenyl-2-piperidineacetate were the phenolic O-glucuronide of methyl alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetate (1%, dog), and the 4-O-glucuronide of methyl 4-hydroxy-6-oxo-alpha-phenyl-2-piperidineacetate (1%, dog), and the taurine amide conjugate of alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetic acid (1%, dog). Additional products from methylphenidate conjugation included methyl 1-carbamoyl-alpha-phenyl-2-piperidineacetate (1%, dog or rat) and its carboxylic acid hydrolysis product (1%, rat). The chirality of the major metabolites isolated from dog urine showed that metabolism was partially stereoselective in all investigated cases, except in the formation of alpha-phenyl-2-piperidineacetic acid

  9. Genetic susceptibility to mammary carcinogenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

    1999-06-01

    The Copenhagen (COP) rat strain has previously been shown to be genetically resistant to chemical induction of breast cancer, while Wistar/Furth (WF) and Fischer 344 (F344) animals are relatively susceptible. We have compared the carcinogenic response of these three strains of rats to N-methyl-N-nitrosourea (MNU) with that to {sup 60}Co gamma rays. High incidences of mammary carcinomas were induced by MNU in the F344 and WF rats (100%), whereas the COP strain proved resistant (11.8%). In contrast, radiation-induced mammary carcinomas in COP rats developed in a similar incidence (37.0%) to those in the F344 (22.6%) and WF (26.9%) strains. The low incidence of papillary carcinomas in MNU-treated COP rats appeared to be directly related to the COP genetic resistance controlled by the Mcs genes. Ionizing radiation did, however, induce papillary carcinomas in all the three strains of rats. These carcinomas were more differentiated than MNU-induced cancers with regard to the two mammary differentiation markers, rat milk fat globule membrane (R-MFGM) and {alpha}-smooth muscle actin ({alpha}-SMA). Furthermore, ionizing radiation but not MNU induced mammary adenomas in all three strains, especially in COP rats. Such adenomas had differentiation marker profiles similar to these of carcinomas induced by {sup 60}Co gamma rays. When transplanted into syngenic hosts, growth of adenomas was 17 {beta}-estradiol (E{sub 2})-dependent and they progressed to carcinomas. Furthermore, one microcarcinoma was observed to develop from adenoma tissue in a radiation-exposed COP rat. The findings suggest that radiation and chemical carcinogens are likely to induce mammary cancers through different pathways or from different cell populations. The induction of relatively high incidences of mammary carcinomas and adenomas by radiation in COP rats may correlate with the genetically modulated and highly differentiated physiological status of their mammary glands. (author)

  10. Social exclusion intensifies anxiety-like behavior in adolescent rats.

    Science.gov (United States)

    Lee, Hyunchan; Noh, Jihyun

    2015-05-01

    Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Deep brain stimulation of the center median-parafascicular complex of the thalamus has efficient anti-parkinsonian action associated with widespread cellular responses in the basal ganglia network in a rat model of Parkinson's disease.

    Science.gov (United States)

    Jouve, Loréline; Salin, Pascal; Melon, Christophe; Kerkerian-Le Goff, Lydia

    2010-07-21

    The thalamic centromedian-parafascicular (CM/Pf) complex, mainly represented by Pf in rodents, is proposed as an interesting target for the neurosurgical treatment of movement disorders, including Parkinson's disease. In this study, we examined the functional impact of subchronic high-frequency stimulation (HFS) of Pf in the 6-hydroxydopamine-lesioned hemiparkinsonian rat model. Pf-HFS had significant anti-akinetic action, evidenced by alleviation of limb use asymmetry (cylinder test). Whereas this anti-akinetic action was moderate, Pf-HFS totally reversed lateralized neglect (corridor task), suggesting potent action on sensorimotor integration. At the cellular level, Pf-HFS partially reversed the dopamine denervation-induced increase in striatal preproenkephalin A mRNA levels, a marker of the neurons of the indirect pathway, without interfering with the markers of the direct pathway (preprotachykinin and preprodynorphin). Pf-HFS totally reversed the lesion-induced changes in the gene expression of cytochrome oxidase subunit I in the subthalamic nucleus, the globus pallidus, and the substantia nigra pars reticulata, and partially in the entopeduncular nucleus. Unlike HFS of the subthalamic nucleus, Pf-HFS did not induce per se dyskinesias and directly, although partially, alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced forelimb dyskinesia. Conversely, L-DOPA treatment negatively interfered with the anti-parkinsonian effect of Pf-HFS. Altogether, these data show that Pf-DBS, by recruiting a large basal ganglia circuitry, provides moderate to strong anti-parkinsonian benefits that might, however, be affected by L-DOPA. The widespread behavioral and cellular outcomes of Pf-HFS evidenced here demonstrate that CM/Pf is an important node for modulating the pathophysiological functioning of basal ganglia and related disorders.

  12. Oxidative stress of crystalline lens in rat menopausal model

    OpenAIRE

    Acer, Semra; Pekel, Gökhan; Küçükatay, Vural; Karabulut, Aysun; Yağcı, Ramazan; Çetin, Ebru Nevin; Akyer, Şahika Pınar; Şahin, Barbaros

    2016-01-01

    ABSTRACT Purpose: To evaluate lenticular oxidative stress in rat menopausal models. Methods: Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1). From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2), 10 were administered a daily injection of methylprednisolone until the end of the study (Gro...

  13. Dithiobiuret metabolism in the rat

    International Nuclear Information System (INIS)

    Williams, K.D.; Porter, W.R.; Peterson, R.E.

    1982-01-01

    Our main objective was to describe the metabolism of dithiobiuret (DTB) in the adult, male rat. Based on the thin-layer chromatographic analysis of urine from animals treated with [ 14 C] or [ 35 S] labeled DTB, two pathways for metabolism are proposed. One pathway is reversible and involves the oxidation of DTB to thiuret and the reduction of thiuret back to DTB. The other pathway consists of the desulfurization of DTB to monothiobiuret. The liver appears to desulfurate DTB because DTB-derived [35S] was eliminated from the liver more rapidly than [ 14 C]. The liver was the only tissue where the elimination kinetics of [ 35 S] and [ 14 C] DTB were different. DTB-derived radioactivity in urine that co-chromatographed with DTB, monothiobiuret, thiuret and sulfate was quantitated along with that of three uncharacterized metabolites. The presence of these unknown metabolites suggests that DTB metabolism is complex. The present study is the first description of the metabolic fate of DTB in the rat and serves as a starting point for determining whether DTB neurotoxicity is caused by the parent compound or a metabolite

  14. Lessons From Experiments in Rats

    Directory of Open Access Journals (Sweden)

    Albert Gramsbergen

    2001-01-01

    Full Text Available In this essay a few relevant aspects of the neural and behavioral development of the brain in the human and in the rat are reviewed and related to the consequences of lesions in the central and peripheral nervous system at early and later age. Movements initially are generated by local circuits in the spinal cord and without the involvement of descending projections. After birth, both in humans and in rats it seems that the devlopment of postural control is the limiting factor for several motor behaviors to mature. Strong indications exist that the cerebellum is significantly involved in this control. Lesions in the CNS at early stages interfere with fundamental processes of neural development, such as the establishment of fiber connections and cell death patterns. Consequently, the functional effects are strongly dependent on the stage of development. The young and undisturbed CNS, on the other hand, has a much greater capacity than the adult nervous system for compensating abnormal reinnervation in the peripheral nervous system. Animal experiments indicated that the cerebellar cortex might play an important part in this compensation. This possibility should be investigated further as it might offer important perspectives for treatment in the human.

  15. Autoprotection in acetaminophen intoxication in rats

    DEFF Research Database (Denmark)

    Dalhoff, K; Laursen, H; Bangert, K

    2001-01-01

    and liver tissue were collected before and 12, 24, 36, and 48 hr after the toxic dose and were analysed for hepatic glutathione and cysteine contents, hepatic glutathione-S-transferase and blood alanine aminotransferase activity, as well as acetaminophen concentration in plasma. Steady-state mRNA levels......Autoprotection by acetaminophen, i.e. increased resistance to toxic effects caused by pretreatment, is a well-known phenomenon. The purpose of the present work was to identify mechanisms for increased acetaminophen tolerance induced by pretreatment of rats. One group of female Wistar rats...... (pretreated rats) received acetaminophen orally in increasing doses (1 to 4.3 g/kg) twice a week for 3 weeks, one group (naïve rats) received the vehicle. At time zero pretreated rats received a toxic dose of 7.5 g/kg (100% lethal in naïve rats), and naïve rats received a toxic dose of 4.3 g/kg. Blood...

  16. Cerebral ammonia metabolism in hyperammonemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, A J; Mora, S N; Cruz, N F; Gelbard, A S

    1985-06-01

    The short-term metabolic fate of blood-borne (/sup 13/N)ammonia was determined in the brains of chronically (8- or 14-week portacaval-shunted rats) or acutely (urease-treated) hyperammonemic rats. Using a freeze-blowing technique it was shown that the overwhelming route for metabolism of blood-borne (/sup 13/N)ammonia in normal, chronically hyperammonemic and acutely hyperammonemic rat brain was incorporation into glutamine (amide). However, the rate of turnover of (/sup 13/N)ammonia to L-(amide-/sup 13/N)glutamine was slower in the hyperammonemic rat brain than in the normal rat brain. The activities of several enzymes involved in cerebral ammonia and glutamate metabolism were also measured in the brains of 14-week portacaval-shunted rats. The rat brain appears to have little capacity to adapt to chronic hyperammonemia because there were no differences in activity compared with those of weight-matched controls for the following brain enzymes involved in glutamate/ammonia metabolism: glutamine synthetase, glutamate dehydrogenase, aspartate aminotransferase, glutamine transaminase, glutaminase, and glutamate decarboxylase. The present findings are discussed in the context of the known deleterious effects on the CNS of high ammonia levels in a variety of diseases.

  17. Abstract numerical discrimination learning in rats.

    Science.gov (United States)

    Taniuchi, Tohru; Sugihara, Junko; Wakashima, Mariko; Kamijo, Makiko

    2016-06-01

    In this study, we examined rats' discrimination learning of the numerical ordering positions of objects. In Experiments 1 and 2, five out of seven rats successfully learned to respond to the third of six identical objects in a row and showed reliable transfer of this discrimination to novel stimuli after being trained with three different training stimuli. In Experiment 3, the three rats from Experiment 2 continued to be trained to respond to the third object in an object array, which included an odd object that needed to be excluded when identifying the target third object. All three rats acquired this selective-counting task of specific stimuli, and two rats showed reliable transfer of this selective-counting performance to test sets of novel stimuli. In Experiment 4, the three rats from Experiment 3 quickly learned to respond to the third stimulus in object rows consisting of either six identical or six different objects. These results offer strong evidence for abstract numerical discrimination learning in rats.

  18. Total parenteral nutrition in diabetic rats

    International Nuclear Information System (INIS)

    Norcross, E.D.; Stein, T.P.

