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....

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

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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...

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

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.

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

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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

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

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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...

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

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

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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

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

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.

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

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.

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.

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

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

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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.

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

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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.

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

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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.).

[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].

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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.

Dopamine-dependent neurotoxicity of lipopolysaccharide in substantia nigra.

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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.

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

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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

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.

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

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

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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.

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.

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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

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.

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.

Substantia nigra depigmentation and exposure to encephalitis lethargica.

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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.

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

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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.)

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

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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

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

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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

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

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

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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.

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

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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)

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.

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

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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.

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

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

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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.

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

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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.

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

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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)

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

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

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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.

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

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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.)

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.

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

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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.

Intrinsic and integrative properties of substantia nigra pars reticulata neurons

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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

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

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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.

Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

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Zabel Claus

2011-09-01

Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

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

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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.

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.

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.

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

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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)

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

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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.

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

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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

Diagnostic value of combined assessment of olfaction and sustantia nigra hyperechogenicity for Parkinson's disease.

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López Hernández, N; García Escrivá, A; Shalabi Benavent, M

2015-10-01

Hyposmia and substantia nigra hyperechogenicity (SN+) are characteristic markers of Parkinson's disease (PD), although their diagnostic value in isolation may be limited. We evaluated the combined prevalence of both disorders in patients diagnosed with PD and assessed their diagnostic yield compared to a sample with essential tremor (ET) and another group of healthy subjects. Patients diagnosed with PD and ET and treated in our outpatient clinic were enrolled. Olfaction was assessed using the "Sniffin' Sticks" odour identification test (SS-12) and hyperechogenicity of the substantia nigra (SN+) was assessed by transcranial duplex ultrasound. A total of 98 subjects were analysed, comprising 30 with PD, 21 with ET, and 47 controls. The respective prevalence rates of hyposmia (SS-12 .24cm(2)) were 70% and 83.3% in PD, 33.3% and 9.5% in ET, and 17% and 10.6% in controls. Both markers were present in 63% of patients with PD, none of the patients with ET, and only 2 of the controls. Combined use of substantia nigra sonography and olfactory testing with SS-12, two rapid, safe, and accessible tests, was more specific than each isolated marker for distinguishing patients with PD from patients with ET and control subjects. Since both markers have been described in very early phases of PD, combined use may be helpful in providing early diagnosis of PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

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

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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

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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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.

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

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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.

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

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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.

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

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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.

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.

Age-related decline in dopamine transporter in human brain using PET with a new radioligand [18F]FE-PE2I

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Shingai, Yoshitoshi; Tateno, Amane; Arakawa, Ryosuke; Sakayori, Takeshi; Kim, WooChan; Okubo, Yoshiro; Suzuki, Hidenori

2014-01-01

Dopamine transporter (DAT) density is considered as a marker of pre-synaptic function. Numerous neuroimaging studies have consistently demonstrated an age-related decrease in DAT density in normal human brain. However, the precise degree of the regional decline is not yet clear. The purpose of this study was to evaluate the effect of the normal aging process on DAT densities in human-specific brain regions including the substantia nigra and thalamus using positron emission tomography (PET) with [ 18 F]FE-PE2I, a new PET radioligand with high affinity and selectivity for DAT. Thirty-six healthy volunteers ranging in age from 22 to 80 years were scanned with PET employing [ 18 F]FE-PE2I for measuring DAT densities. Region of interest (ROI)-based analysis was used, and ROIs were manually defined for the caudate, putamen, substantia nigra, thalamus, and cerebellar cortex. DAT binding was quantified using a simplified reference tissue model, and the cerebellum was used as reference region. Estimations of binding potential in the caudate, putamen, substantia nigra, and thalamus were individually regressed according to age using simple regression analysis. Estimates of DAT loss per decade were obtained using the values from the regression slopes. There were 7.6, 7.7, and 3.4% per-decade declines in DAT in the caudate, putamen, and substantia nigra, respectively. By contrast, there was no age-related decline of DAT in the thalamus. [ 18 F]FE-PE2I allowed reliable quantification of DAT, not only in the caudate and putamen but also in the substantia nigra. From the results, we demonstrated the age-related decline in the caudate and putamen as reported in previous studies, and additionally for those in the substantia nigra for the first time. (author)

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

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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.)

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

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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

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.)

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

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.

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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.

Brain region-dependent differential expression of alpha-synuclein.

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Taguchi, Katsutoshi; Watanabe, Yoshihisa; Tsujimura, Atsushi; Tanaka, Masaki

2016-04-15

α-Synuclein, the major constituent of Lewy bodies (LBs), is normally expressed in presynapses and is involved in synaptic function. Abnormal intracellular aggregation of α-synuclein is observed as LBs and Lewy neurites in neurodegenerative disorders, such as Parkinson's disease (PD) or dementia with Lewy bodies. Accumulated evidence suggests that abundant intracellular expression of α-synuclein is one of the risk factors for pathological aggregation. Recently, we reported differential expression patterns of α-synuclein between excitatory and inhibitory hippocampal neurons. Here we further investigated the precise expression profile in the adult mouse brain with special reference to vulnerable regions along the progression of idiopathic PD. The results show that α-synuclein was highly expressed in the neuronal cell bodies of some early PD-affected brain regions, such as the olfactory bulb, dorsal motor nucleus of the vagus, and substantia nigra pars compacta. Synaptic expression of α-synuclein was mostly accompanied by expression of vesicular glutamate transporter-1, an excitatory presynaptic marker. In contrast, expression of α-synuclein in the GABAergic inhibitory synapses was different among brain regions. α-Synuclein was clearly expressed in inhibitory synapses in the external plexiform layer of the olfactory bulb, globus pallidus, and substantia nigra pars reticulata, but not in the cerebral cortex, subthalamic nucleus, or thalamus. These results suggest that some neurons in early PD-affected human brain regions express high levels of perikaryal α-synuclein, as happens in the mouse brain. Additionally, synaptic profiles expressing α-synuclein are different in various brain regions. © 2015 Wiley Periodicals, Inc.

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.)

Normal regional brain iron concentration in restless legs syndrome measured by MRI

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Susanne Knake

2009-12-01

Full Text Available Susanne Knake1, Johannes T Heverhagen2, Katja Menzler1, Boris Keil2, Wolfgang H Oertel1, Karin Stiasny-Kolster11Department of Neurology, Center of Nervous Diseases, 2Department of Radiology, Philipps University, Marburg, GermanyAbstract: Using a T2* gradient echo magnetic resonance imaging (MRI sequence, regional T2 signal intensity (SI values, a surrogate marker for T2 values, were determined in 12 regions of interest (substantia nigra, pallidum, caudate head, thalamus, occipital white matter, and frontal white matter bilaterally and in two reference regions (cerebrospinal fluid and bone in 12 patients suffering from moderate to severe idiopathic restless legs syndrome (RLS; mean age 58.5 ± 8.7 years for 12.1 ± 9.1 years and in 12 healthy control subjects (mean age 56.8 ± 10.6 years. Iron deposits shorten T2 relaxation times on T2-weighted MRI. We used regional T2* SI to estimate regional T2-values. A T2-change ratio was calculated for each region of interest relative to the reference regions. We did not find significant differences in any of the investigated brain regions. In addition, serum measures involved in iron metabolism did not correlate with T2 SI values. We could not replicate earlier findings describing reduced regional brain iron concentrations in patients with RLS. Our results do not support the view of substantially impaired regional brain iron in RLS.Keywords: restless legs syndrome, pathophysiology, iron, MRI, substantia nigra

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.

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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.

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

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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.

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

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

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

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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.

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

Enkephalin, dynorphin and substance P in postmortem substantia nigra from normals and schizophrenic patients

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Iadarola, M.J.; Ofri, D.; Kleinman, J.E.

1991-01-01

Three peptide neuromodulators that are found in high concentration in the subtantia nigra: dynorphin A 1,8-met5-enkephalin-arg6-gly7-leu8 and substance P, were measured by specific radioimmunoassays in nigral tissue from normals and schizophrenics postmortem. Substance P and dynorphin were unchanged between the two groups. However, the proenkephalin-derived peptide was significantly elevated in the schizophrenic group. The immunoreactivity was identified as authentic met5-enkephalin-arg6-gly7-leu8 by high pressure liquid chromatography. The data suggest that a different set of regulatory controls exists for nigral enkephalin peptides as compared to dynorphin and substance P, and that the former system may be disordered in schizophrenia

Enkephalin, dynorphin and substance P in postmortem substantia nigra from normals and schizophrenic patients

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Iadarola, M.J.; Ofri, D.; Kleinman, J.E. (National Institute of Dental Research, Bethesda, MD (USA) National Institute of Mental Health, Washington, DC (USA))

1991-01-01

Three peptide neuromodulators that are found in high concentration in the subtantia nigra: dynorphin A 1,8-met5-enkephalin-arg6-gly7-leu8 and substance P, were measured by specific radioimmunoassays in nigral tissue from normals and schizophrenics postmortem. Substance P and dynorphin were unchanged between the two groups. However, the proenkephalin-derived peptide was significantly elevated in the schizophrenic group. The immunoreactivity was identified as authentic met5-enkephalin-arg6-gly7-leu8 by high pressure liquid chromatography. The data suggest that a different set of regulatory controls exists for nigral enkephalin peptides as compared to dynorphin and substance P, and that the former system may be disordered in schizophrenia.

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

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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

Stem Cell Physics. Multiple-Laser-Beam Treatment of Parkinson's Disease

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Stefan, V.

2013-03-01

A novel method for the treatment of Parkinson's disease is proposed. Pluripotent stem cells are laser cultured, using ultrashort wavelength, (around 0.1 micron-ultraviolet radiation-with intensities of a few mW/cm2) , multiple laser beams.[2] The multiple-energy laser photons[3] interact with the neuron DNA molecules to be cloned. The laser created dopaminergic substantia nigra neurons can be, (theoretically), laser transplanted, (a higher focusing precision as compared to a syringe method), into the striatum or substantia nigra regions of the brain, or both. Supported by Nikola Tesla Labs, Stefan University.

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.

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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.

Substantia innominata: MR findings in Parkinson's disease

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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.)

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)

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

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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.

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

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.

Microstructural Changes within the Basal Ganglia Differ between Parkinson Disease Subtypes.