    1986-01-01

    Parenteral Nutrition with hypertonic glucose is frequently given to diabetic patients. Large amounts of insulin can be required. The purpose of this investigation was to develop a totally parenterally nourished diabetic rat model. 200 g Female Sprague Dawley rats were made diabetic by i.v. injection of streptozotocin (50 mg/kg). Rats were then allowed to recover for at least 1 week before undergoing surgical insertion of a central venous catheter for parenteral feeding. TPN was begun 3 days after surgery. Prior to this they were allowed unlimited access to food and water. Control (non-streptozotocin treated) rats were run at the same time. Protein turnover was investigated by using 15 N glycine. Preliminary results: diabetic rats given mostly fat as a calorie source survived well in the absence of exogenous insulin whereas those that were given glucose only as their non-protein calorie source showed poor survival even with exogenous insulin. N balance and protein turnover in the lipid treated diabetic rats were comparable to the non-diabetic control rats

  19. Embryogenesis-promoting factors in rat serum.

    Science.gov (United States)

    Katoh, M; Kimura, R; Shoji, R

    1998-06-15

    Regarding whole rat embryo cultures in vitro, rat serum as a culture medium is known to support the normal growth of rat embryos in the organogenesis phase. The purpose of the present study was to isolate the embryogenesis-promoting factors from rat serum as a first step in the development of a defined serum-free medium for a whole embryo culture system. Pooled rat serum after heat inactivation was fractionated into three major peaks (frA, containing a region of void volume, frB, and frC) by gel filtration. The 9.5-day rat embryos that were cultivated for 48 hr in essential salt medium containing frB (with a molecular size range of 100-500 kDa) revealed normal growth. Three proteins (27 kDa, 76 kDa, and 190 kDa) that had the embryogenesis-promoting effects were isolated from 3-hr delayed centrifuged rat serum by the ion exchange chromatography. The 76-kDa protein was found to be rat transferrin by immunoblotting. The 27-kDa protein was identified as apo-AI (the major apoprotein of high-density lipoprotein) by immunoblotting. High-density lipoprotein obtained from pooled rat serum by a NaBr density gradient ultracentrifugation was found to have a positive effect on embryogenesis. The 10-kDa protein was also identified as alpha 1-inhibitor 3 by immunoblotting. In addition, the embryogenesis-promoting effect of the fraction containing 27-kDa and 190-kDa proteins declined within a short period of storage at -20 degrees C. This decrease was countered by supplementing its fraction (D-2) with albumin isolated from rat serum. These results in the present study suggest that transferrin, high-density lipoprotein, and alpha 1-inhibitor 3 in rat serum may be embryogenesis-promoting factors, and that albumin appeared to play a role in the embryogenesis of rat embryos in whole embryo cultures.

  20. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats.

    Science.gov (United States)

    Tanaka, Masami; Watanabe, Minoru; Yokomi, Izuru; Matsumoto, Naoki; Sudo, Katsuko; Satoh, Hitoshi; Igarashi, Tsuneo; Seki, Azusa; Amano, Hitoshi; Ohura, Kiyoshi; Ryu, Kakei; Shibata, Shunichi; Nagayama, Motohiko; Tanuma, Jun-ichi

    2015-01-01

    Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.

  1. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats

    Science.gov (United States)

    TANAKA, Masami; WATANABE, Minoru; YOKOMI, Izuru; MATSUMOTO, Naoki; SUDO, Katsuko; SATOH, Hitoshi; IGARASHI, Tsuneo; SEKI, Azusa; AMANO, Hitoshi; OHURA, Kiyoshi; RYU, Kakei; SHIBATA, Shunichi; NAGAYAMA, Motohiko; TANUMA, Jun-ichi

    2014-01-01

    Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats. PMID:25736479

  2. Ontogenic changes in selenite metabolism in rats

    International Nuclear Information System (INIS)

    Ostadalova, I.; Babicky, A.; Kopoldova, J.

    1982-01-01

    Radioselenium concentration and excretion was studied after administration of 75 Se-labelled selenite to male rats during ontogeny. The concentration of radioselenium in individual organs decreases with increasing age. The largest differences between young and adults were in the quantity and quality of excreted substances. During 2 h after the administration of 20 μmol selenite/kg young rats excreted 2.4% of the dose, essentially in the urine only, whilst adults excreted a total of 11%, distributed equally in breath and urine. The part excreted as methylated metabolites was 0.1% of the administered dose in young and 6.3% in adult rats. These results support the hypothesis that the differences in the sensitivity to the toxic action of selenite between young and adult rats can be due to ontogenic differences in selenium metabolism. (orig.)

  3. Tissue disposition of bifenthrin in the rat

    Data.gov (United States)

    U.S. Environmental Protection Agency — Tissue disposition of bifenthrin in the rat and oral and intravenous administration. This dataset is associated with the following publication: Hughes , M., D. Ross...

  4. Dietary GABA and food selection by rats.

    Science.gov (United States)

    Tews, J K; Repa, J J; Harper, A E

    1986-01-01

    To obtain further information pertaining to amino acid-induced alterations in feeding behavior, studies were performed to examine the food choices made by rats fed low protein diets made more or less aversive by the addition of various amino acids. When rats were allowed to choose between two diets, they preferred a low protein control, threonine-imbalanced or nonprotein diet to one containing 2.5% gamma-aminobutyric acid (GABA). Acceptance increased when GABA content was lowered to 1.5%; rats preferred this diet when the alternative diet was made sufficiently aversive. There were large individual differences among rats selecting from pairs of unacceptable diets. Avoidance of, or preference for, a given diet is clearly affected by the relative aversive qualities of the offered pair of diets.

  5. Experimental Salmonella typhimurium infections in rats. I

    DEFF Research Database (Denmark)

    Hougen, H P; Jensen, E T; Klausen, B

    1989-01-01

    The course of experimentally induced Salmonella typhimurium infection was studied in three groups of inbred LEW rats: homozygous +/+, athymic rnu/rnu and isogeneic thymus-grafted rnu/rnu rats. In the first experiment the animals were inoculated intraperitoneally with 10(8) bacteria and all animals...... became severely septicemic and died within a week of inoculation, irrespective of presence or absence of thymus. In the second experiment the animals were inoculated with 10(6) bacteria, and both euthymic and thymus-grafted animals responded with high titres of anti bacterial antibodies while these were...... very low in the athymic nude animals. Polyclonal antibody production was only observed in the euthymic animals and only regarding IgG. Athymic rats were not able to clear the infection, while the thymus-grafted animals reacted like euthymic rats: Very few animals housed the bacteria four weeks after...

  6. Black ginseng extract ameliorates hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Evelyn Saba

    2016-04-01

    Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  7. Reactive Protein Synthesis in Pregnant Rats

    African Journals Online (AJOL)

    olayemitoyin

    Department of Physiology, College of Medicine, University of Lagos, Nigeria. Summary: Genistein ... Oral exposure of pregnant rats to genistein precipitated hypothyroidism, altered some metabolic hormones with a ... consumption. Exposure to ...

  8. Tritium metabolism in rat tissues

    International Nuclear Information System (INIS)

    Takeda, H.

    1982-01-01

    As part of a series of studies designed to evaluate the relative radiotoxicity of various tritiated compounds, metabolism of tritium in rat tissues was studied after administration of tritiated water, leucine, thymidine, and glucose. The distribution and retention of tritium varied widely, depending on the chemical compound administered. Tritium introduced as tritiated water behaved essentially as body water and became uniformly distributed among the tissues. However, tritium administered as organic compounds resulted in relatively high incorporation into tissue constituents other than water, and its distribution differed among the various tissues. Moreover, the excretion rate of tritium from tissues was slower for tritiated organic compounds than for tritiated water. Administrationof tritiated organic compounds results in higher radiation doses to the tissues than does administration of tritiated water. Among the tritiated compounds examined, for equal radioactivity administered, leucine gave the highest radiation dose, followed in turn by thymidine, glucose, and water. (author)

  9. How rats combine temporal cues.

    Science.gov (United States)

    Guilhardi, Paulo; Keen, Richard; MacInnis, Mika L M; Church, Russell M

    2005-05-31

    The procedures for classical and operant conditioning, and for many timing procedures, involve the delivery of reinforcers that may be related to the time of previous reinforcers and responses, and to the time of onsets and terminations of stimuli. The behavior resulting from such procedures can be described as bouts of responding that occur in some pattern at some rate. A packet theory of timing and conditioning is described that accounts for such behavior under a wide range of procedures. Applications include the food searching by rats in Skinner boxes under conditions of fixed and random reinforcement, brief and sustained stimuli, and several response-food contingencies. The approach is used to describe how multiple cues from reinforcers and stimuli combine to determine the rate and pattern of response bouts.

  10. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  11. Epidermal growth factor reactivity in rat milk

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Tollund, L

    1990-01-01

    whey elutes as a broad peak corresponding to a Stokes radius of 4.0 nm (an approximate molecular weight of 80 kDa). Almost no 6 kDa EGF is present. Judged by gel filtration of whey pre-incubated with 125I-EGF (6 kDa), no binding protein for EGF is present in rat whey. When rat milk is incubated...

  12. Genetically determined differences in the resistance to myocardial infarction in Wistar and August rats.

    Science.gov (United States)

    Belkina, L M; Saltykova, V A; Pshennikova, M G

    2001-06-01

    In intact August rats, the cardiac contractile function at rest was by 76% higher than in Wistar rats, while their hearts, both intact and after acute myocardial infarction, were more resistant to isometric load than the hearts of Wistar rats. Postinfarction mortality in August rats was 18% vs. 70% in Wistar rats. Adrenoreactivity of the myocardium in August rats was decreased compared to that in Wistar rats. These peculiarities can determine high resistance of August rats to myocardial infarction.

  13. Factors influencing zinc bioavailability in rats

    International Nuclear Information System (INIS)

    Mahalko, J.R.; Johnson, P.E.; Swan, P.B.

    1986-01-01

    The amount of Zn fed, its source, and the Zn status of experimental animals may affect Zn bioavailability. To test this, rats were fed doses of Zn from ZnCl 2 or from various foods labeled extrinsically. Three weeks before and after the test meal, rats were fed an AIN diet modified in Zn content. Absorption was calculated by monitoring whole body retention and extrapolating to zero time. In rats fed 12 ppm Zn and test doses of 6 to 275 μg, absorption decreased from 80 to 50%, and the amount absorbed increased quadratically (r 2 = 0.998), but turnover was unaffected. Rats fed 38 or 77 ppm Zn absorbed less of test doses of 290, 613, or 1700 μg Zn than did those fed 12 ppm, and their Zn turnover rate was higher. In two 2 x 7 factorial experiments, rats fed 12 or 38 ppm Zn were given 16 or 98 μg Zn from 7 Zn sources. Bioavailability from some foods was higher than from ZnCl 2 except in rats eating only 12 ppm Zn and receiving the small dose. There were greater differences in bioavailability among foods when tested at the higher Zn status or dose. This may explain inconsistencies seen in comparing Zn bioavailability by traditional growth assay with that seen in 65 Zn tracer studies. The authors conclude that Zn status of the experimental animal, as well as the amount of Zn and its source, will affect Zn bioavailability

  14. Modifying factors in rat mammary gland carcinogenesis

    International Nuclear Information System (INIS)

    Shellabarger, C.J.