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Nagae, Lidia M; Honce, Justin M; Tanabe, Jody; Shelton, Erika; Sillau, Stefan H; Berman, Brian D

2016-01-01

Diffusion tensor imaging (DTI) of the substantia nigra has shown promise in detecting and quantifying neurodegeneration in Parkinson disease (PD). It remains unknown, however, whether differences in microstructural changes within the basal ganglia underlie PD motor subtypes. We investigated microstructural changes within the basal ganglia of mild to moderately affected PD patients using DTI and sought to determine if microstructural changes differ between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes. Fractional anisotropy, mean diffusivity, radial, and axial diffusivity were obtained from bilateral caudate, putamen, globus pallidus, and substantia nigra of 21 PD patients (12 TD and 9 PIGD) and 20 age-matched healthy controls. T-tests and ANOVA methods were used to compare PD patients, subtypes, and controls, and Spearman correlations tested for relationships between DTI and clinical measures. We found our cohort of PD patients had reduced fractional anisotropy within the substantia nigra and increased mean and radial diffusivity within the substantia nigra and globus pallidus compared to controls, and that changes within those structures were largely driven by the PIGD subtype. Across all PD patients fractional anisotropy within the substantia nigra correlated with disease stage, while in PIGD patients increased diffusivity within the globus pallidus correlated with disease stage and motor severity. We conclude that PIGD patients have more severely affected microstructural changes within the substantia nigra compared to TD, and that microstructural changes within the globus pallidus may be particularly relevant for the manifestation of the PIGD subtype.

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.

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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.

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

Biodistribution study of [I-123] ADAM in mice brain using quantitative autoradiography

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Lin, K.J.; Yen, T.C.; Tzen, K.Y.; Ye, X.X.; Hwang, J.J.; Wey, S.P.; Ting, G.

2002-01-01

Aim: Autoradiography with radioluminography is a delicate method to characterize newly developed radiotracers and to apply them to pharmacological studies. Herein, we reported a biodistribution result of [I-123] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5- iodophenylamine) in mice brain quantitatively using imaging plates. Materials and Methods: 1mCi [I-123] ADAM was injected into male ICR mice through tail veins. Brains were removed at sequential time points ranging from 0.5hr to 4hr after injection. The whole brain was cut into 14mm thick coronal sections using a cyrotome. The sections were thaw-mounted on glass plate and apposed placed on an imaging plate with filter paper standards for 24 hours. Imaging reading was done by a Fuji FLA5000 device. Regions of interest were placed on the globus pallidus, hypothalamus, substantia nigra, raphe nuclei and cerebellum corresponding to the sterotaxic atlas, and the PSL/mm 2 values were measured. The specific binding was expressed as the ratios of (targets - cerebellum) to cerebellum. Results: Autoradiography study of brain showed that the [I-123] ADAM was accumulated at serotonin transporter rich sites, including the olfactory tubercle, globus pallidus, thalamus nuclei, hypothalamus, substantia nigra, interpeduncular nucleus, amygdala and raphe nuclei. Biodistribution of [I-123] ADAM in mice brain using quantitative autoradiography method showed a high specific binding in the substantia nigra and hypothalamus and the time-activity curve peaked at 120 min post-injection. Compatible specific binding result was achieved in the region of hypothalamus as compared with previous study by other group using conventional tissue micro-dissection method (Synapse 38:403-412, 2000). However, higher specific binding was observed in certain small brain regions including substantia nigra, raphe nuclei due to improved spatial resolution of the quantitative autoradiography technique. Conclusion: Our result showed that the

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

The Brainstem Pathologies of Parkinson's Disease and Dementia with Lewy Bodies

NARCIS (Netherlands)

Seidel, Kay; Mahlke, Josefine; Siswanto, Sonny; Krueger, Reijko; Heinsen, Helmut; Auburger, Georg; Bouzrou, Mohamed; Grinberg, Lea T.; Wicht, Helmut; Korf, Horst-Werner; den Dunnen, Wilfred; Rueb, Udo

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are among the human synucleinopathies, which show alpha-synuclein immunoreactive neuronal and/or glial aggregations and progressive neuronal loss in selected brain regions (eg, substantia nigra, ventral tegmental area, pedunculopontine

Conserved microstructure of the Brassica B Genome of Brassica nigra in relation to homologous regions of Arabidopsis thaliana, B. rapa and B. oleracea

Science.gov (United States)

2013-01-01

Background The Brassica B genome is known to carry several important traits, yet there has been limited analyses of its underlying genome structure, especially in comparison to the closely related A and C genomes. A bacterial artificial chromosome (BAC) library of Brassica nigra was developed and screened with 17 genes from a 222 kb region of A. thaliana that had been well characterised in both the Brassica A and C genomes. Results Fingerprinting of 483 apparently non-redundant clones defined physical contigs for the corresponding regions in B. nigra. The target region is duplicated in A. thaliana and six homologous contigs were found in B. nigra resulting from the whole genome triplication event shared by the Brassiceae tribe. BACs representative of each region were sequenced to elucidate the level of microscale rearrangements across the Brassica species divide. Conclusions Although the B genome species separated from the A/C lineage some 6 Mya, comparisons between the three paleopolyploid Brassica genomes revealed extensive conservation of gene content and sequence identity. The level of fractionation or gene loss varied across genomes and genomic regions; however, the greatest loss of genes was observed to be common to all three genomes. One large-scale chromosomal rearrangement differentiated the B genome suggesting such events could contribute to the lack of recombination observed between B genome species and those of the closely related A/C lineage. PMID:23586706

Increased intracranial volume in Parkinson's disease

DEFF Research Database (Denmark)

Krabbe, Katja; Karlsborg, Merete; Hansen, Andreas

2005-01-01

segmentation and outlining of regions in order to identify regional volume changes that might be useful in the diagnosis of the two diseases. RESULTS: Patients with PD had significantly larger intracranial volumes (ICVs) and significantly smaller putaminal and sustantia nigra volumes than controls. MSA...... patients had significantly smaller substantia nigra and caudate volumes than controls but normal intracranial volume. In both patient groups there was a further trend towards smaller amygdala volumes. DISCUSSION: Increased ICV in PD patients is a new finding that may be explained by genetic factors...

Defective functional connectivity between posterior hypothalamus and regions of the diencephalic-mesencephalic junction in chronic cluster headache.

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Ferraro, Stefania; Nigri, Anna; Bruzzone, Maria Grazia; Brivio, Luca; Proietti Cecchini, Alberto; Verri, Mattia; Chiapparini, Luisa; Leone, Massimo

2018-01-01

Objective We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. Methods Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16). Random-effect analyses were performed to study differences between patients and controls in ipsilateral and contralateral-to-the-pain posterior hypothalamus functional connectivity. Results Cluster headache patients showed an increased functional connectivity between the ipsilateral posterior hypothalamus and a number of diencephalic-mesencephalic structures, comprising ventral tegmental area, dorsal nuclei of raphe, and bilateral substantia nigra, sub-thalamic nucleus, and red nucleus ( p cluster headache patients mainly involves structures that are part of (i.e. ventral tegmental area, substantia nigra) or modulate (dorsal nuclei of raphe, sub-thalamic nucleus) the midbrain dopaminergic systems. The midbrain dopaminergic systems could play a role in cluster headache pathophysiology and in particular in the chronicization process. Future studies are needed to better clarify if this finding is specific to cluster headache or if it represents an unspecific response to chronic pain.

Proton MR spectroscopic changes in Parkinson's diseases after thalamotomy

International Nuclear Information System (INIS)

Baik, Hyun-Man; Choe, Bo-Young; Son, Byung-Chul; Jeun, Sin-Soo; Kim, Moon-Chan; Lee, Kwang-Soo; Kim, Bum-Soo; Lee, Jae-Mun; Lee, Hyoung-Koo; Suh, Tae-Suk

2003-01-01

To investigate whether there are significant changes in regional brain metabolism in patients with Parkinson's disease before and after thalamotomy using proton magnetic resonance spectroscopy ( 1 H MRS). Fifteen patients underwent 15 stereotactic thalamotomies for control of medically refractory parkinsonian tremor. Single-voxel 1 H MRS was carried out on a 1.5 T unit using stimulated-echo acquisition mode (STEAM) sequence (TR/TM/TE, 2000/14/20 ms). Spectra were obtained from substantia nigra, thalamus and putamen areas with volumes of interests (7-8 ml) in patients before and after the surgery. Metabolite ratios of NAA/Cho, NAA/Cr and Cho/Cr were calculated from relative peak area measurements. We evaluated alterations of metabolite ratios in brain metabolism in Parkinson's disease patients with clinical outcome following thalamotomy. NAA/Cho ratios showed generally low levels in substantia nigra and thalamus in Parkinson's disease patients with clinical improvement following thalamotomy. In 80% (12/15) patients, decreased NAA/Cho ratios were observed from the selected voxels in substantia nigra after thalamic surgery (P 1 H MRS may be a useful utility for the aid in better understanding the pathophysiologic process in Parkinson's disease patients on the basis of the variation of NAA/Cho ratio

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

Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease

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Milosevic, Luka; Kalia, Suneil K; Hodaie, Mojgan; Lozano, Andres M; Fasano, Alfonso; Popovic, Milos R; Hutchison, William D

2018-01-01

Abstract Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease symptoms. The therapeutic benefits of deep brain stimulation are frequency-dependent, but the underlying physiological mechanisms remain unclear. To advance deep brain stimulation therapy an understanding of fundamental mechanisms is critical. The objectives of this study were to (i) compare the frequency-dependent effects on cell firing in subthalamic nucleus and substantia nigra pars reticulata; (ii) quantify frequency-dependent effects on short-term plasticity in substantia nigra pars reticulata; and (iii) investigate effects of continuous long-train high frequency stimulation (comparable to conventional deep brain stimulation) on synaptic plasticity. Two closely spaced (600 µm) microelectrodes were advanced into the subthalamic nucleus (n = 27) and substantia nigra pars reticulata (n = 14) of 22 patients undergoing deep brain stimulation surgery for Parkinson’s disease. Cell firing and evoked field potentials were recorded with one microelectrode during stimulation trains from the adjacent microelectrode across a range of frequencies (1–100 Hz, 100 µA, 0.3 ms, 50–60 pulses). Subthalamic firing attenuated with ≥20 Hz (P stimulation (silenced at 100 Hz), while substantia nigra pars reticulata decreased with ≥3 Hz (P stimulation. Patients with longer silent periods after 100 Hz stimulation in the subthalamic nucleus tended to have better clinical outcome after deep brain stimulation. At ≥30 Hz the first evoked field potential of the stimulation train in substantia nigra pars reticulata was potentiated (P stimulation (P stimulation-induced inhibition than the substantia nigra pars reticulata likely due to differing ratios of GABA:glutamate terminals on the soma and/or the nature of their GABAergic inputs (pallidal versus striatal). We suggest that enhancement of inhibitory synaptic plasticity, and frequency-dependent potentiation and

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

Study on the relation of brain functional connectivity to movement disorders and cognitive impairment in patients with rapid eye movement sleep behavior disorder

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Hong-ju ZHANG

2017-09-01

Full Text Available Objective To explore the relation between abnormal functional connectivity of substantia nigra and impairment of movement and cognition in patients with rapid eye movement sleep behavior disorder (RBD. Methods A total of 22 subjects, including 14 patients with RBD and 8 sex, age, education-matched healthy controls, were enrolled in this study according to international diagnostic criteria. Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ and Hoehn-Yahr Stage were used to evaluate motor function. Digit Ordering Test - Attention (DOT - A, Symbol Digit Modalities Test (SDMT, Stroop Color-Word Test (SCWT, Trail Making Test (TMT, Rey-Osterrieth Complex Figure Test (ROCFT, Clock Drawing Test (CDT, Boston Naming Test (BNT and Auditory Verbal Learning Test (AVLT were used to evaluate cognitive function. The functional connectivity from left and right substantia nigra to brain region were examined. Results There were no statistical differences of UPDRSⅢ and Hoehn?Yahr Stage between 2 groups (P > 0.05, for all. In comparison with control group, SDMT (P = 0.001, ROCFT-copy (P = 0.013 and AVLT-N2 (P = 0.032 were significantly lower, while TMT-B test was significantly higher (P =0.005 in RBD group. Compared with control group, the functional connectivity of right substantia nigra to left precentral gyrus (P < 0.005 and right angular gyrus (P < 0.005 were all decreased in RBD group. Conclusions The results suggest that cognitive impairment occurs earlier than movement disorders in RBD, and there are abnormal functional connectivity from right substantia nigra to left precentral gyrus and right angular gyrus, proving that abnormal functional connectivity is the base of behavior disorders in RBD. DOI: 10.3969/j.issn.1672-6731.2017.09.005

Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death

OpenAIRE

Zhang, Wei; Zecca, Luigi; Wilson, Belinda; Ren, RW; Wang, Yong-jun; Wang, Xiao-min; Hong, Jau-Shyong

2013-01-01

Substantial evidence indicates that neuroinflammation caused by over-activation of microglial in the substantia nigra is critical in the pathogenesis of dopaminergic neurodegeneration in Parkinson’s disease (PD). Increasing data demonstrates that environmental factors such as rotenone, paraquat play pivotal roles in the death of dopaminergic neurons. Here, potential role and mechanism of neuromelanin (NM), a major endogenous component in dopaminergic neurons of the substantia nigra, on microg...

Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson's disease.

Science.gov (United States)

Scherfler, Christoph; Esterhammer, Regina; Nocker, Michael; Mahlknecht, Philipp; Stockner, Heike; Warwitz, Boris; Spielberger, Sabine; Pinter, Bernadette; Donnemiller, Eveline; Decristoforo, Clemens; Virgolini, Irene; Schocke, Michael; Poewe, Werner; Seppi, Klaus

2013-10-01

Signal abnormalities of the substantia nigra and the olfactory tract detected either by diffusion tensor imaging, including measurements of mean diffusivity, a parameter of brain tissue integrity, and fractional anisotropy, a parameter of neuronal fibre integrity, or transcranial sonography, were recently reported in the early stages of Parkinson's disease. In this study, changes in the nigral and olfactory diffusion tensor signal, as well as nigral echogenicity, were correlated with clinical scales of motor disability, odour function and putaminal dopamine storage capacity measured with 6-[(18)F] fluorolevodopa positron emission tomography in early and advanced stages of Parkinson's disease. Diffusion tensor imaging, transcranial sonography and positron emission tomography were performed on 16 patients with Parkinson's disease (mean disease duration 3.7 ± 3.7 years, Hoehn and Yahr stage 1 to 4) and 14 age-matched healthy control subjects. Odour function was measured by the standardized Sniffin' Sticks Test. Mean putaminal 6-[(18)F] fluorolevodopa influx constant, mean nigral echogenicity, mean diffusivity and fractional anisotropy values of the substantia nigra and the olfactory tract were identified by region of interest analysis. When compared with the healthy control group, the Parkinson's disease group showed significant signal changes in the caudate and putamen by 6-[(18)F] fluorolevodopa positron emission tomography, in the substantia nigra by transcranial sonography, mean diffusivity and fractional anisotropy (P < 0.001, P < 0.01, P < 0.05, respectively) and in the olfactory tract by mean diffusivity (P < 0.05). Regional mean diffusivity values of the substantia nigra and the olfactory tract correlated significantly with putaminal 6-[(18)F] fluorolevodopa uptake (r = -0.52, P < 0.05 and r = -0.71, P < 0.01). Significant correlations were also found between nigral mean diffusivity values and the Unified Parkinson's Disease Rating Scale motor score (r = -0

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

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.

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging

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Lilach Soreq

2017-01-01

Full Text Available Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases.

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

Science.gov (United States)

Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

2017-01-10

Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

HFE Genotype Restricts the Response to Paraquat in a Mouse Model of Neurotoxicity.

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Nixon, Anne M; Meadowcroft, Mark D; Neely, Elizabeth B; Snyder, Amanda M; Purnell, Carson J; Wright, Justin; Lamendella, Regina; Nandar, Wint; Huang, Xuemei; Connor, James R

2018-05-01

Parkinson's disease is marked clinically by motor dysfunction and pathologically by dopaminergic cell loss in the substantia nigra and iron accumulation in the substantia nigra. The driver underlying iron accumulation remains unknown and could be genetic or environmental. The HFE protein is critical for the regulation of cellular iron uptake. Mutations within this protein are associated with increased iron accumulation including in the brain. We have focused on the commonly occurring H63D variant of the HFE gene as a disease modifier in a number of neurodegenerative diseases. To investigate the role of H63D HFE genotype, we generated a mouse model in which the wild-type (WT) HFE gene is replaced by the H67D gene variant (mouse homolog of the human H63D gene variant). Using paraquat toxicity as the model for Parkinson's disease, we found that WT mice responded as expected with significantly greater motor function, loss of tyrosine hydroxylase staining and increase microglial staining in the substantia nigra, and an increase in R 2 relaxation rate within the substantia nigra of the paraquat-treated mice compared to their saline-treated counterparts. In contrast, the H67D mice showed a remarkable resistance to paraquat treatment; specifically differing from the WT mice with no changes in motor function or changes in R 2 relaxation rates following paraquat exposure. At baseline, there were differences between the H67D HFE mice and WT mice in gut microbiome profile and increased L-ferritin staining in the substantia nigra that could account for the resistance to paraquat. Of particular note, the H67D HFE mice regardless of whether or not they were treated with paraquat had significantly less tyrosine hydroxylase immunostaining than WT. Our results clearly demonstrate that the HFE genotype impacts the expression of tyrosine hydroxylase in the substantia nigra, the gut microbiome and the response to paraquat providing additional support that the HFE genotype is a disease

Quantitative Susceptibility Mapping in Parkinson's Disease.

Science.gov (United States)

Langkammer, Christian; Pirpamer, Lukas; Seiler, Stephan; Deistung, Andreas; Schweser, Ferdinand; Franthal, Sebastian; Homayoon, Nina; Katschnig-Winter, Petra; Koegl-Wallner, Mariella; Pendl, Tamara; Stoegerer, Eva Maria; Wenzel, Karoline; Fazekas, Franz; Ropele, Stefan; Reichenbach, Jürgen Rainer; Schmidt, Reinhold; Schwingenschuh, Petra

2016-01-01

Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson's disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson's disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.

The Significance of Brain Transcranial Sonography in Burning Mouth Syndrome: a Pilot Study.

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Zavoreo, Iris; Vučićević, Vanja; Boras; Zadravec, Dijana; Bašić, Vanja; Kes; Ciliga, Dubravka; Gabrić, Dragana

2017-03-01

Burning mouth syndrome (BMS) is a chronic disorder which is affecting mostly postmenopausal women and is characterized by burning symptoms in the oral cavity on the clinically healthy oral mucosa. Also, the results of previous studies suggested a possible role of peripheral and/or central neurological disturbances in these patients. The aim of this study was to analyze patients with burning mouth syndrome using transcranial sonography. By use of transcranial sonography of the brain parenchyma, substantia nigra , midbrain raphe and brain nucleus were evaluated in 20 patients with BMS (64.7±12.3 years) and 20 controls with chronic pain in the lumbosacral region (61.5±15). Statistical analysis was performed by use of Student t test with significance set at pburning mouth syndrome might reflect central disturbances within this syndrome. Burning Mouth Syndrome; Transcranial Sonography; substantia nigra; Midbrain Raphe Nuclei; Red Nucleus.

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.

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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.

Novel Pattern of Iron Deposition in the Fascicula Nigrale in Patients with Parkinson's Disease: A Pilot Study

International Nuclear Information System (INIS)

Peckham, Miriam E.; Dashtipour, Khashayar; Holshouser, Barbara A.; Kani, Camellia; Boscanin, Alex; Kani, Kayvan; Harder, Sheri L.

2016-01-01

Background and Purpose. To determine whether the pattern of iron deposition in the fascicula nigrale in patients with Parkinson's disease would be different from age-matched controls by utilizing quantitative susceptibility mapping to measure susceptibility change. Methods. MRIs of the brain were obtained from 34 subjects, 18 with Parkinson's disease and 16 age- and gender-matched controls. Regions of interest were drawn around the fascicula nigrale and substantia nigra using SWI mapping software by blinded investigators. Statistical analyses were performed to determine susceptibility patterns of both of these regions. Results. Measurements showed significantly increased susceptibility in the substantia nigra in Parkinson's patients and an increased rostral-caudal deposition of iron in the fascicula nigrale in all subjects. This trend was exaggerated with significant correlation noted with increasing age in the Parkinson group. Conclusion. The pattern of an exaggerated iron deposition gradient of the fascicula nigrale in the Parkinson group could represent underlying tract dysfunction. Significant correlation of increasing iron deposition with increasing age may be a cumulative effect, possibly related to disease duration

Identification of four areas each enriched in a unique muscarinic receptor subtype

International Nuclear Information System (INIS)

Hoss, W.; Ellerbrock, B.R.; Goldman, P.S.; Collins, D.A.; Messer, W.S. Jr.

1990-01-01

The affinities of muscarinic agonists and antagonists were determined by autoradiography and image analysis in selected areas of the rat brain. IC 50 values and Hill coefficients for the inhibition of the binding of 0.2 nM [ 3 H]-QNB to dentate gyrus, superior colliculus, rhomboid thalamus and substantia nigra were measured in coronal sections. Pirenzepine displayed a high affinity for receptors in the dentate gyrus and AF-DX 116, the superior colliculus. Both pirenzepine and AF-DX 116 had high affinities for the substantia nigra and low affinities for the rhomboid thalamus. Gallamine displayed a 50-fold preference for superior colliculus over dentate gyrus receptors. Amitriptyline was less selective, showing a modest preference for substantia nigra receptors and 4-DAMP was essentially nonselective. Carbachol was the most selective agonist with a 4000-fold preference for superior colliculus over dentate gyrus receptors. Other agonists except RS 86 were also selective for superior colliculus receptors in the order carbachol >> arecoline > bethanechol > McN A343 = oxotremorine = pilocarpine

Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology.

Science.gov (United States)

Romeo, Stefania; Viaggi, Cristina; Di Camillo, Daniela; Willis, Allison W; Lozzi, Luca; Rocchi, Cristina; Capannolo, Marta; Aloisi, Gabriella; Vaglini, Francesca; Maccarone, Rita; Caleo, Matteo; Missale, Cristina; Racette, Brad A; Corsini, Giovanni U; Maggio, Roberto

2013-01-01

This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague-Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution.

Activation of midbrain structures by associative novelty and the formation of explicit memory in humans.