    1975-01-01

    The spontaneous incidence of mammary adenocarcinomas and mammary fibroadenomas in rats was found to be related to the strain of rat studied. Strains of rats that are sensitive to chemical carcinogens in regard to induced mammary neoplasia tend to be the same strains of rats that are sensitive to radiation. Methylcholantrene (MCA) and x-rays appeared to act in an additive fashion on the induction of mammary adenocarcinomas when they were given together. Lactating and older rats lose responsiveness to chemical carcinogens but do not lose responsiveness to radiation. Radiation appears to act in a scopal fashion in the induction of mammary neoplasia. Mammary neoplasia induction was not changed when low LET radiation was split into 2 equal fractions and high LET radiation was more effective than low LET radiation in inducing mammary neoplasia. It is suggested that DMBA can act as an initiator for the induction of mammary adenocarcinomas, that phorbol can act as a promotor, and that viruses may induce mammary neoplasia. Diethylstilbestrol (DES) and radiation appeared to act synergistically in the induction of mammary adenocarcinomas in one strain of rat but not in another strain. (U.S.)

  15. Diuron-induced rat bladder epithelial cytotoxicity.

    Science.gov (United States)

    Da Rocha, Mitscheli S; Arnold, Lora L; Pennington, Karen L; Muirhead, David; Dodmane, Puttappa R; Anwar, Muhammad M; Battalora, Michael; De Camargo, João Lauro V; Cohen, Samuel M

    2012-12-01

    Diuron, a substituted urea herbicide, is carcinogenic to the rat urinary bladder at high dietary levels (2500 ppm). To further elucidate the mode of action, this study aimed to determine the time course and sequence of bladder cytotoxic and proliferative changes induced by diuron treatment of male Wistar rats. Rats were randomized into two groups (control and 2500 ppm diuron) and treated for 28 days. Ten rats from each group were terminated on each of study days 1, 3, 7, or 28. Scanning electron micro scopy (SEM) showed urothelial cell swelling beginning on day 1, and by day 28, showed extensive necrosis, exfoliation and piling up of cells suggestive of hyperplasia. No difference in the bromo deoxyuridine labeling index was detected. In a second experiment, rats were randomized into control and diuron-treated groups and treated for 7 days or 8 weeks. After 7 days, transmission electron microscopy showed cell degenerative changes and distention of the cytoplasm, organelles, and nuclei characteristic of cytolysis. This resulted in protrusion of the superficial cells into the lumen, corresponding to the cell swelling observed previously by SEM. After 8 weeks, bladders in the diuron-treated group showed an increased incidence of simple hyperplasia by light microscopy (6/10, p diuron exposure in rats.

  16. Radiation nephropathy in young and adult rats

    International Nuclear Information System (INIS)

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-01-01

    The effects of bilateral kidney irradiation were compared in young and adult rats. During a 1 year period after a single dose of 0, 7.5, 10, 12.5, or 15 Gy on both kidneys, renal function (glomerular filtration rate and effective renal plasma flow), urine composition, and systolic blood pressure were measured periodically. The first changes after irradiation were observed in the glomerular filtration rate and urine osmolality. One month after 10, 12.5, and 15 Gy, glomerular filtration rate (GFR) and urine osmolality had declined below control values in the young rats. After this initial decline, renal function increased at control rate or even more during the third and fourth month after irradiation but decreased progressively thereafter. In the adult rats, GFR and urine osmolality started to decrease 3 months after 10, 12.5, and 15 Gy. A rise in systolic blood pressure and proteinuria started 2-3 months after 12.5 and 15 Gy in both age groups. Early changes in the glomerular filtration rate with a drop in urine osmolality in young rats, occurring during a period of rapid renal development indicated an irradiation-induced inhibition of glomerular and tubular development. Although renal function deteriorated at a later time in adult rats, dose-response relationships obtained in young and adult rats did not show significant differences

  17. Reproductive toxicity of Samanea tubulosa on rats

    Directory of Open Access Journals (Sweden)

    Maria Rafaella Luz de Araújo

    2015-12-01

    Full Text Available Samanea tubulosa is a plant used for medicinal and feeding purposes. However, ingestion of S. tubulosa pods has been associated with bovine abortion. Thus, the aim of this work was to investigate the effects of diet containing 5% of S. tubulosa pod meal on male and female Wistar rats. Diet was administered to male rats (n = 10 for 60 days before mating. Female rats (n = 10 received the treatment for 30 days, during cohabitation and from gestational day (GD 0 to GD20. Treated animals were mated with untreated rats. In male rats, plant consumption caused decreased food consumption and 20% fertility index reduction. Litters from treated males presented lower body weight and crown–rump length. Female rats treated with the plant increased water and food intake and body weight. Decreases in fertility, fecundity and gestation indices and increase of placenta weight and mean number of corpora lutea were found. Thus, owing to the possible general and reproductive toxic effects, long-term consumption of S. tubulosa is not recommended for phytotherapic or food purposes.

  18. Regulation of brain aromatase activity in rats

    International Nuclear Information System (INIS)

    Roselli, C.E.; Ellinwood, W.E.; Resko, J.A.

    1984-01-01

    The distribution and regulation of aromatase activity in the adult rat brain with a sensitive in vitro assay that measures the amount of 3 H 2 O formed during the conversion of [1 beta- 3 H]androstenedione to estrone. The rate of aromatase activity in the hypothalamus-preoptic area (HPOA) was linear with time up to 1 h, and with tissue concentrations up to 5 mgeq/200 microliters incubation mixture. The enzyme demonstrated a pH optimum of 7.4 and an apparent Michaelis-Menten constant (Km) of 0.04 microns. The greatest amount of aromatase activity was found in amygdala and HPOA from intact male rats. The hippocampus, midbrain tegmentum, cerebral cortex, cerebellum, and anterior pituitary all contained negligible enzymatic activity. Castration produced a significant decrease in aromatase activity in the HPOA, but not in the amygdala or cerebral cortex. The HPOAs of male rats contained significantly greater aromatase activity than the HPOAs of female rats. In females, this enzyme activity did not change during the estrous cycle or after ovariectomy. Administration of testosterone to gonadectomized male and female rats significantly enhanced HPOA aromatase activities to levels approximating those found in HPOA from intact males. Therefore, the results suggest that testosterone, or one of its metabolites, is a major steroidal regulator of HPOA aromatase activity in rats

  19. Radio protective effects of selenium on rats

    International Nuclear Information System (INIS)

    Bakir, A.; Alya, G

    2005-11-01

    Potential radio-protective effects of different selenium supplement concentrations of 4, 8, 15 and 30 ppm were evaluated in rats. Four groups of rats were administered different concentrations of selenium in drinking water for 30 days before irradiation starting from the ablactation which considered as day 0. The results showed that the sodium selenite of 4 ppm and 8 ppm enhance the 30-day survival of irradiated rats at 7 Gy ( sup 6 sup 0 Co source, whole body irradiation dose rate of 1 Gy x min sup - sup 1) compared to the control group. The mean cumulated probability of survival of rats was 69%+-6 (mean+-S.E.) and 77%+-6 in 4 and 8 ppm groups, respectively, versus 42%+-9 for control group (P<0.001). It was also indicated that sodium selenite with concentrations of 15 and 30 ppm had no significant reduction in mortality. The mean cumulated probability of survival of rats was 50%+-12 (P=0.39) and 49%+-14 (P=0.04), respectively. The toxic effects of selenium were observed at 15 ppm and 30 ppm, survivals after 30 days of selenium intake were 76% and 46%, respectively. It was concluded that 4 and 8 ppm sodium selenite have a radio-protective effect. 15 and 30 ppm sodium selenite had no radio-protective effects in rats, this may be due to a synergism of toxicity and radiation effects. (author)

  20. [Preventive effects of pueraria on presbycusis in rats].

    Science.gov (United States)

    Chen, Wangyan; Yao, Qi; Liu, Weihong; Zhang, Bibo; Wang, Ying; Liu, Bo

    2009-08-01

    To investigate the preventive effects of Pueraria on presbycusis in rats. Thirty-two 24-26 month old Wistar rats were randomly divided into four groups, and were treated with different dosages of Pueraria (1, 2, 4, 0 g x kg(-1) x d(-1)) separately for 4 weeks. Auditory brainstem response (ABR) was used to detect the change of hearing threshold of rats. Hemorheological items of rats were checked in each group. Compared with control group, the hearing threshold and hemorheological items of rats was significantly improved after treated with Pueraria (Ppresbycusis of rats.

  1. Fish oil versus arachis oil food supplementation in relation to pregnancy duration in rats

    DEFF Research Database (Denmark)

    Olsen, S.F.; Hansen, Harald S.; Jensen, B.

    1990-01-01

    Throughout pregnancy, Lewis rats were fed standard rat chow supplemented with 15% (w/w) of either MaxEPA fish oil (FO) or arachis oil (AO); a third group was fed standard rat chow only (St) (n = 15, 15, and 16 rats, respectively). Compared to AO-rats, FO-rats had substantially higher levels of n-3...

  2. Increased radiosensitivity of cerebral capillaries in neonatal Gunn rats as compared to Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Landolt, R.; Arn, D.

    1979-01-01

    The extent of petechial haemorrhages of the cerebral cortex examined between 14 hours and 4 days after X-irradiation to the head was compared in Sprague-Dawley and homozygous Gunn rats with congenital hyperbilirubinaemia. Animals 1 to 2 days old received single doses of either 250, 500 or 750 rad. By means of a special scoring scale the degree of the damage to the micro vasculature was semi-quantitatively estimated. In both strains a significant difference in effect was obtained between 250 and 500 rad, but not between 500 and 750 rad. The shape of the dose-effect curve in Gunn rats was similar to that of Sprague-Dawley rats, but displaced upwards. In Gunn rats the effect of 250 rad was greater that that of 750 rad in Sprague-Dawley rats. Possible radiosensitizing mechanisms are discussed with reference to the literature and these results. (author)

  3. Social structure predicts genital morphology in African mole-rats.

    Directory of Open Access Journals (Sweden)

    Marianne L Seney

    2009-10-01

    Full Text Available African mole-rats (Bathyergidae, Rodentia exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure.We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate.The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology.

  4. Social structure predicts genital morphology in African mole-rats.

    Science.gov (United States)

    Seney, Marianne L; Kelly, Diane A; Goldman, Bruce D; Sumbera, Radim; Forger, Nancy G

    2009-10-15

    African mole-rats (Bathyergidae, Rodentia) exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure. We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate. The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology.

  5. Automated registration of tail bleeding in rats.

    Science.gov (United States)

    Johansen, Peter B; Henriksen, Lars; Andresen, Per R; Lauritzen, Brian; Jensen, Kåre L; Juhl, Trine N; Tranholm, Mikael

    2008-05-01

    An automated system for registration of tail bleeding in rats using a camera and a user-designed PC-based software program has been developed. The live and processed images are displayed on the screen and are exported together with a text file for later statistical processing of the data allowing calculation of e.g. number of bleeding episodes, bleeding times and bleeding areas. Proof-of-principle was achieved when the camera captured the blood stream after infusion of rat whole blood into saline. Suitability was assessed by recording of bleeding profiles in heparin-treated rats, demonstrating that the system was able to capture on/off bleedings and that the data transfer and analysis were conducted successfully. Then, bleeding profiles were visually recorded by two independent observers simultaneously with the automated recordings after tail transection in untreated rats. Linear relationships were found in the number of bleedings, demonstrating, however, a statistically significant difference in the recording of bleeding episodes between observers. Also, the bleeding time was longer for visual compared to automated recording. No correlation was found between blood loss and bleeding time in untreated rats, but in heparinized rats a correlation was suggested. Finally, the blood loss correlated with the automated recording of bleeding area. In conclusion, the automated system has proven suitable for replacing visual recordings of tail bleedings in rats. Inter-observer differences can be eliminated, monotonous repetitive work avoided, and a higher through-put of animals in less time achieved. The automated system will lead to an increased understanding of the nature of bleeding following tail transection in different rodent models.