Science.gov (United States)

Schott, Björn H; Sellner, Daniela B; Lauer, Corinna-J; Habib, Reza; Frey, Julietta U; Guderian, Sebastian; Heinze, Hans-Jochen; Düzel, Emrah

2004-01-01

Recent evidence suggests a close functional relationship between memory formation in the hippocampus and dopaminergic neuromodulation originating in the ventral tegmental area and medial substantia nigra of the midbrain. Here we report midbrain activation in two functional MRI studies of visual memory in healthy young adults. In the first study, participants distinguished between familiar and novel configurations of pairs of items which had been studied together by either learning the location or the identity of the items. In the second study, participants studied words by either rating the words' pleasantness or counting syllables. The ventral tegmental area and medial substantia nigra showed increased activation by associative novelty (first study) and subsequent free recall performance (second study). In both studies, this activation accompanied hippocampal activation, but was unaffected by the study task. Thus midbrain regions seem to participate selectively in hippocampus-dependent processes of associative novelty and explicit memory formation, but appear to be unaffected by other task-relevant aspects.

A Japanese Encephalitis Patient Presenting with Parkinsonism with Corresponding Laterality of Magnetic Resonance and Dopamine Transporter Imaging Findings.

Science.gov (United States)

Tadokoro, Koh; Ohta, Yasuyuki; Sato, Kota; Maeki, Takahiro; Sasaki, Ryo; Takahashi, Yoshiaki; Shang, Jingwei; Takemoto, Mami; Hishikawa, Nozomi; Yamashita, Toru; Lim, Chang Kweng; Tajima, Shigeru; Abe, Koji

2018-03-09

Japanese encephalitis (JE) survivors often present with nigrostriatal aftereffects with parkinsonian features. A 67-year-old woman with JE showed right-dominant clinical parkinsonism and left-dominant substantia nigra lesions after magnetic resonance imaging (MRI). Dopamine transporter (DAT) imaging using 123 I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ( 123 I-FP-CIT) revealed a corresponding left-dominant decrease. The present case is the first to reveal a clear match of laterality between clinical parkinsonism, MRI-based substantia nigra lesions, and impaired DAT in presynaptic dopaminergic neurons in JE.

Hallervorden-Spatz disease: 2 cases of siblings

International Nuclear Information System (INIS)

Song, Jong Gi; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo

1994-01-01

We report two patients with Hallervorden-Spatz disease, who were diagnosed by same MR findings of marked low signal intensity in the globus and substantia nigra. They presented with ataxic and spastic gait, intention tremor, delayed mental development, and dysarthria. They were 7 year-old male and 8 year-old female siblings, who were healthy until 3 years of age when they suffered from progressive symptoms. T2-weighted images showed marked low signal intensity in the globus pallidus and substantia nigra indicating an increased iron deposition, and it might suggest Hallervorden-Spatz disease

Characterization of ["1"1C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain

International Nuclear Information System (INIS)

Yang, Kai-Chun; Stepanov, Vladimir; Amini, Nahid; Martinsson, Stefan; Takano, Akihiro; Halldin, Christer; Nielsen, Jacob; Bundgaard, Christoffer; Bang-Andersen, Benny; Grimwood, Sarah; Farde, Lars; Finnema, Sjoerd J.

2017-01-01

["1"1C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. ["1"1C]Lu AE92686 has high affinity for PDE10A (IC_5_0 = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional ["1"1C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). ["1"1C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume (V_T) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V_T values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V_T values increased by ∝30 % with increasing PET measurement duration from 63 to 123 min, while V_T values in target regions remained stable. Both pretreatment drugs significantly decreased ["1"1C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential (BP_N_D) values, derived with the simplified reference tissue model (SRTM), were 13-17 in putamen and 3-5 in substantia nigra and correlated well to values from the Logan plot analysis. The method proposed for quantification of ["1"1C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that ["1"1C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia nigra. (orig.)

Characterization of [{sup 11}C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain

Energy Technology Data Exchange (ETDEWEB)

Yang, Kai-Chun; Stepanov, Vladimir; Amini, Nahid; Martinsson, Stefan; Takano, Akihiro; Halldin, Christer [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); Nielsen, Jacob [H. Lundbeck A/S, Synaptic Transmission, Valby (Denmark); Bundgaard, Christoffer; Bang-Andersen, Benny [H. Lundbeck A/S, Discovery Chemistry and DMPK, Valby (Denmark); Grimwood, Sarah [Pfizer Inc., Neuroscience and Pain Research Unit, Cambridge, MA (United States); Farde, Lars [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); AstraZeneca PET Science Center at Karolinska Institutet, Personalized Health Care and Biomarkers, Stockholm (Sweden); Finnema, Sjoerd J. [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT (United States)

2017-02-15

[{sup 11}C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [{sup 11}C]Lu AE92686 has high affinity for PDE10A (IC{sub 50} = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional [{sup 11}C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). [{sup 11}C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume (V{sub T}) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V{sub T} values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V{sub T} values increased by ∝30 % with increasing PET measurement duration from 63 to 123 min, while V{sub T} values in target regions remained stable. Both pretreatment drugs significantly decreased [{sup 11}C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential (BP{sub ND}) values, derived with the simplified reference tissue model (SRTM), were 13-17 in putamen and 3-5 in substantia nigra and correlated well to values from the Logan plot analysis. The method proposed for quantification of [{sup 11}C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [{sup 11}C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia

Mycorrhization of containerised Pinus nigra seedlings with Suillus granulatus under open field conditions

Energy Technology Data Exchange (ETDEWEB)

Lazarevic, J.; Keca, N.; Martinovie, A.

2012-07-01

Seedling mycorrhization acts as an efficient tool for improving the quality of seedlings. In this study, the effectiveness of Suillus granulatus, originating from Pinus heldreichii forests (Montenegro), to produce containerized ectomycorrhizal seedlings of autochthonous Pinus nigra in open field conditions was investigated. Spore (106, 107, 108) and vegetative (1:16, 1:8, 1:4) inoculation on ectomycorrhizal formation and seedling growth were tested. Spore and vegetative inoculums of autochthonous Pisolithus arhizus were used in the same trial as additional control treatments. The utilization of vegetative and spore inoculums of autochthonous S. granulatus has proven to be an effective method of obtaining containerized ectomycorrhizal P. nigra seedlings under open field conditions after 11 months. S. granulatus spore inoculations resulted in well developed ectomycorrhiza, decreasing the growth of the P. nigra seedlings in the first growing season. Mycelial inoculations resulted in slightly developed S. granulatus ectomycorrhiza, which increased the growth of the seedlings. Therefore, it would be feasible to use spore inocula of S. granulatus, with 10{sup 6} spores per plant, to produce ectomycorrhizal P. nigra plants on a large scale. Controlled mycorrhizal inoculation of seedlings is not a common practice in Montenegrin and Serbian nurseries; as such, the obtained results will contribute to the enhancement of nursery production of Pinus nigra and other conifers. This also could be assumed as a starting point for many further efforts and investigations with autochthonous fungal and plant material in this region. (Author) 47 refs.

Cell cycle regulation of DNA polymerase beta in rotenone-based Parkinson's disease models.

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Hongcai Wang

Full Text Available In Parkinson's disease (PD, neuronal cells undergo mitotic catastrophe and endoreduplication prior to cell death; however, the regulatory mechanisms remain to be defined. In this study, we investigated cell cycle regulation of DNA polymerase β (poly β in rotenone-based dopaminergic cellular and animal models. Incubation with a low concentration (0.25 µM of rotenone for 1.5 to 7 days resulted in a flattened cell body and decreased DNA replication during S phase, whereas a high concentration (2 µM of rotenone exposure resulted in enlarged, multi-nucleated cells and converted the mitotic cycle into endoreduplication. Consistently, DNA poly β, which is mainly involved in DNA repair synthesis, was upregulated to a high level following exposure to 2 µM rotenone. The abrogation of DNA poly β by siRNA transfection or dideoxycytidine (DDC treatment attenuated the rotenone-induced endoreduplication. The cell cycle was reactivated in cyclin D-expressing dopaminergic neurons from the substantia nigra (SN of rats following stereotactic (ST infusion of rotenone. Increased DNA poly β expression was observed in the substantia nigra pars compacta (SNc and the substantia nigra pars reticulate (SNr of rotenone-treated rats. Collectively, in the in vitro model of rotenone-induced mitotic catastrophe, the overexpression of DNA poly β promotes endoreduplication; in the in vivo model, the upregulation of DNA poly β and cell cycle reentry were also observed in the adult rat substantia nigra. Therefore, the cell cycle regulation of DNA poly β may be involved in the pathological processes of PD, which results in the induction of endoreduplication.

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)

Selective updating of working memory content modulates meso-cortico-striatal activity.

Science.gov (United States)

Murty, Vishnu P; Sambataro, Fabio; Radulescu, Eugenia; Altamura, Mario; Iudicello, Jennifer; Zoltick, Bradley; Weinberger, Daniel R; Goldberg, Terry E; Mattay, Venkata S

2011-08-01

Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling. Published by Elsevier Inc.

Effects of Acute Toluene Toxicity on Different Regions of Rabbit Brain

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Mehmet Demır

2017-01-01

Full Text Available The acute phase effects of toluene on the brain have been investigated in this study using rabbit brain via histopathological, immunohistochemical, and biochemical methods. A total of 20 male rabbits were used as control and experimental groups. Moreover, nerve growth factor (NGF, tumor necrosis factor-alpha (TNF-alpha, dopamine (DA, and glial fibrillary acidic protein (GFAP tests were performed in order to designate the severity of the biochemical damage. In the biochemical evaluation of the prefrontal cortex, hippocampus, hypothalamus, substantia nigra, and entorhinal cortex, the TNF-alpha levels in the brain were found to be significantly higher than in the control group. Levels of dopamine, secreted from the substantia nigra, nerve growth factor (NGF developed from the hippocampal neurons, and GFAP, secreted from astrocyte cells, were detected to be significantly lower in the toluene-administration group than in the control group (p<0.05. In addition, areas of focal vacuolar degeneration (abscess formation, gliosis, and perivascular demyelination, many pyknotic cells and necrosis were observed. In the toluene-administration group compared to the control group, distinct excessive expansions of the blood vessels and severe degeneration in the structure of cells and also dispersed cell borders were observed. Furthermore, abnormal malformations of the nuclei structure of the oligodendrocyte cells were seen. Bodies of the sequential neurons of the hippocampus in the toluene-administration group were distinctly structurally damaged compared to the control group. In addition, cytoplasm of the cortex cell showed serious immune reactivity in the experimental group.

Tolerance of Brassica nigra to Pieris brassicae herbivory

NARCIS (Netherlands)

Blatt, S.E.; Smallegange, R.C.; Hess, L.; Harvey, J.A.; Dicke, M.; Loon, van J.J.A.