  6. Effect of radiation on rat skin collagen

    International Nuclear Information System (INIS)

    Nogami, Akira

    1980-01-01

    I. Albino male rats were exposed for 16 weeks to ultraviolet light (UVL) which has principle emission at 305 nm. There were no significant changes between control and UVL-exposed skins in the total hydroxyproline content. However, a little increase of citrate-soluble collagen, a little decrease of insoluble collagen and a decrease of aldehyde content in soluble collagen were observed with UVL exposure. Total acid glycosaminoglycan in skin increased 30% or more from control. These results show that the effect of UVL on rat skin in vivo was merely inflammation phenomenon and that the 'aging' process of skin was not caused in our experimental conditions. II. The effects of radiation on the solubility of rat skin collagen were examined under various conditions. 1) When intact rats were exposed to a single dose of radiation from 43 kVp X-ray source, the solubility in skin collagen did not change at 4,000 R dosage, while in irradiation of 40,000 R a decreased solubility in collagen was observed. When rats were given 400 R a week for 12 weeks, there was no changes in the solubility of collagen during experimental period. 2) In vitro exposure to skins, an irradiation of 40,000 R from 43 kVp X-ray source caused a decrease in the solubility of collagen. While an irradiation of 40,000 R of dosage from 200 kVp X-ray source resulted in the increase in soluble collagen and the decrease in insoluble collagen. 3) When intact rats were given a single dose of 40,000 R from 60 Co- gamma -ray, insoluble collagen decreased in both young and adult rats. Similar changes in collagen solubility were observed in vitro gamma -irradiation. (author)

  7. Stimulation of serotonin2C receptors elicits abnormal oral movements by acting on pathways other than the sensorimotor one in the rat basal ganglia.

    Science.gov (United States)

    Beyeler, A; Kadiri, N; Navailles, S; Boujema, M Ben; Gonon, F; Moine, C Le; Gross, C; De Deurwaerdère, P

    2010-08-11

    Serotonin2C (5-HT(2C)) receptors act in the basal ganglia, a group of sub-cortical structures involved in motor behavior, where they are thought to modulate oral activity and participate in iatrogenic motor side-effects in Parkinson's disease and Schizophrenia. Whether abnormal movements initiated by 5-HT(2C) receptors are directly consequent to dysfunctions of the motor circuit is uncertain. In the present study, we combined behavioral, immunohistochemical and extracellular single-cell recordings approaches in rats to investigate the effect of the 5-HT(2C) agonist Ro-60-0175 respectively on orofacial dyskinesia, the expression of the marker of neuronal activity c-Fos in basal ganglia and the electrophysiological activity of substantia nigra pars reticulata (SNr) neuron connected to the orofacial motor cortex (OfMC) or the medial prefrontal cortex (mPFC). The results show that Ro-60-0175 (1 mg/kg) caused bouts of orofacial movements that were suppressed by the 5-HT(2C) antagonist SB-243213 (1 mg/kg). Ro-60-0175 (0.3, 1, 3 mg/kg) dose-dependently enhanced Fos expression in the striatum and the nucleus accumbens. At the highest dose, it enhanced Fos expression in the subthalamic nucleus, the SNr and the entopeduncular nucleus but not in the external globus pallidus. However, the effect of Ro-60-0175 was mainly associated with associative/limbic regions of basal ganglia whereas subregions of basal ganglia corresponding to sensorimotor territories were devoid of Fos labeling. Ro-60-0175 (1-3 mg/kg) did not affect the electrophysiological activity of SNr neurons connected to the OfMC nor their excitatory-inhibitory-excitatory responses to the OfMC electrical stimulation. Conversely, Ro-60-0175 (1 mg/kg) enhanced the late excitatory response of SNr neurons evoked by the mPFC electrical stimulation. These results suggest that oral dyskinesia induced by 5-HT(2C) agonists are not restricted to aberrant signalling in the orofacial motor circuit and demonstrate discrete

  8. [Pinealectomy and early castration in the female Wistar rat].

    Science.gov (United States)

    Slama-Scemama, A

    1976-05-17

    Pinealectomy does not significantly modify the level of pituitary and plasma gonadotropins in intact and in castrated female Rats from brith to 75 days of age. Only the weight of the thyroid gland is higher in pinealectomized rats.

  9. Patterns of blood pressure variability in normotensive and hypertensive rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; He, J; Wagner, A J

    1995-01-01

    We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR)...... the day; less pronounced in 2K,1C; and not detectable in SHR. There are regular patterns of blood pressure fluctuations and specific modifications to the patterns by different forms of hypertension.......We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR...

  10. Classical clinical signs in rats experimemtally infected with Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Nwoha Rosemary Ijeoma Ogechi

    2015-02-01

    Full Text Available Objective: To investigate clinical signs in Trypanosoma brucei infection in albino rats. Methods: Fourteen rats grouped into 2 with 7 rats in each group were used to determine classical clinical manifestation of Trypanosoma brucei infection in rats. Group A rats were uninfected control and Group B rats were infected with Trypanosoma brucei. Results: Parasitaemia was recorded in Group B by (3.86±0.34 d and the peak of parasitaemia was observed at Day 5 post infection. Classical signs observed included squint eyes, raised whiskers, lethargy, no weight loss, pyrexia, isolation from the other rats, and starry hair coat. Conclusions: These signs could be diagnostic or aid in diagnosis of Trypanosoma brucei infection in rats.

  11. [Pituitary function of dysgenesic femal rats. Studies with grafting method].

    Science.gov (United States)

    Vanhems, E; Busquet, J

    1975-01-01

    Misulban administered to pregnant rats on the 15th day of gestation provoked gonadal dysgenesia in the offspring. Study of the pituitary function of dysgenesic female rats, realized by grafting method, showed gonadotrophic hypersecretion.

  12. Water metabolism and modification of tritium excretion in the rat

    International Nuclear Information System (INIS)

    Ichimasa, Y.; Akita, Y.

    1982-01-01

    1. The intake and excretion of tritium were studied in rats exposed to tritiated water vapor. The metabolism of tritium was also investigated in rats given single administrations of tritiated water and in rats given daily administrations (per os or i.p.). The results were essentially in accord with those reported previously. 2. Amounts of drinking water consumed and urine excreted by rats drinking water with 0.15% saccharin were 1.5 to 2 times higher than in rats drinking tap water. The tritium activity in various tissues of rats drinking water with 0.15% saccharin decreased to about half of that of rats drinking tap water. A similar tendency was observed also in rats drinking beer. The diuretic agent sodium acetazolamide also enhanced the urinary excretion of tritium. (author)

  13. Uptake of trace elements in adult and suckling rat lenses

    International Nuclear Information System (INIS)

    Nabekura, Tomohiro; Ito, Yoshimasa; Minami, Takeshi; Hirunuma, Rieko; Enomoto, Shuichi

    2001-01-01

    The uptake of trace elements in the lens was compared in adult and suckling rat lenses. Multitracers, including 15 trace elements, As, Be, Co, Fe, Mn, Rb, Rh, Ru, Sc, Se, Sr, Y, V, Zn, and Zr, were incubated with the lenses for 4 hr and their concentrations in the lens were measured. A high uptake rate of Zn was observed in the lenses of both adult and suckling rats in comparison with those of the other elements, and the Zn concentration in the lens of suckling rats was higher than that of adult rats. The uptake rate of Sr was higher in adult rats than in suckling rats. On the other contrary, Rb and Se concentrations in the lens were higher in suckling rats than in adult rats. The present study suggests that the different mechanisms depending on development serve to transport trace elements into the lens. (author)

  14. Absorption of plutonium in the iron-deficient rat

    International Nuclear Information System (INIS)

    Ragan, H.A.

    1977-01-01

    Iron deficiency did not enhance absorption of plutonium following intragastric gavage of rats. Absorption of plutonium citrate in both control and iron-deficient rats was about 0.03% of the administered dose

  15. (Urginea Altissima), Against the Field Rat, Arvicanthis Abyssinicus

    African Journals Online (AJOL)

    Bernt Lindtjorn

    the field rat, Arvicanthis abyssincus with the aim of developing locally based ... inhabited by humans and is commonly found in open ... rat, A. abyssinicus in a choice and non-choice tests. ..... sowing control of house mice (Mus domesticus):.

  16. Biochemical and Haematological Indices of Weanly Albino Rats Fed ...

    African Journals Online (AJOL)

    acer

    ABSTRACT: Malnutrition is a public health problem in Nigeria accounting for more than 50% of ... weanly albino rats using nutritional, biochemical ... groundnut (16%), soy beans (16%), crayfish ... consumption was observed in rats on PC and.

  17. Ulinastatin Reduces T Cell Apoptosis in Rats with Severe Acute ...

    African Journals Online (AJOL)

    in rats with severe acute pancreatitis (SAP) and to elucidate its underlying molecular mechanism. Methods: Thirty .... on T lymphocytes apoptosis in SAP rat model and elucidated ..... oxygen radicals, the exhaustion of adenine nucleotide and ...

  18. Healing effect of Shaoshang Yuhe yihao on burns in rats

    African Journals Online (AJOL)

    tissue expressions of transforming growth factor-beta (TGF-β) were determined along with skin histopathology. ... Polygonum cuspidatum Sieb. et Zucc., Aloe vera var. chinensis ... anesthetizing the rats after the rat hair was shaved. The top of ...

  19. Biological effects of 137Cs, incorporated into organism of rats

    International Nuclear Information System (INIS)

    Monakhov, A.S.; Strekalov, S.A.; Sokolov, A.V.; Aver'yanova, T.K.