2008-01-01

Black mustard, Brassica nigra (L.) Koch, is a wild annual species found throughout Europe and fed on by larvae of the large cabbage-white butterfly, Pieris brassicae L. We examined the impact of herbivory from P. brassicae, a gregarious herbivore, on B. nigra grown from wild seed collected locally.

Tolerence of Braccica nigra to Pieris brassicae herbivory

NARCIS (Netherlands)

Blatt, S.E.; Smallegange, R.C.; Hess, L.; Harvey, J.A.; Dicke, D.; van Loon, J.J.A.

2008-01-01

Black mustard, Brassica nigra (L.) Koch, is a wild annual species found throughout Europe and fed on by larvae of the large cabbage-white butterfly, Pieris brassicae L. We examined the impact of herbivory from P. brassicae, a gregarious herbivore, on B. nigra grown from wild seed collected locally.

Creatine supplementation and exercise as possible therapeutic treatments in Parkinson’s Disease: A review

OpenAIRE

Graham, S. M..; Baird, M..; Boyd, G. W..

2014-01-01

Parkinson’s disease (PD) is the second most common progressive neurodegenerative condition after Alzheimer’s Disease. It is characterized by a progressive loss of dopaminergic neurons inthe substantia nigra region of the brain. Symptoms and signs manifest as motor disorders affecting balance and physical capacity, and non-motor symptoms such as cognitive decline and mood disorders. People with PD face considerable difficulties coping with associated physical and psychological changes that aff...

The role of melatonin on brain iron homeostasis and its relation to Parkinson’s Disease

OpenAIRE

Lai, Hien Tet

2017-01-01

Parkinson’s Disease (PD) is the second most common neurological disorder after Alzheimer’s Disease. The disease will manifest with the loss of up to 70% of the dopaminergic neurons in the Substantia Nigra (SN) region and it mainly affects the elderly. One of the common pathological hallmarks for PD is the excessive iron accumulation within the SN region of the brain. However, the pathogenesis for of the excessive iron levels accumulation in the SN is unclear. The increase in intracellular oxi...

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

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.

Brain monoamine oxidase B and A in human parkinsonian dopamine deficiency disorders.

Science.gov (United States)

Tong, Junchao; Rathitharan, Gausiha; Meyer, Jeffrey H; Furukawa, Yoshiaki; Ang, Lee-Cyn; Boileau, Isabelle; Guttman, Mark; Hornykiewicz, Oleh; Kish, Stephen J

2017-09-01

See Jellinger (doi:10.1093/awx190) for a scientific commentary on this article. The enzyme monoamine oxidases (B and A subtypes, encoded by MAOB and MAOA, respectively) are drug targets in the treatment of Parkinson's disease. Inhibitors of MAOB are used clinically in Parkinson's disease for symptomatic purposes whereas the potential disease-modifying effect of monoamine oxidase inhibitors is debated. As astroglial cells express high levels of MAOB, the enzyme has been proposed as a brain imaging marker of astrogliosis, a cellular process possibly involved in Parkinson's disease pathogenesis as elevation of MAOB in astrocytes might be harmful. Since brain monoamine oxidase status in Parkinson's disease is uncertain, our objective was to measure, by quantitative immunoblotting in autopsied brain homogenates, protein levels of both monoamine oxidases in three different degenerative parkinsonian disorders: Parkinson's disease (n = 11), multiple system atrophy (n = 11), and progressive supranuclear palsy (n = 16) and in matched controls (n = 16). We hypothesized that if MAOB is 'substantially' localized to astroglial cells, MAOB levels should be generally associated with standard astroglial protein measures (e.g. glial fibrillary acidic protein). MAOB levels were increased in degenerating putamen (+83%) and substantia nigra (+10%, non-significant) in multiple system atrophy; in caudate (+26%), putamen (+27%), frontal cortex (+31%) and substantia nigra (+23%) of progressive supranuclear palsy; and in frontal cortex (+33%), but not in substantia nigra of Parkinson's disease, a region we previously reported no increase in astrocyte protein markers. Although the magnitude of MAOB increase was less than those of standard astrocytic markers, significant positive correlations were observed amongst the astrocyte proteins and MAOB. Despite suggestions that MAOA (versus MAOB) is primarily responsible for metabolism of dopamine in dopamine neurons, there was no loss of the

Autoradiographic localization of substance P receptors using 125I substance P

International Nuclear Information System (INIS)

Shults, C.W.; Quirion, R.; Jensen, R.T.; Moody, T.W.; O'Donohue, T.L.; Chase, T.N.

1982-01-01

This paper describes a method for localization of substance P receptors in the rat central nervous system using 125 I labeled substance P in an autoradiographic procedure. Particularly high densities of substance P receptors were observed in the olfactory bulb, dentate gyrus, amygdala, superior colliculus, and locus coeruleus. Surprisingly low densities of substance P receptors were found in the substantia nigra pars reticulata, a region which contains high concentrations of substance P

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

Trinucleotide repeat microsatellite markers for Black Poplar (Populus nigra L.)

NARCIS (Netherlands)

Smulders, M.J.M.; Schoot, van der J.; Arens, P.; Vosman, B.

2001-01-01

Using an enrichment procedure, we have cloned microsatellite repeats from black poplar (Populus nigra L.) and developed primers for microsatellite marker analysis. Ten primer pairs, mostly for trinucleotide repeats, produced polymorphic fragments in P. nigra. Some of them also showed amplification

The Significance of Brain Transcranial Sonography in Burning Mouth Syndrome: a Pilot Study

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Iris Zavoreo

2017-01-01

Full Text Available Objective: Burning mouth syndrome (BMS is a chronic disorder which is affecting mostly postmenopausal women and is characterized by burning symptoms in the oral cavity on the clinically healthy oral mucosa. The results of previous studies suggested a possible role of peripheral and/or central neurological disturbances in these patients. The aim of this study was to analyze patients with burning mouth syndrome using transcranial sonography. Methods: By use of transcranial sonography of the brain parenchyma, substantia nigra, midbrain raphe and brain nucleus were evaluated in 20 patients with BMS (64.7±12.3 years and 20 controls with chronic pain in the lumbosacral region (61.5±15. Statistical analysis was performed by use of Student t test with significance set at p<0.05. Results: The results of this study have shown hypoechogenicity of the substantia nigra and midbrain raphe as well as hyperechogenicity of the brain nucleus in BMS patients (p<0,05 as compared to controls. Conclusions: Altered transcranial sonography findings of the brain parenchyma, midbrain raphe and brain nucleus in patients with burning mouth syndrome might reflect central disturbances within this syndrome.

Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia

International Nuclear Information System (INIS)

Palacios, J.M.; Chinaglia, G.; Rigo, M.; Ulrich, J.; Probst, A.

1991-01-01

Autoradiographic techniques were used to examine the distribution and levels of neurotensin receptor binding sites in the basal ganglia and related regions of the human brain. Monoiodo ( 125 I-Tyr3)neurotensin was used as a ligand. High amounts of neurotensin receptor binding sites were found in the substantia nigra pars compacta. Lower but significant quantities of neurotensin receptor binding sites characterized the caudate, putamen, and nucleus accumbens, while very low quantities were seen in both medial and lateral segments of the globus pallidus. In Huntington's chorea, the levels of neurotensin receptor binding sites were found to be comparable to those of control cases. Only slight but not statistically significant decreases in amounts of receptor binding sites were detected in the dorsal part of the head and in the body of caudate nucleus. No alterations in the levels of neurotensin receptor binding sites were observed in the substantia nigra pars compacta and reticulata. These results suggest that a large proportion of neurotensin receptor binding sites in the basal ganglia are located on intrinsic neurons and on extrinsic afferent fibers that do not degenerate in Huntington's disease

Separate groups of dopamine neurons innervate caudate head and tail encoding flexible and stable value memories

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Hyoung F Kim

2014-10-01

Full Text Available Dopamine neurons are thought to be critical for reward value-based learning by modifying synaptic transmissions in the striatum. Yet, different regions of the striatum seem to guide different kinds of learning. Do dopamine neurons contribute to the regional differences of the striatum in learning? As a first step to answer this question, we examined whether the head and tail of the caudate nucleus of the monkey (Macaca mulatta receive inputs from the same or different dopamine neurons. We chose these caudate regions because we previously showed that caudate head neurons learn values of visual objects quickly and flexibly, whereas caudate tail neurons learn object values slowly but retain them stably. Here we confirmed the functional difference by recording single neuronal activity while the monkey performed the flexible and stable value tasks, and then injected retrograde tracers in the functional domains of caudate head and tail. The projecting dopaminergic neurons were identified using tyrosine hydroxylase immunohistochemistry. We found that two groups of dopamine neurons in the substantia nigra pars compacta project largely separately to the caudate head and tail. These groups of dopamine neurons were mostly separated topographically: head-projecting neurons were located in the rostral-ventral-medial region, while tail-projecting neurons were located in the caudal-dorsal-lateral regions of the substantia nigra. Furthermore, they showed different morphological features: tail-projecting neurons were larger and less circular than head-projecting neurons. Our data raise the possibility that different groups of dopamine neurons selectively guide learning of flexible (short-term and stable (long-term memories of object values.

http://www.bio.uaic.ro/publicatii/anale_biochimie/data/archive/papers/2007/2/2007_Anale_GBM_VIII_f2_l23.pdf

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Lucian Hritcu

2007-12-01

Full Text Available The effects of lesioning the ventral tegmental area or substantia nigra pars reticulata by means of bilateral microinjections of two doses of kainic acid (50 ng/250 nl and 100 ng/500 nl were investigated to clarify the role of the mesotelencephalic dopamine system in learning and memory processes. Our findings suggest that ventral tegmental area and substantia nigra dopaminergic neurons play an important role in retention of both short-term memory, tested in the Ymaze task and long-term memory evaluated with the multi-trial passive avoidance test, without affecting memory acquisition. As compared to short-term memory, long-term memory is more susceptible to the decreased dopamine level in nervous structures involved in processing and storage of information

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

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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.

Differences in regional grey matter volumes in currently ill patients with anorexia nervosa.

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Phillipou, Andrea; Rossell, Susan Lee; Gurvich, Caroline; Castle, David Jonathan; Abel, Larry Allen; Nibbs, Richard Grant; Hughes, Matthew Edward

2018-01-01

Neurobiological findings in anorexia nervosa (AN) are inconsistent, including differences in regional grey matter volumes. Methodological limitations often contribute to the inconsistencies reported. The aim of this study was to improve on these methodologies by utilising voxel-based morphometry (VBM) analysis with the use of diffeomorphic anatomic registration through an exponentiated lie algebra algorithm (DARTEL), in a relatively large group of individuals with AN. Twenty-six individuals with AN and 27 healthy controls underwent a T1-weighted magnetic resonance imaging (MRI) scan. AN participants were found to have reduced grey matter volumes in a number of areas including regions of the basal ganglia (including the ventral striatum), and parietal and temporal cortices. Body mass index (BMI) and global scores on the Eating Disorder Examination Questionnaire (EDE-Q) were also found to correlate with grey matter volumes in a region of the brainstem (including the substantia nigra and ventral tegmental area) in AN, and predicted 56% of the variance in grey matter volumes in this area. The brain regions associated with grey matter reductions in AN are consistent with regions responsible for cognitive deficits associated with the illness including anhedonia, deficits in affect perception and saccadic eye movement abnormalities. Overall, the findings suggest reduced grey matter volumes in AN that are associated with eating disorder symptomatology. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Multimodal MRI Evaluation of the MitoPark Mouse Model of Parkinson's Disease.