    1987-01-01

    Results of investigating mutagenous and hemotoxic effects of 137 Cs on blood lymphocytes of rats are presented. 137 Cs was orally administrated into organism of rats as 270 kBq/g chloride solution. 137 Cs mutagenous effect was studied on metaphase plates of rat blood lymphocytes in course of rats lifetime experiment. It is stated that 137 Cs inducing severe disturbances of genetic material in a great quantity of blood lymphocytes, causes their total killing

  20. Tumorigenicity of sodium ascorbate in male rats.

    Science.gov (United States)

    Cohen, S M; Anderson, T A; de Oliveira, L M; Arnold, L L

    1998-06-15

    Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and bicarbonate, produces urinary alterations when fed at high doses to rats, which results in mild superficial urothelial cytotoxicity and regeneration but not tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low incidence of bladder tumors in rats if administered in a two-generation bioassay. In the present study, we evaluated sodium ascorbate in a two-generation bioassay that involved feeding to the male and female parental F344 rats for 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (at 28 days of age) male F1 generation rats for the remainder of their lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and 7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-responsive increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the short-term urothelial effects of sodium ascorbate in rats are inhibited by treatments producing urinary acidification to pH sodium ascorbate to evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus 2.78% NH4Cl in the diet was toxic, and the group was terminated early during the course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl showed complete inhibition of the urothelial effects of sodium ascorbate and significant inhibition of its renal effects. We also demonstrated the presence of a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate at all doses, in a dose-responsive manner. The formation of the precipitate was inhibited by coadministration with NH4Cl. The proliferative effects of sodium ascorbate on the male rat

  1. From engineering to editing the rat genome.

    Science.gov (United States)

    Meek, Stephen; Mashimo, Tomoji; Burdon, Tom

    2017-08-01

    Since its domestication over 100 years ago, the laboratory rat has been the preferred experimental animal in many areas of biomedical research (Lindsey and Baker The laboratory rat. Academic, New York, pp 1-52, 2006). Its physiology, size, genetics, reproductive cycle, cognitive and behavioural characteristics have made it a particularly useful animal model for studying many human disorders and diseases. Indeed, through selective breeding programmes numerous strains have been derived that are now the mainstay of research on hypertension, obesity and neurobiology (Okamoto and Aoki Jpn Circ J 27:282-293, 1963; Zucker and Zucker J Hered 52(6):275-278, 1961). Despite this wealth of genetic and phenotypic diversity, the ability to manipulate and interrogate the genetic basis of existing phenotypes in rat strains and the methodology to generate new rat models has lagged significantly behind the advances made with its close cousin, the laboratory mouse. However, recent technical developments in stem cell biology and genetic engineering have again brought the rat to the forefront of biomedical studies and enabled researchers to exploit the increasingly accessible wealth of genome sequence information. In this review, we will describe how a breakthrough in understanding the molecular basis of self-renewal of the pluripotent founder cells of the mammalian embryo, embryonic stem (ES) cells, enabled the derivation of rat ES cells and their application in transgenesis. We will also describe the remarkable progress that has been made in the development of gene editing enzymes that enable the generation of transgenic rats directly through targeted genetic modifications in the genomes of zygotes. The simplicity, efficiency and cost-effectiveness of the CRISPR/Cas gene editing system, in particular, mean that the ability to engineer the rat genome is no longer a limiting factor. The selection of suitable targets and gene modifications will now become a priority: a challenge where

  2. Opiates and cerebral functional activity in rats

    International Nuclear Information System (INIS)

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid [1- 14 C] octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions

  3. Working Memory Systems in the Rat.

    Science.gov (United States)

    Bratch, Alexander; Kann, Spencer; Cain, Joshua A; Wu, Jie-En; Rivera-Reyes, Nilda; Dalecki, Stefan; Arman, Diana; Dunn, Austin; Cooper, Shiloh; Corbin, Hannah E; Doyle, Amanda R; Pizzo, Matthew J; Smith, Alexandra E; Crystal, Jonathon D

    2016-02-08

    A fundamental feature of memory in humans is the ability to simultaneously work with multiple types of information using independent memory systems. Working memory is conceptualized as two independent memory systems under executive control [1, 2]. Although there is a long history of using the term "working memory" to describe short-term memory in animals, it is not known whether multiple, independent memory systems exist in nonhumans. Here, we used two established short-term memory approaches to test the hypothesis that spatial and olfactory memory operate as independent working memory resources in the rat. In the olfactory memory task, rats chose a novel odor from a gradually incrementing set of old odors [3]. In the spatial memory task, rats searched for a depleting food source at multiple locations [4]. We presented rats with information to hold in memory in one domain (e.g., olfactory) while adding a memory load in the other domain (e.g., spatial). Control conditions equated the retention interval delay without adding a second memory load. In a further experiment, we used proactive interference [5-7] in the spatial domain to compromise spatial memory and evaluated the impact of adding an olfactory memory load. Olfactory and spatial memory are resistant to interference from the addition of a memory load in the other domain. Our data suggest that olfactory and spatial memory draw on independent working memory systems in the rat. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Gastric secretion elicited by conditioning in rats.

    Science.gov (United States)

    Caboclo, José Liberato Ferreira; Cury, Francico de Assis; Borin, Aldenis Albanese; Caboclo, Luís Otávio Sales Ferreira; Ribeiro, Maria Fernanda Sales Caboclo; de Freitas, Pedro José; Andersson, Sven

    2009-01-01

    To investigate whether interdigestive gastric acid secretion can be controlled by a possible memory-related cortical mechanism. To evaluate gastric secretion in rats, we used a methodology that allows gastric juice collection in rats in their habitual conditions (without any restraining) by pairing sound as the conditioning stimulus (CS) and food as the unconditioning stimulus (US). The levels of gastric acid secretion under basal conditions and under sound stimulation were recorded and the circulating gastrin levels determined. When the gastric juice was collected in the course of the conditioning procedure, the results showed that under noise stimulation a significant increase in gastric acid secretion occurred after 10 days of conditioning (p<0.01). The significance was definitively demonstrated after 13 days of conditioning (p<0.001). Basal secretions of the conditioned rats reached a significant level after 16 days of conditioning. The levels of noise-stimulated gastric acid secretion were the highest so far described in physiological experiments carried out in rats and there were no significant increases in the circulating gastrin levels. The results point to the important role played by cortical structures in the control of interdigestive gastric acid secretion in rats. If this mechanism is also present in humans, it may be involved in diseases caused by inappropriate gastric acid secretion during the interprandial periods.

  5. Opiates and cerebral functional activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.

  6. Hematological changes in opium addicted diabetic rats.

    Science.gov (United States)

    Asadikaram, Gholamreza; Sirati-Sabet, Majid; Asiabanha, Majid; Shahrokhi, Nader; Jafarzadeh, Abdollah; Khaksari, Mohammad

    2013-01-01

    Chronic opioid treatment in animal models has shown to alter hematological parameters. The aim of this study was to evaluate the biological effects of opium on the number of peripheral blood cells and red blood cells (RBCs) indices in diabetic rats. Peripheral blood samples were collected from diabetic, opium-addicted, diabetic opium-addicted and normal male and female rats and hematological parameters were measured. The mean number of white blood cells (WBCs) was significantly higher in diabetic opium-addict females compared to diabetic non-addict female group. In both male and female, the mean number of neutrophils was significantly higher and the mean number of lymphocytes was lower in diabetic opium-addicted rats than those observed in diabetic non-addicted group. In diabetic opium-addicted male group the mean counts of RBC significantly increased as compared with diabetic male group. However, in diabetic addicted female, the mean number of RBCs was significantly lower than diabetic non-addicted female group. In both males and females, the mean number of platelets was significantly lower in diabetic addict rats compared to diabetic non-addict group. Generally, the results indicated that opium addiction has different effects on male and female rats according to the number of WBC, RBC and RBC indices. It could also be concluded that in the opium-addicts the risk of infection is enhanced due to the weakness of immune system as a result of the imbalance effect of opium on the immune cells.

  7. Cardiopulmonary Changes with Moderate Decompression in Rats

    Science.gov (United States)

    Robinson, R.; Little, T.; Doursout, M.-F.; Butler, B. D.; Chelly, J. E.

    1996-01-01

    Sprague-Dawley rats were compressed to 616 kPa for 120 min then decompressed at 38 kPa/min to assess the cardiovascular and pulmonary responses to moderate decompression stress. In one series of experiments the rats were chronically instrumented with Doppler ultrasonic probes for simultaneous measurement of blood pressure, cardiac output, heart rate, left and right ventricular wall thickening fraction, and venous bubble detection. Data were collected at base-line, throughout the compression/decompression protocol, and for 120 min post decompression. In a second series of experiments the pulmonary responses to the decompression protocol were evaluated in non-instrumented rats. Analyses included blood gases, pleural and bronchoalveolar lavage (BAL) protein and hemoglobin concentration, pulmonary edema, BAL and lung tissue phospholipids, lung compliance, and cell counts. Venous bubbles were directly observed in 90% of the rats where immediate post-decompression autopsy was performed and in 37% using implanted Doppler monitors. Cardiac output, stroke volume, and right ventricular wall thickening fractions were significantly decreased post decompression, whereas systemic vascular resistance was increased suggesting a decrease in venous return. BAL Hb and total protein levels were increased 0 and 60 min post decompression, pleural and plasma levels were unchanged. BAL white blood cells and neutrophil percentages were increased 0 and 60 min post decompression and pulmonary edema was detected. Venous bubbles produced with moderate decompression profiles give detectable cardiovascular and pulmonary responses in the rat.

  8. Somatostatin ontogenesis in the gastrointestinal and pancreatic tract: study in normal rats and during a induced diabetes in neonates rats

    International Nuclear Information System (INIS)

    Cunha, M.C.

    1980-01-01

    The ontogenic studies of somatostatin of pancreas, ileum and duodenum of Wistar rats and the rats with induced diabetes were done. The radioimmunologic method to dose the somatostatin was used. (L.M.J.)

  9. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Tadashi Okamura

    2013-01-01

    Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

  10. Effect of Yushen zhuyun decoction on rats with diminished ovarian ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Yushen zhuyun decoction (YSZYF) on rats with diminished ovarian reserve (DOR). Methods: High-performance liquid chromatography (HPLC) was used to determine the major phytochemical constituents of YSZYF. Rats with DOR (DOR rats) were prepared by administration of ...

  11. Haematological and Serum Biochemical Variables in rats Treated ...

    African Journals Online (AJOL)

    The haematology and serum biochemical effects of oral administration of the ethanolic extract of the root of Moringa oleifera at 50, 100 and 150 mg/kg were investigated in 30 mated female Wistar rats. The rats were assigned into five groups of six rats each. Group A was given 50mg/kg of the extract; group B, 100mg/kg; ...

  12. Activation of peripheral leukocytes in rat pregnancy and experimental preeclampsia

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Linton, EA; Sargent, IL; Redman, CWG

    OBJECTIVE: The aim of this study was to search for activation markers of peripheral leukocytes in experimental preeclampsia in the rat. STUDY DESIGN: Experimental preeclampsia was induced in 14-day-pregnant rats by infusion of endotoxin (1.0 mu g/kg body weight). For comparison, rats with normal

  13. Effects of Culling on Leptospira interrogans Carriage by Rats

    Science.gov (United States)

    Byers, Kaylee A.; Donovan, Christina M.; Bidulka, Julie J.; Stephen, Craig; Patrick, David M.; Himsworth, Chelsea G.

    2018-01-01

    We found that lethal, urban rat control is associated with a significant increase in the odds that surviving rats carry Leptospira interrogans. Our results suggest that human interventions have the potential to affect and even increase the prevalence of zoonotic pathogens within rat populations. PMID:29350160

  14. ( Cola Nitida Rubra ) on Reproductive Hormones in Rats

    African Journals Online (AJOL)

    Our previous study suggests that aqueous extract of kola nut had effect on reproductive hormones in male rats. This study evaluates the effects of kola nut extract on plasma level of testosterone and luteinizing hormones in male rats. 30 adult male rats were used. These were divided into three groups: group A served as ...

  15. Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes

    NARCIS (Netherlands)

    Price, R.J.; Scott, M.P.; Walters, D.G.; Stierum, R.H.; Groten, J.P.; Meredith, C.; Lake, B.G.

    2004-01-01

    The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets

  16. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

    Directory of Open Access Journals (Sweden)

    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  17. Regulation of Taurine transporter activity in cultured rat retinal ganglion cells and rat retinal Muller Cells

    International Nuclear Information System (INIS)

    Eissa, Laila A.; Smith, Sylvia B.; El-sherbeny, Amira A.