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Linlin Cong

Full Text Available The MitoPark mouse, a relatively new genetic model of Parkinson's disease (PD, has a dopaminergic neuron-specific knock-out that inactivates the mitochondrial transcription factor A (Tfam, a protein essential for mitochondrial DNA expression and maintenance. This study used multimodal MRI to characterize the neuroanatomical correlates of PD-related deficits in MitoPark mice, along with functional behavioral tests. Compared with age-matched wild-type animals, MitoPark mice at 30 weeks showed: i reduced whole-brain volume and increased ventricular volume, indicative of brain atrophy, ii reduced transverse relaxation time (T2* of the substantia nigra and striatum, suggestive of abnormal iron accumulation, iii reduced apparent diffusion coefficient in the substantia nigra, suggestive of neuronal loss, iv reduced fractional anisotropy in the corpus callosum and substantia nigra, indicative of white-matter damages, v cerebral blood flow was not significantly affected, and vi reduced motor activity in open-field tests, reduced memory in novel object recognition tests, as well as decreased mobility in tail suspension tests, an indication of depression. In sum, MitoPark mice recapitulate changes in many MRI parameters reported in PD patients. Multimodal MRI may prove useful for evaluating neuroanatomical correlates of PD pathophysiology in MitoPark mice, and for longitudinally monitoring disease progression and therapeutic interventions for PD.

Tyrosine Hydroxylase (TH)- and Aromatic-L-Amino Acid Decarboxylase (AADC)-Immunoreactive Neurons of the Common Marmoset (Callithrix jacchus) Brain: An Immunohistochemical Analysis

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Karasawa, Nobuyuki; Hayashi, Motoharu; Yamada, Keiki; Nagatsu, Ikuko; Iwasa, Mineo; Takeuchi, Terumi; Uematsu, Mitsutoshi; Watanabe, Kazuko; Onozuka, Minoru

2007-01-01

From the perspective of comparative morphology, the distribution of non-monoaminergic neurons in the common marmoset (Callithrix jacchus) was investigated using an immunohistochemical method with specific antibodies to tyrosine hydroxylase (TH) and aromatic-L-amino acid decarboxylase (AADC). TH-immunoreactive (IR) neurons (but not AADC-IR) neurons were observed in the olfactory tubercle, preoptic suprachiasmatic nucleus, periventricular hypothalamic nucleus, arcuate nucleus, paraventricular nucleus, periaqueductal gray matter, medial longitudinal fasciculus, substantia nigra, and nucleus solitaris. In contrast, AADC-IR (but not TH-IR), small, oval and spindle-shaped neurons were sparsely distributed in the following areas: the hypothalamus from the anterior nucleus to the lateral nucleus, the dorsomedial nucleus, the dorsomedial area of the medial mammillary nucleus and the arcuate nucleus; the midbrain, including the stria medullaris and substantia nigra; and the medulla oblongata, including the dorsal area of the nucleus solitaris and the medullary reticular nucleus. The distribution of AADC-IR neurons was not as extensive in the marmoset as it is in rats. However, these neurons were located in the marmoset, but not the rat substantia nigra. Furthermore, AADC-IR neurons that are present in the human striatum were absent in that of the marmoset. The present results indicate that the distribution of non-monoaminergic neurons in the brain of the common marmoset is unique and different from that in humans and rodents. PMID:17653300

First Record of Dicheilonema Ciconiae (Nematoda, Diplotriaenoidea From Ciconia Nigra (Aves, Ciconiidae in Ukraine

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Syrota Ya. Yu.

2016-08-01

Full Text Available Five specimens of a parasitic nematode Dicheilonema ciconiae (Schrank, 1788 were collected from black stork, Ciconia nigra Linnaeus, in Kyiv Zoological Park. Identification of the nematodes was confirmed by morphological examination of the specimens collected. The ornamentation of the body cuticle in caudal region of males (area rugosa is first described in D. ciconiae.

Iron as a risk factor in neurological diseases

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Galazka-Friedman, Jolanta

2008-02-01

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson’s and Alzheimer’s disease, and progressive supranuclear palsy. Our own studies with the use of Mössbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer’s disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson’s disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

Iron as a risk factor in neurological diseases

International Nuclear Information System (INIS)

Galazka-Friedman, Jolanta

2008-01-01

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson's and Alzheimer's disease, and progressive supranuclear palsy. Our own studies with the use of Moessbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer's disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson's disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

Evaluation of phenolic compounds and lipid-lowering effect of Morus nigra leaves extract

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ANA LÚCIA B. ZENI

2017-12-01

Full Text Available ABSTRACT Morus nigra L. (Moraceae is a tree known as black mulberry and the leaves are used in folk medicine in the treatment of diabetes, high cholesterol and menopause symptoms. The aim of this study was to evaluate the M. nigra leaves phytochemical profile in different extractions and the hypolipidemic effect of the infusion comparing to the fenofibrate. Morus nigra infusion (MN showed higher amounts of phenolics and flavonoids (83.85 mg/g and 79.96 µg/g, respectively, as well as antioxidant activity (83.85% than decoction or hydromethanolic extracts. Although, decoction showed the best result for ascorbic acid (4.35 mg/100 g than hydromethanolic or infusion (2.51 or 2.13 mg/100 g, respectively. The phenolic acids gallic, chlorogenic and caffeic and the flavonoids quercetin, rutin and catechin were found in the M. nigra extracts. Hyperlipidemic rats treated with 100, 200 or 400 mg/kg of MN decreased serum cholesterol, triglycerides and normalized lipoproteins. Furthermore, MN inhibited lipid peroxidation in liver, kidney and brain of hyperlipidemic rats. This study provides evidence that M. nigra leaves extracts are rich in polyphenols, mainly chlorogenic acid, which normalized hyperlipidemic disturbance. The results suggest a potential therapeutic effect of the M. nigra leaves infusion on dislipidemic condition and related oxidative stress.

Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations

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2015-01-01

In vivo monitoring of dopamine via microdialysis has demonstrated that acute, systemic ethanol increases extracellular dopamine in regions innervated by dopaminergic neurons originating in the ventral tegmental area and substantia nigra. Simultaneous measurement of dialysate dopamine and ethanol allows comparison of the time courses of their extracellular concentrations. Early studies demonstrated dissociations between the time courses of brain ethanol concentrations and dopaminergic responses in the nucleus accumbens (NAc) elicited by acute ethanol administration. Both brain ethanol and extracellular dopamine levels peak during the first 5 min following systemic ethanol administration, but the dopamine response returns to baseline while brain ethanol concentrations remain elevated. Post hoc analyses examined ratios of the dopamine response (represented as a percent above baseline) to tissue concentrations of ethanol at different time points within the first 25–30 min in the prefrontal cortex, NAc core and shell, and dorsomedial striatum following a single intravenous infusion of ethanol (1 g/kg). The temporal patterns of these “response ratios” differed across brain regions, possibly due to regional differences in the mechanisms underlying the decline of the dopamine signal associated with acute intravenous ethanol administration and/or to the differential effects of acute ethanol on the properties of subpopulations of midbrain dopamine neurons. This Review draws on neurochemical, physiological, and molecular studies to summarize the effects of acute ethanol administration on dopamine activity in the prefrontal cortex and striatal regions, to explore the potential reasons for the regional differences observed in the decline of ethanol-induced dopamine signals, and to suggest directions for future research. PMID:25537116

Early Life Stress, Depression And Parkinson's Disease: A New Approach.

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Dallé, Ernest; Mabandla, Musa V

2018-03-19

This review aims to shed light on the relationship that involves exposure to early life stress, depression and Parkinson's disease (PD). A systematic literature search was conducted in Pubmed, MEDLINE, EBSCOHost and Google Scholar and relevant data were submitted to a meta-analysis . Early life stress may contribute to the development of depression and patients with depression are at risk of developing PD later in life. Depression is a common non-motor symptom preceding motor symptoms in PD. Stimulation of regions contiguous to the substantia nigra as well as dopamine (DA) agonists have been shown to be able to attenuate depression. Therefore, since PD causes depletion of dopaminergic neurons in the substantia nigra, depression, rather than being just a simple mood disorder, may be part of the pathophysiological process that leads to PD. It is plausible that the mesocortical and mesolimbic dopaminergic pathways that mediate mood, emotion, and/or cognitive function may also play a key role in depression associated with PD. Here, we propose that a medication designed to address a deficiency in serotonin is more likely to influence motor symptoms of PD associated with depression. This review highlights the effects of an antidepressant, Fluvoxamine maleate, in an animal model that combines depressive-like symptoms and Parkinsonism.

Effects of aging on nitrergic system in human basal nuclei

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Bruno Lopes dos Santos

2014-10-01

Full Text Available Nitric oxide (NO is a gaseous molecule that plays a role in a number of physiologic processes. The available evidence suggests that NO is a major neurotransmitter involved in motor control and emotion/behavior modulation. To investigate the distribution and morphology of the nitrergic system in human basal nuclei, we studied samples from the striatum, globus pallidus, subthalamic nucleus, substantia nigra and pedunculopontine nucleus of 20 human brains from subjects without neurologic/psychiatric diseases. The samples were stained for NADPH-diaphorase using histochemistry and for neuronal NO synthase using immunohistochemistry. We then analyzed the nitrergic neuronal density and its morphometric parameters. Our data demonstrated that: (I the most posterior regions of the striatum exhibit a higher neuronal density; (II the limbic cortex-associated areas of the striatum exhibit higher neuronal density than other functional subdivisions; (III approximately 90% of the neurons in the subthalamic nucleus express NO; (IV the pedunculopontine nucleus exhibits a massive nitrergic neuronal density; (V in the globus pallidus, there is a marked presence of NO neurons in the medial medullary lamina; and (VI nitrergic neurons were not detected in the substantia nigra. Aging did not change the neuronal density or the morphometric parameters of nitrergic neurons in the analyzed nuclei.

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

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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

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

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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.

Hepatoprotective activity of aqueous methanolic extract of Morus nigra against paracetamol-induced hepatotoxicity in mice

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Tauqeer Hussain Mallhi

2014-03-01

Full Text Available Morus nigra (Family Moraceae is traditionally used injaundice, diabetes, hypertension, cough, fever and cancer. The current study was conducted to determine hepatoprotective activity of aqueous methanolic extract of leaves of M. nigra. Two doses of 250 mg/kg p.o and 500 mg/kg p.o showed that extract of M. nigra produced significant (p<0.001 reduction in liver enzymes (ALT, AST, ALP and total bilirubin induced by paracetamol and the results are comparable to silymarin (p<0.001. Results were supported by histopathologi-cal investigations, phytochemical screening and detection of active consti-tuents by HPLC. The current study showed that aqueous methanolic extract of M. nigra possess hepatoprotective activity that might be due to quercetin, luteolin and isorhamnetin. It was concluded from this study that M. nigra has hepatoprotective activity against paracetamol induced liver injury in mice.