    2006-01-01

    Diabetic retinopathy is one of the most common complications of diabetes. The amino acid taurine is believed to play an antioxidant protective role in diabetic retinopathy through the scavenging of the reactive species. It is not well established whether taurine uptake is altered in retina cells during diabetic conditions. Thus, the present study was designed to investigate the changes in taurine transport in cultures of rat retinal Muller cells and rat retinal ganglion cells under conditions associated with diabetes. Taurine was abundantly taken up by retinal Muller cells and rat retinal ganglion cells under normal glycemic condition. Taurine was actively transported to rat Muller cells and rat retinal ganglion cells in a Na and Cl dependant manner. Taurine uptake further significantly elevated in both type of cells after the incubation with high glucose concentration. This effect could be attributed to the increase in osmolarity. Because Nitric Oxide (NO) is a molecule implicated in the pathogenesis of diabetes, we also determined the activity of taurine transporter in cultured rat retinal Muller cells and rat retinal ganglion cells in the presence of the NO donors, SIN-1 and SNAP. Taurine uptake was elevated above control value after 24-h incubation with low concentration of NO donors. We finally investigated the ability of neurotoxic glutamate to change taurine transporter activity in both types of cells. Uptake of taurine was significantly increased in rat retinal ganglion cells when only incubated with high concentration of glutamate. Our data provide evidence that taurine transporter is present in cultured rat retinal ganglion and Muller cells and is regulated by hyperosmolarity. The data are relevant to disease such as diabetes and neuronal degeneration where retinal cell volume may dramatically change. (author)

  18. Threonine phosphorylation of rat liver glycogen synthase

    International Nuclear Information System (INIS)

    Arino, J.; Arro, M.; Guinovart, J.J.

    1985-01-01

    32 P-labeled glycogen synthase specifically immunoprecipitated from 32 P-phosphate incubated rat hepatocytes contains, in addition to [ 32 P] phosphoserine, significant levels of [ 32 P] phosphothreonine. When the 32 P-immunoprecipitate was cleaved with CNBr, the [ 32 P] phosphothreonine was recovered in the large CNBr fragment (CB-2, Mapp 28 Kd). Homogeneous rat liver glycogen synthase was phosphorylated by all the protein kinases able to phosphorylate CB-2 in vitro. After analysis of the immunoprecipitated enzyme for phosphoaminoacids, it was observed that only casein kinase II was able to phosphorylate on threonine and 32 P-phosphate was only found in CB-2. These results demonstrate that rat liver glycogen synthase is phosphorylated at threonine site(s) contained in CB-2 and strongly indicate that casein kinase II may play a role in the ''in vivo'' phosphorylation of liver glycogen synthase. This is the first protein kinase reported to phosphorylate threonine residues in liver glycogen synthase

  19. Iron appetite and latent learning in rats.

    Science.gov (United States)

    Woods, S C; Vasselli, J R; Milam, K M

    1977-11-01

    Two experiments are reported which show that rats are capable of forming an association between the presence of iron in a solution when it is not specifically needed and a subsequent state of iron deficiency. Specifically, rats were trained to lever press for water while thirsty. One group received ferrous ions in addition to the water. When these rats were subsequently rendered iron deficient, they lever pressed more under extinction conditions as a graded function of lower hemoglobin levels. Controls that either did not receive ferrous ions during training or received solutions other than ferrous solutions during training did not respond this way under extinction conditions. This is therefore a type of latent learning previously demonstrated only for sodium appetite.

  20. Metabolic neural mapping in neonatal rats

    International Nuclear Information System (INIS)

    DiRocco, R.J.; Hall, W.G.

    1981-01-01

    Functional neural mapping by 14 C-deoxyglucose autoradiography in adult rats has shown that increases in neural metabolic rate that are coupled to increased neurophysiological activity are more evident in axon terminals and dendrites than neuron cell bodies. Regions containing architectonically well-defined concentrations of terminals and dendrites (neuropil) have high metabolic rates when the neuropil is physiologically active. In neonatal rats, however, we find that regions containing well-defined groupings of neuron cell bodies have high metabolic rates in 14 C-deoxyglucose autoradiograms. The striking difference between the morphological appearance of 14 C-deoxyglucose autoradiograms obtained from neonatal and adult rats is probably related to developmental changes in morphometric features of differentiating neurons, as well as associated changes in type and locus of neural work performed

  1. Helminth parasites in black rats (Rattus rattus) and brown rats (Rattus norvegicus) from different environments in the Netherlands

    NARCIS (Netherlands)

    Franssen, Frits; Swart, Arno; van Knapen, Frans|info:eu-repo/dai/nl/070114749; van der Giessen, Joke

    2016-01-01

    BACKGROUND: Rattus norvegicus (brown rat) and Rattus rattus (black rat) are known carriers of bacteria, viruses, and parasites of zoonotic and veterinary importance. Moreover, rats may play a role in the transmission of muscle larvae of the zoonotic nematode Trichinella spiralis to farm animals. We

  2. Neutron irradiation of rat embryos in utero

    International Nuclear Information System (INIS)

    Vogel, H.H. Jr.

    1978-01-01

    In the rat radiation is most effective in producing congenital anomalies during the organ-forming period (days 9 to 13), which is approximately equivalent to the 14th to 50th days of human pregnancy. We have exposed female Sprague--Dawley rats on the 18th day of pregnancy to single whole-body doses of fission neutrons (20 to 150 rads). After 20 rads there was a small decrease in body weight which lasted from birth to weaning. During this period 9% of the irradiated rats died compared with 4% of the controls. After 50 rads, 65/275 (23.6%) of the rats died between birth and weaning, and the body-weight loss of the survivors was increased. After 100 rads, 62/133 (47%) died at birth or day 1 and 103/133 (77.4%) died before weaning. A large and significant decrease in body weight persisted in the survivors. After 150 rads of fission neutrons, all 95 rats died within 48 hr of birth. From cross-fostering experiments, we believe this is a direct effect of radiation on the embryos and not an indirect action through the mother or her milk. The LD 50 for the period from birth to weaning is approximately 75 rads of fission neutrons. Studies of organ weight were conducted daily for the first week after birth in an attempt to find the cause of radiation mortality. Body weight of the irradiated animals averaged only about one-half that of the controls. The liver, kidney, brain, and testes of the neutron-irradiated rats weighed significantly less than those of the controls. The weights of the spleen, lungs, duodenum, and stomach were decreased but not significantly. The bone marrow appeared depleted in the irradiated long bones, but the spleen maintained active hematopoiesis 1 to 2 months after neutron exposure

  3. Oxidative stress in normal and diabetic rats.

    Science.gov (United States)

    Torres, M D; Canal, J R; Pérez, C

    1999-01-01

    Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (pC18:2) ratios. Greater vitaminE/triglyceride (TG) ratio, however, appeared in the control group. The corresponding vitamin A ratios (vitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected.

  4. Renal alterations in prediabetic rats with periodontitis

    DEFF Research Database (Denmark)

    Andersen, Carla Cruvinel Pontes; Holmstrup, Palle; Buschard, Karsten

    2008-01-01

    BACKGROUND: Periodontitis was shown to have an impact on glucose levels in prediabetic and diabetic rats. The Zucker fatty rat (ZFR) is a well-characterized model of prediabetes presenting with impaired glucose tolerance, hyperinsulinemia, dyslipidemia, and moderate hypertension. The aim...... IValpha1, fibronectin, and nephrin. Urinary albumin excretion and creatinine clearance were also evaluated. RESULTS: In prediabetic ZFRs, periodontitis was associated with kidney hypertrophy (P = 0.03) and a tendency for increased glomerular volume (P = 0.06). In lean littermates, elevated fibronectin m...

  5. Immunity to Fasciola hepatica in the rat

    International Nuclear Information System (INIS)

    Armour, J.; Dargie, J.D.

    1974-01-01

    Experiments were carried out which demonstrated an acquired immunity to Fasciola hapatica in the rat. It was shown that this immunity could be transferred to recipients using either lymphoid cells or serum from infected donor rats. The extent of the protection obtained by cells appeared to be related to the quantity and persistence of the antigenic stimulus in the donor. Likewise, the degree of immunity conferred by immune serum was dependent upon the volume transferred. The significance of these results in relation to the mechanism of immunity to fascioliasis is discussed

  6. Characterization of rat lung ICAM-1

    DEFF Research Database (Denmark)

    Beck-Schimmer, B; Schimmer, R C; Schmal, H

    1998-01-01

    studies, rat pulmonary artery endothelial cells (RPAEC), rat alveolar macrophages and aortic rings were stimulated (as described below) and evaluated for ICAM-1 expression. TREATMENT: RPAEC and macrophages were stimulated with lipopolysaccharide (LPS) and recombinant murine tumour necrosis factor alpha...... peaked at 4 h, while lung ICAM- I protein peaked at 6 h. CONCLUSIONS: Quantitation of ICAM-1 expression in vitro and in vivo suggests that ICAM-1 plays a central role in two lung inflammatory models. Furthermore, lung ICAM-1 upregulation involves at least two cell types: vascular endothelial cells...

  7. Absorption of pentacaine from ulcerous rat stomach

    International Nuclear Information System (INIS)

    Tomcikova, O.; Babulova, A.; Durisova, M.; Trnovec, T.; Benes, L.

    1985-01-01

    Pentacaine is a local anaesthetic which exhibited positive effects on healing of model ulcers in the rat stomach. The in situ disappearance of pentacaine from the ulcerous and intact rat stomach was studied. Gastric ulcers were produced by oral administration of phenylbutazone (200 mg/kg) 3.5 h before absorption experiment. Pentacaine exhibited a biexponential decrease from the lumen of the stomach, the rate of which was essentially the same in both groups. The total amount of pentacaine absorbed was small because of extremly low absorption rate. (author)

  8. Fenbendazole treatment and litter size in rats.

    Science.gov (United States)

    Johnston, Nancy A; Bieszczak, Jeremiah R; Verhulst, Steven; Disney, Kimberly E; Montgomery, Kyle E; Toth, Linda A

    2006-11-01

    Fenbendazole is commonly used in laboratory animal medicine as an anthelmintic for elimination of pinworms. It is generally regarded as a safe drug with minimal side effects. In our facility, 2 breeding colonies of rats were treated with fenbendazole to eliminate pinworms. Analysis of the breeding records revealed that feeding Sprague-Dawley rats a diet containing fenbendazole on a continuous basis for 7 consecutive weeks was associated with a significant reduction in litter size. Although the mechanism underlying this effect is unknown, the finding prompts caution when using fenbendazole to treat valuable breeding colonies or strains that are poor breeders.

  9. The oncogenic action of ionizing radiation on rat skin

    International Nuclear Information System (INIS)

    Burns, F.J.

    1991-01-01

    Progress has occurred in several areas corresponding to the specific aims of the proposal: (1) Progression and multiple events in radiation carcinogenesis of rat skin as a function of LET; (2) cell cycle kinetics of irradiated rat epidermis as determined by double labeling and double emulsion autoradiography; (3) oncogene activation detected by in situ hybridization in radiation-induced rat skin tumors; (4) amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of LET; and (5) transformation of rat skin keratinocytes by ionizing radiation in combination with c-Ki-ras and c-myc oncogenes. 111 refs., 13 figs., 12 tabs

  10. Rats demonstrate helping behavior toward a soaked conspecific.

    Science.gov (United States)

    Sato, Nobuya; Tan, Ling; Tate, Kazushi; Okada, Maya

    2015-09-01

    Helping behavior is a prosocial behavior whereby an individual helps another irrespective of disadvantages to him or herself. In the present study, we examined whether rats would help distressed, conspecific rats that had been soaked with water. In Experiment 1, rats quickly learned to liberate a soaked cagemate from the water area by opening the door to allow the trapped rat into a safe area. Additional tests showed that the presentation of a distressed cagemate was necessary to induce rapid door-opening behavior. In addition, it was shown that rats dislike soaking and that rats that had previously experienced a soaking were quicker to learn how to help a cagemate than those that had never been soaked. In Experiment 2, the results indicated that rats did not open the door to a cagemate that was not distressed. In Experiment 3, we tested behavior when rats were forced to choose between opening the door to help a distressed cagemate and opening a different door to obtain a food reward. Irrespective of how they learned to open the door, in most test trials, rats chose to help the cagemate before obtaining a food reward, suggesting that the relative value of helping others is greater than the value of a food reward. These results suggest that rats can behave prosocially and that helper rats may be motivated by empathy-like feelings toward their distressed cagemate.

  11. [Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

    Science.gov (United States)

    Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

    2017-12-01

    Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

  12. Effect of x-irradiation in rats bearing walker-256-carcinosarcoma and normal rats

    International Nuclear Information System (INIS)

    Ehara, Kazuhiko

    1978-01-01

    Serum protein fractions and total proteins were studied with bloods obtained from the rats exposed each to the partial-, whole-bodies and the transplanted tumors (Walker-256-carcinosarcoma transplanted in the right hind leg). The electrophoretic variation induced in the sera of tumor-bearing rats (Group II), and the content of total proteins decreased. Early irradiation to the tumor part of rats less induced the variations of the electrophoretic pattern and the decrease of the amount of serum total proteins. When the distant metastasis appeared during irradiation treatment, the electrophoretic patterns and content of total proteins changed proportionally to the variation in sera of Group II. On the other hand, the γ-globulin (G) fraction increased in the long-term survival rat. The separation of the rat serum β-G into two peaks of β 1 - and β 2 -G was shown only in Group IV (late irradiation to the right hind leg). This finding supposed that some factors involve in the sera of rats with transplanted primary tumor grown up to a fixed size and guessed the appearance of the distant metastasis during x-irradiation. The percentages of the albumin and γ-G decreased slightly and those of the α 1 -, α 2 - and β-G increased slightly in the rats with 300 rad partial-body (the right hind leg) x-irradiation daily for 20 days. The remarkable decrease of the albumin and γ-G, the increase of the α 1 - and β-G, the marked increase of the α 2 -G and the decrease of serum total proteins were demonstrated for the sera of rats with 1,000 rad whole-body x-irradiation at a time. These phenomena seem to be related to the destructive and reticuloendothelial injury by the exposure. (auth.)

  13. Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats

    Czech Academy of Sciences Publication Activity Database

    Holubová, Martina; Zemenová, Jana; Mikulášková, Barbora; Panajotová, V.; Stöhr, J.; Haluzík, M.; Kuneš, Jaroslav; Železná, Blanka; Maletínská, Lenka

    2016-01-01

    Roč. 229, č. 2 (2016), s. 85-96 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * lipidization * diet-induced obesity * ZDF rats * food intake * rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.706, year: 2016

  14. Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats

    Czech Academy of Sciences Publication Activity Database

    Holubová, M.; Zemenová, J.; Mikulášková, Barbora; Panajotová, V.; Stöhr, J.; Haluzík, M.; Kuneš, Jaroslav; Železná, B.; Maletínská, L.

    2016-01-01

    Roč. 229, č. 2 (2016), s. 85-96 ISSN 0022-0795 R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : prolactin-releasing peptide * lipidization * diet-induced obesity * ZDF rats * food intake rat Subject RIV: ED - Physiology Impact factor: 4.706, year: 2016

  15. Efficacy and Safety of Gwakhyangjeonggi-San Retention Enema in Normal Rats and Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Eunyoung Song

    2013-01-01

    Full Text Available The purpose of this study is to establish a protocol of retention-enema experiments and evaluate the antihypertensive effect and the safety of Gwakhyangjeonggi-san retention enema. Normal and spontaneously hypertensive rats (SHRs were divided into treatment and control groups, respectively. We applied the Gwakhyangjeonggi-san extract by decoction and 0.9% NaCl in each group, estimated the blood pressure and body weight, and performed HPLC analysis. ALT, AST, BUN, and creatinine were examined. The systolic blood pressure within each group in normal rats differed significantly in time effect, and so did the diastolic blood pressure in the treatment group of normal rats. The systolic, diastolic, and mean blood pressure showed significant differences in group effect in the treatment group of the SHRs. The time effect of the body weight in both groups of normal rats differed significantly, so did group × time and time effects in both groups of SHRs. AST, ALT, BUN, and creatinine showed no significant difference between groups. We concluded that the Gwakhyangjeonggi-san retention enema has a hypotensive effect in normal rats within the regular range of blood pressure, but an antihypertensive effect in SHRs. Also, the intervention is safe and does not affect the liver and kidney functions in normal rats.

  16. Rats do not eat alone in public: Food-deprived rats socialize rather than competing for baits.

    Directory of Open Access Journals (Sweden)

    Omri Weiss

    Full Text Available Limited resources result in competition among social animals. Nevertheless, social animals also have innate preferences for cooperative behavior. In the present study, 12 dyads of food-deprived rats were tested in four successive trials, and then re-tested as eight triads of food-deprived rats that were unfamiliar to each other. We found that the food-deprived dyads or triads of rats did not compete for the food available to them at regular spatially-marked locations that they had previously learnt. Rather, these rats traveled together to collect the baits. One rat, or two rats in some triads, lead (ran ahead to collect most of the baits, but "leaders" differed across trials so that, on average, each rat ultimately collected similar amounts of baits. Regardless of which rat collected the baits, the rats traveled together with no substantial difference among them in terms of their total activity. We suggest that rats, which are a social species that has been found to display reciprocity, have evolved to travel and forage together and to share limited resources. Consequently, they displayed a sort of 'peace economy' that on average resulted in equal access to the baits across trials. For social animals, this type of dynamics is more relaxed, tolerant, and effective in the management of conflicts. Rather than competing for the limited available food, the food-deprived rats socialized and coexisted peacefully.

  17. Juvenile female rats, but not male rats, show renewal, reinstatement, and spontaneous recovery following extinction of conditioned fear.

    Science.gov (United States)

    Park, Chun Hui J; Ganella, Despina E; Kim, Jee Hyun

    2017-12-01

    Anxiety disorders emerge early, and girls are significantly more likely to develop anxiety compared to boys. However, sex differences in fear during development are poorly understood. Therefore, we investigated juvenile male and female rats in the relapse behaviors following extinction of conditioned fear. In all experiments, 18-d-old rats first received three white-noise-footshock pairings on day 1. On day 2, extinction involved 60 white-noise alone trials. In experiment 1, we examined renewal by testing the rats in either the same or different context as extinction on day 3. Male rats did not show renewal, however, female rats showed renewal. Experiment 2 investigated reinstatement by giving rats either a mild reminder footshock or context exposure on day 3. When tested the next day, male rats did not show reinstatement, whereas female rats showed reinstatement. Experiment 3 investigated spontaneous recovery by testing the rats either 1 or 5 d following extinction. Male rats did not show any spontaneous recovery whereas female rats did. Taken together, fear regulation appear to be different in males versus females from early in development, which may explain why girls are more prone to suffer from anxiety disorders compared to boys. © 2017 Park et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Extracellular ATP induces albuminuria in pregnant rats

    NARCIS (Netherlands)

    Faas, M.M.; van der Schaaf, G.; Borghuis, T.; Jongman, R.M.; van Pampus, Maria; de Vos, P.; van Goor, Harry; Bakker, W.W.

    BACKGROUND: As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. METHODS: Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 microg/kg bw) via a permanent jugular vein cannula.

  19. Gastric emptying of oils in the rat

    International Nuclear Information System (INIS)

    Palin, K.J.; Whalley, D.R.; Wilson, C.G.; Phillips, A.J.; Davis, S.S.

    1982-01-01

    Sulphur colloid, labelled with technetium 99 and emulsified with arachis oil, miglyol 812 or liquid paraffin, was administered orally to male rats. A gamma camera, linked to a computer was used for imaging for 108 mins. after administration. The efficiency of the oils to aid stomach emptying was compared and arachis oil found to be the most effective. (U.K.)

  20. Spatial Memory in Spontaneously Hypertensive Rats (SHR)

    NARCIS (Netherlands)

    Sontag, Thomas-A.; Fuermaier, Anselm B. M.; Hauser, Joachim; Kaunzinger, Ivo; Tucha, Oliver; Lange, Klaus W.

    2013-01-01

    The spontaneously hypertensive rat (SHR) is an established animal model of ADHD. It has been suggested that ADHD symptoms arise from deficits in executive functions such as working memory, attentional control and decision making. Both ADHD patients and SHRs show deficits in spatial working memory.

  1. Developmental neurotoxicity of Propylthiouracil in rats

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Hansen, P.; Christiansen, S.

    2007-01-01

    early in pregnancy may cause adverse effects on the offspring. This has led to increased concern about thyroid hormone disrupting chemicals (TDCs) in our environment. We have studied how developmental exposure to the known antithyroid agent propylthiouracil (PTU) affects the development of rat pups...... behaviour and hearing function. This supports that exposure to TDC's in general may cause long-lasting developmental neurotoxicity....

  2. Estrogen induces glomerulosclerosis in analbuminemic rats

    NARCIS (Netherlands)

    Joles, JA; van Goor, H; Koomans, HA

    Progression of chronic renal disease: is usually more rapid in males, both In humans and in experimental animals. Estrogen-replacement studies indicate that this may be related to the beneficial effects of estrogen on the lipoprotein profile. However, in hyperlipidemic analbuminemic rats (NAR),

  3. DNA isolation from rat tail or ear

    NARCIS (Netherlands)

    Cuppen, E.

    2010-01-01

    This protocol describes a rapid procedure for isolating DNA from rat tail or ear punches. The simplest version of the protocol can be scaled for use in 96-well (deep-well) plates. The quality of the DNA is sufficient for any polymerase chain reaction (PCR)-based genotyping approach.

  4. Gastrointestinal absorption of Np in rats

    International Nuclear Information System (INIS)

    Wirth, R.; Volf, V.

    1985-01-01

    The effect of Np mass and the acidity of the administered Np solutions as well as the age, sex and nutritional status of the animals injected or gavaged with 239Np or 237Np were determined. The latter factor proved to be dominant for absorption of Np from the gut. Thus in fasting weanling and young adult male rats, the absorption of 239Np was sixfold higher (0.18% and 0.12%, respectively) than in fed ones (0.03% and 0.02%, respectively). Absorption by fasted adult females was 0.05% of the administered 239Np, about half of that of adult males. Raising the Np-mass gavaged to fasted female rats to 1 and 10 mg 237Np/kg resulted in an absorption of 0.23% and 0.26%, respectively. Thus, an increased absorption of Np in adult rats seems to be expected only if a large mass is ingested. No dependence of the absorption of Np on nitric acid concentration was found. The data obtained after oral administration of 238Pu and 239Np to adult rats suggest that the f1 factor recommended by the ICRP for fractional absorption of soluble Np compounds from the gut should be decreased, whereas the f1 factor for soluble Pu compounds should be raised

  5. Rat Lungworm Expands into North America

    Centers for Disease Control (CDC) Podcasts

    2016-01-21

    Emily York, integrated pest management specialist at the Sam Noble Museum of Natural History, discusses the rat lungworm expansion in North America.  Created: 1/21/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/21/2016.