Dalnigrin, a neoflavonoid marker for the identification of Brazilian rosewood (Dalbergia nigra) in CITES enforcement.

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Kite, Geoffrey C; Green, Paul W C; Veitch, Nigel C; Groves, Madeleine C; Gasson, Peter E; Simmonds, Monique S J

2010-07-01

International trade in Brazilian rosewood, Dalbergia nigra (Vell.) Allemão ex Benth., is regulated by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). One problem in enforcing these regulations is the difficulty in distinguishing the wood of D. nigra from that of a closely-related but unregulated species, Dalbergia spruceana Benth. Using LC-MS to analyse methanol extracts of xylaria specimens, we identified a chemical marker for D. nigra heartwood, and determined its structure as the neoflavonoid 6-hydroxy-7-methoxy-4-(4-methoxyphenyl)-2H-1-benzopyran-2-one (4'-O-methylmelanettin; dalnigrin), using spectroscopic techniques. Dalnigrin was present in all nine available heartwood specimens of D. nigra, but it was not detected in extracts of 59 other heartwood samples representing 15 species of Dalbergia, including D. spruceana. Five other phenolic compounds were also isolated from D. nigra heartwood and similarly identified as the neoflavonoids 3'-hydroxymelanettin, melanettin, melannein and dalbergin, and the isoflavone caviunin. In extracts of D. spruceana heartwood, pseudobaptigenin was identified by LC-MS to be a major phenolic component that was not detected in wood extracts of D. nigra. We conclude that chemical analysis, in combination with anatomical investigation, can provide persuasive evidence to support the positive identification of untreated heartwood of D. nigra. 2010 Elsevier Ltd. All rights reserved.

Efferent connections and nigral afferents of the nucleus accumbens septi in the rat

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Nauta, W J.H.; Smith, G P; Faull, R L.M.; Domesick, V B [Massachusetts Inst. of Tech., Cambridge (USA). Dept. of Psychology

1978-01-01

The results of this study by the methods of autoradiographic fiber-tracing and retrograde cell-labelling confirm earlier reports of accumbens projections to the globus pallidus and to dorsal strata of the medial half of the substantia nigra. Also in accord with previous autoradiographic evidence, sparser projections could be traced to a variety of subcortical structures implicated in the circuitry of the limbic system: bed nucleus of the stria terminalis, septum, preoptic region, hypothalamus, ventral tegmental area, nuclei paratenialis and mediodorsalis thalami, and lateral habenular nucleus. Contrary to earlier reports, striatopallidal fibers from the accumbens were found to be distributed largely to the subcommissural part of the external pallidal segment and to avoid almost entirely the internal pallidal segment. Mesencephalic projections from the accumbens largely coincide with those from the preoptic region and hypothalamus; like the latter they prominantly involve the region of the out-lying nigral cell groups A10 and A8 and extend caudally beyond the nigral complex to the cuneiform and parabrachial regions of the tegmentum as well as to caudoventral parts of the central grey substance. Horseradish peroxidase injected into the nucleus accumbens labels numerous neurons in the region of cell group A10 and in the supralemniscal 'retrorubral nucleus', but only sporadic cells in the pars compacta of the substantia nigra proper. It thus appears that the accumbens projects to a region of the nigral complex considerably larger than that from which it receives nigrostriatal fibers, and hence, that the nigro-striato-nigral circuit associated with the accumbens is not organized in a mode of simple point-for-point reciprocity. The problem of delimiting the accumbens from the rest of the striatum is examined by comparing cases of tracer injection into various discrete loci within the ventral zone of the striatum.

Neuroprotection in Parkinson's disease: modafinil and Δ9-tetrahydrocannabinol

NARCIS (Netherlands)

Vliet, S.A.M. van

2007-01-01

In Parkinson's disease (PD) is the output of the basal ganglia irreversibly affected due to degeneration of the neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta. This results in manifestation of symptoms including akinesia, postural instability, rigidity and resting

The Pitx3-deficient aphakia mouse: a naturally occurring mouse model of dopamine deficiency

NARCIS (Netherlands)

van den Munckhof, P.

2011-01-01

De neurotransmitter dopamine (DA) is betrokken bij hersenfuncties als beweging, cognitie en emotioneel- en beloningsgerelateerd gedrag. Het afsterven van DA-neuronen in de substantia nigra in de hersenen veroorzaakt de ziekte van Parkinson. DA-stoornissen in andere hersengebieden worden in verband

Anti-Inflammatory Modulation of Microglia via CD163-Targeted Glucocorticoids Protects Dopaminergic Neurons in the 6-OHDA Parkinson's Disease Model

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Tentillier, Noemie; Etzerodt, Anders; Olesen, Mads N

2016-01-01

intravenous CD163-targeted liposomes with Dexa for 3 weeks exhibited better motor performance than the control groups and had minimal glucocorticoid-driven side effects. Furthermore, these animals showed better survival of dopaminergic neurons in substantia nigra and an increased number of microglia...

Evaluation of new treatment strategies for Parkinson's disease in animal models : the therapeutic efficacy of the dopamine D1 antagonist SKF 83959 and the neuroprotective agent CGP 3466B

NARCIS (Netherlands)

Andringa, Gerda

2000-01-01

Parkinson's disease is a progressive neurodegenerative disorder, characterized by a loss of dopamine neurons in the substantia nigra pars compacta. The current medical treatments for patients with this disease have two major disadvantages: they induce severe response complications on the longer term

The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts

NARCIS (Netherlands)

Gosso, M.F.; de Geus, E.J.C.; van Belzen, MJ; Polderman, T.J.C.; Heutink, P.; Boomsma, D.I.; Posthuma, D.

2006-01-01

The synaptosomal-associated protein of 25 kDa (SNAP-25) gene plays an integral role in synaptic transmission, and is differentially expressed in the mammalian brain in the neocortex, hippocampus, anterior thalamic nuclei, substantia nigra and cerebellar granular cells. Recent studies have suggested

Screening of Toll-like receptors expression in multiple system atrophy brains

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Brudek, Tomasz; Winge, Kristian; Agander, Tina Klitmøller

2013-01-01

The family of Toll-like receptors (TLRs) plays a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules. It was recently suggested that TLRs have an important role in the crosstalk between neurons and glial cells in the central nervous system, thus...... inclusions in oligodendrocytes. α-Synuclein can act as a danger-associated molecular pattern and alter TLR expression thereby activating inflammatory responses in the brain. In this study, using real-time PCR, we assessed the expression of TLRs (TLR1-10) in selected areas of MSA brains (substantia nigra......TLR-1 mRNA were elevated in substantia nigra and striatum whereas levels of hTLR-8 and hTLR-9 mRNAs were significantly higher in cerebella from MSA patients. The concerted alteration of expression of multiple TLRs in MSA brains can be of relevance for understanding the pathogenesis of the disease....

Presence of proNGF-Sortilin Signaling Complex in Nigral Dopamine Neurons and Its Variation in Relation to Aging, Lactacystin and 6-OHDA Insults

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Ken Kam-Lin Yung

2013-07-01

Full Text Available Growing evidence has shown that proNGF-p75NTR-sortilin signaling might be a crucial factor in neurodegeneration, but it remains unclear if it may function in nigral neurons under aging and disease. The purpose of this study is to examine and quantify proNGF and sortilin expression in the substantia nigra and dynamic changes of aging in lactacystin and 6-hydroxydopamine (6-OHDA rat models of Parkinson’s disease using immunofluorescence, electronic microscopy, western blot and FLIVO staining methods. The expression of proNGF and sortilin was abundantly and selectively identified in tyrosine hydroxylase (TH-containing dopamine neurons in the substantia nigra. These proNGF/TH, sortilin/TH-positive neurons were densely distributed in the ventral tier, while they were less distributed in the dorsal tier, where calbindin-D28K-containing neurons were numerously located. A correlated decrease of proNGF, sortilin and TH was also detected during animal aging process. While increase of proNGF, sortilin and cleaved (active caspase-3 expression was found in the lactacystin model, dynamic proNGF and sortilin changes along with dopamine neuronal loss were demonstrated in the substantia nigra of both the lactacystin and 6-OHDA models. This study has thus revealed the presence of the proNGF-sortilin signaling complex in nigral dopamine neurons and its response to aging, lactacystin and 6-OHDA insults, suggesting that it might contribute to neuronal apoptosis or neurodegeneration during pathogenesis and disease progression of Parkinson’s disease; the underlying mechanism and key signaling pathways involved warrant further investigation.

Variation of leaf margin serration in Populus nigra of industrial dumps

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Yu. A. Shtirs

2017-07-01

Full Text Available The variability of leaf margin serration of Populus nigra L. in conditions of industrial dumps (coal mines dumps and overburden dumps and city park is estimated. The value of this indicator is in the range from 1.25 to 1.76 and significantly increases along the gradient: coal mines dumps – overburden dumps – city park. From the number of selected gradations of P. nigra leaf blades, the gradation with values of 1.45-1.55 is most pronounced according to the analyzed index for industrial dumps, for the park – with the values of 1.55-1.65. The degree of serration of edge leaf blade is characterized by low values of variation – coefficient of variation is less than 10.0%. We registered the significant positive correlation between the average values of leaf margin serration and the length of P. nigra leaf blade.

Enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity: selective radioassay, properties, and regional distribution in human brain

International Nuclear Information System (INIS)

Llorens, C.; Malfroy, B.; Schwartz, J.C.; Gacel, G.; Roques, B.P.; Roy, J.; Morgat, J.L.; Javoy-Agid, F.; Agid, Y.

1982-01-01

The compound [ 3 H-Tyr 1 ,D-Ala 2 ,Leu-OH 5 ]enkephalin has been synthesised as a potentially selective substrate for enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity in brain. Incubations in the presence of homogenates and particulate fractions from rodent and human brain result in the formation of [ 3 H]Tyr-D-Ala-Gly, which can be conveniently isolated by polystyrene bead column chromatography. The enzyme activity responsible for the hydrolysis of the Gly 3 -Phe 4 amide bond of this substrate displays close resemblance to that hydrolysing the natural enkephalins at the same level. In addition, enkephalinase activity characterised in postmortem human brain is closely similar to that in rodent brain, with regard to optimal pH and apparent affinities of various substrates and inhibitors, including the potent compound thiorphan. Enkephalinase activity is distributed in a highly heterogeneous fashion among regions of human brain, the highest levels being found in globus pallidus and pars reticulata of the substantia nigra. This distribution is poorly correlated with that of opiate receptor binding sites but displays some resemblance to that of reported Met 5 -enkephalin levels. (author)

The role of high-field magnetic resonance imaging in parkinsonian disorders

DEFF Research Database (Denmark)

Lehericy, Stéphane; Vaillancourt, David E.; Seppi, Klaus

2017-01-01

changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron-sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful...