  6. Sequential causal learning in humans and rats

    NARCIS (Netherlands)

    Lu, H.; Rojas, R.R.; Beckers, T.; Yuille, A.; Love, B.C.; McRae, K.; Sloutsky, V.M.

    2008-01-01

    Recent experiments (Beckers, De Houwer, Pineño, & Miller, 2005;Beckers, Miller, De Houwer, & Urushihara, 2006) have shown that pretraining with unrelated cues can dramatically influence the performance of humans in a causal learning paradigm and rats in a standard Pavlovian conditioning paradigm.

  7. Episodic-like memory in the rat.

    Science.gov (United States)

    Babb, Stephanie J; Crystal, Jonathon D

    2006-07-11

    A fundamental question in comparative cognition is whether animals remember unique, personal past experiences. It has long been argued that memories for specific events (referred to as episodic memory) are unique to humans. Recently, considerable evidence has accumulated to show that food-storing birds possess critical behavioral elements of episodic memory, referred to as episodic-like memory in acknowledgment of the fact that behavioral criteria do not assess subjective experiences. Here we show that rats have a detailed representation of remembered events and meet behavioral criteria for episodic-like memory. We provided rats with access to locations baited with distinctive (e.g., grape and raspberry) or nondistinctive (regular chow) flavors. Locations with a distinctive flavor replenished after a long but not a short delay, and locations with the nondistinctive flavor never replenished. One distinctive flavor was devalued after encoding its location by prefeeding that flavor (satiation) or by pairing it with lithium chloride (acquired taste aversion), while the other distinctive flavor was not devalued. The rats selectively decreased revisits to the devalued distinctive flavor but not to the nondevalued distinctive flavor. The present studies demonstrate that rats selectively encode the content of episodic-like memories.

  8. A microculture technique for rat lymphocyte transformation.

    Science.gov (United States)

    Lindsay, V J; Allardyce, R A

    1979-01-01

    We report the development of an economical microculture technique suitable for measuring rat lymphocyte response to mitogens and in mixed lymphocyte reactions. The effects of varying culture conditions, i.e. source of serum, addition and concentration of 2-mercaptoethanol, mitogen concentrations, culture incubation times, absorption of serum, lymphocyte numbers and microtitre plate well shape are described.

  9. In Utero Hepatocellular Transplantation in Rats

    Directory of Open Access Journals (Sweden)

    Emma Muñoz-Sáez

    2013-01-01

    Full Text Available This work represents a step forward in the experimental design of an in utero hepatocellular transplantation model in rats. We focused on the enrichment optimization of isolated fetal hepatocytes suspension, arranging the surgery methodology of in utero transplantation, monitoring the biodistribution of the transplanted hepatocytes, and assessing the success of the transplants. Rat fetuses have been transplanted at the 17th embryonic day (ED17 with fetal hepatocytes isolated from rats at the end of pregnancy (ED21. We assessed possible differences between lymphocyte population, CD4 positive, CD8 positive, double-positive T-cells, and anti-inflammatory cytokines interleukins 4 and 10 (IL4 and IL10 as well. Cellular viability reached the rates of 90–95%. Transplanted groups had a limited success. Transplanted hepatocytes were not able to pass through the hematoplacental barrier. The hepatocytes injected were primarily located in the liver. There was an upward trend in the whole amount of T CD4 and T CD8 cells. There was an increased IL4 in the transplanted groups observed in the pregnant rats. The possibility to induce tolerance in fetuses with a hepatocyte transplant in utero could be a key point to avoid the immunosuppression treatments which must be undergone by transplanted patients.

  10. Transfer of memory retrieval cues in rats.

    Science.gov (United States)

    Briggs, James F; Fitz, Kelly I; Riccio, David C

    2007-06-01

    Two experiments using rats were conducted to determine whether the retrieval of a memory could be brought under the control of new contextual cues that had not been present at the time of training. In Experiment 1, rats were trained in one context and then exposed to different contextual cues immediately, 60 min, or 120 min after training. When tested in the shifted context, rats that had been exposed shortly after training treated the shifted context as if it were the original context. The control that the previously neutral context had over retrieval disappeared with longer posttraining delays, suggesting the importance of an active memory representation during exposure. Experiment 2 replicated the basic finding and demonstrated that the transfer of retrieval cues was specific to the contextual cues present during exposure. These findings with rats are consistent with findings from infant research (see, e.g., Boller & Rovee-Collier, 1992) that have shown that a neutral context can come to serve as a retrieval cue for an episode experienced elsewhere.

  11. Oxytocin biotransformation in the rat limbic brain

    NARCIS (Netherlands)

    Burbach, J.P.H.; Schotman, P.; Kloet, E.R. de

    2006-01-01

    Two peptide fragments of oxytocin were isolated by high-pressure liquid chromatography from digests of oxytocin obtained after exposure to a SPM preparation of the rat limbic brain. The structures of these peptides, being Gln-Asn-Cys(O)x-Pro-Leu-GlyNH2 and Gln-Asn-Cys(-S-S-Cys)-Pro-Leu-GlyNH2, were

  12. Taurine content of tissues of irradiated rats

    International Nuclear Information System (INIS)

    Akhalaya, M.Ya.; Bogatyrev, G.P.; Kudryashov, Yu.B.; Yartsev, E.I.

    1976-01-01

    The taurine content of tissues (liver, stomach, small intestine and spleen) of rats irradiated with doses of 700 and 450 rads has been studied. Phase changes have been found in the taurine content of radiosensitive tissues in the course of radiation injury development

  13. Serum testosterone concentration in chloroquine- treated rats ...

    African Journals Online (AJOL)

    ONOS

    2010-07-05

    Jul 5, 2010 ... The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone ... chloroquine are probably mediated via the generation of free radicals. ... Effects of ascorbic acid and alpha-tocopherol on serum testosterone concentration in chloroquine-treated rats. Groups.

  14. Morphological and neurohistological changes in adolescent rats ...

    African Journals Online (AJOL)

    olayemitoyin

    Pregnancy was confirmed and the pregnant rats were divided into 3 groups based on the 3 trimesters ... form of attention deficit hyperactive disorder characterised by ..... Yoshinaga K., Rice C., Krenn J., Pilot R.L. (1979). Effects of nicotine on ...

  15. Toluene depresses plasma corticosterone in pregnant rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Hansen, A. M.; Hass, Ulla

    2003-01-01

    of corticosteroids from the maternal to the foetal compartment. Pregnant rats were subjected to either 1500 ppm toluene 6 hr/day and/or a schedule of "Chronic mild stress" during the last two weeks of gestation. Exposure to toluene was associated with reduced birth weight and lower maternal weight gain, the latter...

  16. METABOLISM AND DOSIMETRY OF VINCLOZOLIN IN RAT

    Science.gov (United States)

    Vinclozolin (V) is an agricultural fungicide. V administered to rats is hydrolyzed to 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1) and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2). V, M1and M2 are antiandrogenic by interacting with the androgen r...

  17. Prenatal Caffeine Exposure Impairs Pregnancy in Rats

    Directory of Open Access Journals (Sweden)

    Maryam Yadegari

    2016-12-01

    Full Text Available Background: In recent years, concerns have been raised about human reproductive disorders. Caffeine consumption is increasing by the world’s population and there is a relationship between caffeine intake and adverse reproductive outcomes. The aim of this study was to evaluate the effects of caffeine on implantation sites, number of live births, birth weight, crown-rump length (CRL and abnormality in pregnant rats. Materials and Methods: In this experimental study, 40 female albino rats (170-190 g were randomly divided into two experimental and two control groups (n=10/each group. In both experimental groups, animals received caffeine intraperitoneally (IP: 150 mg/kg/day on days 1-5 of pregnancy. In experimental group 1, treated animals were euthanized on day 7of pregnancy and the number of implantation sites was counted. In experimental group 2, treated animals maintained pregnant and after delivery, the number of live births, birth weight, CRL and abnormality of neonates were investigated. In control group, animals received IP injections of distilled water. Data were analyzed by independent t test. Results: Results showed that administration of caffeine significantly decreased the number of implantation sites, number of live births and CRL as compared with control group (P<0.05. There were no significant differences regarding birth weight and abnormality of neonate rats between experimental and control groups. Conclusion: These results suggest that caffeine caused anti-fertility effect and significantly decreased CRL in neonate rats.

  18. The rat incisor in toxicologic pathology

    NARCIS (Netherlands)

    Kuijpers, M.H.M.; Kooij, A.J. van de; Slootweg, P.J.

    1996-01-01

    Microscopic examination of the incisors of rats and mice may reveal toxicologically significant changes. First, the incisor morphology reflects the nutritional status of the animal: fluctuations of mineral metabolism and vitamin availability are disclosed by the rodent incisors, because the incisors

  19. Behavioral effects of etiracetam in rats

    NARCIS (Netherlands)

    Wolthuis, O.L.

    1981-01-01

    The effects of etiracetam, a structural analogue or piracetam, were investigated in rats on Y-maze discrimination acquisition, on open field behavior, on one-trial passive avoidance learning and on shuttlebox acquisition and extinction. The results indicate that this drug significantly enhances

  20. Following Exhaustive Exercise in Male Rats

    Directory of Open Access Journals (Sweden)

    reza Badalzadeh

    2014-12-01

    Conclusion: Long-term treatment of rats with cinnamon and regular training improved cardiac hemodynamic through an additive effect. The positive effects of cinnamon and regular training on cardiac function were associated with a reduced serum MDA level and an improved blood lipid profile.

  1. Cytoarchitecture in cultured rat neocortex explants

    NARCIS (Netherlands)

    de Jong, B. M.; Ruijter, J. M.; Romijn, H. J.

    1988-01-01

    Neocortex explants obtained from 6-day-old rat pups and cultured in a serum-free medium from 5 hr to 13 days in vitro (DIV) show preservation of cytoarchitectural characteristics. Major changes in the size of the explants and their layers occur during the first 2 DIV. A radial arrangement of neurons

  2. Swelling of rat hepatocytes stimulates glycogen synthesis

    NARCIS (Netherlands)

    Baquet, A.; Hue, L.; Meijer, A. J.; van Woerkom, G. M.; Plomp, P. J.

    1990-01-01

    In hepatocytes from fasted rats, several amino acids are known to stimulate glycogen synthesis via activation of glycogen synthase. The hypothesis that an increase in cell volume resulting from amino acid uptake may be involved in the stimulation of glycogen synthesis is supported by the following

  3. Disposition of hexobarbital enantiomers in the rat

    NARCIS (Netherlands)

    van der Graaff, M; Vermeulen, N P; Joeres, R P; Breimer, D D

    1983-01-01

    The enantiomers of hexobarbital (HB), designated as (+)-HB and (-)-HB, were administered orally to separate groups of rats. Blood concentration-time curves of the parent compounds and the metabolites 3'-hydroxyhexobarbital (OH-HB) and 3'-ketohexobarbital (K-HB) were determined, as well as the

  4. seed on haematological parameters of albino rats

    African Journals Online (AJOL)

    Dr Ejere

    2015-06-23

    Jun 23, 2015 ... and its indices (haemoglobin content, pack cell volume, mean corpuscular volume, mean corpuscular haemoglobin ... demands in plant-based proteins for humans and livestock, ... hypogea) and animal based proteins (Siddhuraju et al.,. 1995 ..... difference in the packed cell volume (PCV) of albino rats.