Xenotransplantation in Parkinson's disease

NARCIS (Netherlands)

Koopmans, Jan

2006-01-01

Parkinson's disease is a neurodegenerative disorder characterised by loss of dopaminergic neurones in the substantia nigra pars compacta and subsequent shortage of dopamine in the striatum of the these patients causing the well known symptoms first described by James Parkinson in 1817. In this

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

Activin A Inhibits MPTP and LPS-Induced Increases in Inflammatory Cell Populations and Loss of Dopamine Neurons in the Mouse Midbrain In Vivo.

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Stayte, Sandy; Rentsch, Peggy; Tröscher, Anna R; Bamberger, Maximilian; Li, Kong M; Vissel, Bryce

2017-01-01

Parkinson's disease is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta region and a subsequent loss of dopamine within the striatum. A promising avenue of research has been the administration of growth factors to promote the survival of remaining midbrain neurons, although the mechanism by which they provide neuroprotection is not understood. Activin A, a member of the transforming growth factor β superfamily, has been shown to be a potent anti-inflammatory following acute brain injury and has been demonstrated to play a role in the neuroprotection of midbrain neurons against MPP+-induced degeneration in vitro. We hypothesized that activin A may offer similar anti-inflammatory and neuroprotective effects in in vivo mouse models of Parkinson's disease. We found that activin A significantly attenuated the inflammatory response induced by both MPTP and intranigral administration of lipopolysaccharide in C57BL/6 mice. We found that administration of activin A promoted survival of dopaminergic and total neuron populations in the pars compacta region both 8 days and 8 weeks after MPTP-induced degeneration. Surprisingly, no corresponding protection of striatal dopamine levels was found. Furthermore, activin A failed to protect against loss of striatal dopamine transporter expression in the striatum, suggesting the neuroprotective action of activin A may be localized to the substantia nigra. Together, these results provide the first evidence that activin A exerts potent neuroprotection and anti-inflammatory effects in the MPTP and lipopolysaccharide mouse models of Parkinson's disease.

Autoradiographic localization of delta opioid receptors within the mesocorticolimbic dopamine system using radioiodinated (2-D-penicillamine, 5-D-penicillamine)enkephalin ( sup 125 I-DPDPE)

Energy Technology Data Exchange (ETDEWEB)

Dilts, R.P.; Kalivas, P.W. (Washington State Univ., Pullman (USA))

1990-01-01

The enkephalin analog (2-D-penicillamine, 5-D-penicillamine)enkephalin was radioiodinated (125I-DPDPE) and shown to retain a pharmacological selectivity characteristic of the delta opioid receptor in in vitro binding studies. The distributions of 125I-DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of 125I-DPDPE binding in regions known to receive dopaminergic afferents emanating from the mesencephalic tegmentum. Selective chemical lesions of the ventral tegmental area and substantia nigra were employed to deduce the location of the 125I-DPDPE binding within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area and substantia nigra produced by mesencephalic injection of 6-hydroxydopamine resulted in significant (20-30%) increases in 125I-DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by quinolinic acid injections, caused increases of less magnitude within these same nuclei. No significant alterations in 125I-DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confirmed by immunocytochemistry for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists acting through delta opioid receptors do not directly modulate dopaminergic afferents but do regulate postsynaptic targets of the mesocorticolimbic dopamine system.

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.

Dermatosis papulosa nigra in a young child.

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Babapour, R; Leach, J; Levy, H

1993-12-01

Dermatosis papulosa nigra was diagnosed in a 3-year-old black boy. This follicular nevoid condition, which is common in adult blacks, is seldom diagnosed in prepubescent children. The diagnosis was confirmed by the biopsy specimen that showed features of epidermal acanthosis and papillomatosis, similar to seborrheic keratosis.

Injury-stimulated Sonic hedgehog expression in microglia contributes to neuroinflammatory response in the MPTP model of Parkinson's disease

International Nuclear Information System (INIS)

Lee, Jeong Hwi; Chung, Young Cheul; Bok, Eugene; Lee, Hankyu; Huh, Sue Hee; Lee, Ji Eun; Jin, Byung Kwan; Ko, Hyuk Wan

2017-01-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration. Here, we investigated the role of Shh in the pathologic progress of Parkinson's disease in MPTP-induced animal model system. Interestingly, we observed that Shh expression was gradually increased in MPTP affected SNpc region. Activated microglia exclusively expressed SHH in vivo and we could recapitulate Shh induction in activated cultured primary microglia cells. Using the SHH responsive Cre-loxP binary genetic reporter transgenic mouse system, we also found that most of the cell types except for oligodendrocyte in the SNpc region reacted to the SHH by MPTP injection. Taken together, activated microglia induced Shh expression and most neural cells except oligodendrocyte responded to microglia-derived SHH in MPTP-treated SN. These results suggest that SHH in activated microglia by MPTP-injection might be involved in the innate processes of recovery from neurotoxin induced injury in the PD animal model system. - Highlights: • Sonic hedgehog (Shh) was induced by MPTP neurotoxin at the Substantia Nigra (SN) in vivo. • Activated microglia are major cell type for SHH expression in vivo and in vitro. • Different types of cells in the brain, except oligodendrocyte, respond to microglia-derived SHH in SN region.

Familial hemiplegic migraine type 1 associated with parkinsonism

DEFF Research Database (Denmark)

Bruun, Marie; Hjermind, Lena Elisabeth; Thomsen, Carsten

2015-01-01

parkinsonism with rigidity, bradykinesia and a resting tremor. An MRI showed a normal substantia nigra, but a bilateral loss of substance in the basal ganglia, which is in contrast to the typically normal MRI in idiopathic Parkinson's disease. Dopamine transporter (DAT) imaging with single-photon emission...

Presence of melatonin in various cat brainstem nuclei determined by radioimmunoassay

International Nuclear Information System (INIS)

Sallanon, M.; Touret, M.; Claustrat, B.

1982-01-01

Microdissected samples of juvenile cat brain tissue were assayed for melatonin content using a double antibody radioimmunoassay. Immunoreactive melatonin was consistently detected, albeit in variable amounts, in pineal, habenula, the region of the nucleus gracilis, gigantocellular reticular formation of the pons and medulla oblongata. Among the negative areas were raphe nuclei, substantia nigra dn locus caeruleus. These findings suggest that melatonin may play a role in some structures of the central nervous system outside the pineal-hypothalamo-pituitary axis. This immunoreactive melatonin could reflect a local synthesis, or a tissular uptake of melatonin from blood or cerebrospinal fluid. (author)

STRUCTURE IDENTIFICATION OF A TRIMER STILBENOID COMPOUND FROM STEM BARK Hopea nigra (DIPTEROCARPACEAE

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Sri Atun

2010-06-01

Full Text Available Bioactivity as antihephatotoxic directed fractionation of aceton extract from the stem bark of Hopea nigra (Dipterocarpaceae afforded a stilbenoid trimer, namely vaticanol G (1. The structure of this compound were elucidated based on physical and spectroscopic data (UV, IR, MS, 1H and 13C NMR 1D and 2D. Keywords: Vaticanol G; Hopea nigra; antihepatotoxic; Dipterocarpaceae.

Peripheral Inflammation Increases the Damage in Animal Models of Nigrostriatal Dopaminergic Neurodegeneration: Possible Implication in Parkinson's Disease Incidence

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A. Machado

2011-01-01

Full Text Available Inflammatory processes described in Parkinson’s disease (PD and its animal models appear to be important in the progression of the pathogenesis, or even a triggering factor. Here we review that peripheral inflammation enhances the degeneration of the nigrostriatal dopaminergic system induced by different insults; different peripheral inflammations have been used, such as IL-1β and the ulcerative colitis model, as well as insults to the dopaminergic system such as 6-hydroxydopamine or lipopolysaccharide. In all cases, an increased loss of dopaminergic neurons was described; inflammation in the substantia nigra increased, displaying a great activation of microglia along with an increase in the production of cytokines such as IL-1β and TNF-α. Increased permeability or disruption of the BBB, with overexpression of the ICAM-1 adhesion molecule and infiltration of circulating monocytes into the substantia nigra, is also involved, since the depletion of circulating monocytes prevents the effects of peripheral inflammation. Data are reviewed in relation to epidemiological studies of PD.

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. 

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.

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.

Motor function in a patient with bilateral lesions of the globus pallidus

NARCIS (Netherlands)

Haaxma, R; vanBoxtel, A; Brouwer, WH; Goeken, LNH; vanderGon, JJD; Colebatch, JG; Martin, A; Brooks, DJ; Noth, J; Marsden, CD

1995-01-01

This study describes the long-term motor deficits of a patient who, after a toxic encephalopathy, sustained extensive bilateral damage to both segments of the globus pallidus (GP) and the right substantia nigra (SN). There were no signs of lesions of the pyramidal tracts or of other motor

The Transcription Factor Orthodenticle Homeobox 2 Influences Axonal Projections and Vulnerability of Midbrain Dopaminergic Neurons

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Chung, Chee Yeun; Licznerski, Pawel; Alavian, Kambiz N.; Simeone, Antonio; Lin, Zhicheng; Martin, Eden; Vance, Jeffery; Isacson, Ole

2010-01-01

Two adjacent groups of midbrain dopaminergic neurons, A9 (substantia nigra pars compacta) and A10 (ventral tegmental area), have distinct projections and exhibit differential vulnerability in Parkinson's disease. Little is known about transcription factors that influence midbrain dopaminergic subgroup phenotypes or their potential role in disease.…

Development of Brassica oleracea-nigra monosomic alien addition lines: genotypic, cytological and morphological analyses.

Science.gov (United States)

Tan, Chen; Cui, Cheng; Xiang, Yi; Ge, Xianhong; Li, Zaiyun

2017-12-01

We report the development and characterization of Brassica oleracea - nigra monosomic alien addition lines (MAALs) to dissect the Brassica B genome. Brassica nigra (2n = 16, BB) represents the diploid Brassica B genome which carries many useful genes and traits for breeding but received limited studies. To dissect the B genome from B. nigra, the triploid F 1 hybrid (2n = 26, CCB) obtained previously from the cross B. oleracea var. alboglabra (2n = 18, CC) × B. nigra was used as the maternal parent and backcrossed successively to parental B. oleracea. The progenies in BC 1 to BC 3 generations were analyzed by the methods of FISH and SSR markers to screen the monosomic alien addition lines (MAALs) with each of eight different B-genome chromosomes added to C genome (2n = 19, CC + 1B 1-8 ), and seven different MAALs were established, except for the one with chromosome B2 which existed in one triple addition. Most of these MAALs were distinguishable morphologically from each other, as they expressed the characters from B. nigra differently and at variable extents. The alien chromosome remained unpaired as a univalent in 86.24% pollen mother cells at diakinesis or metaphase I, and formed a trivalent with two C-genome chromosomes in 13.76% cells. Transmission frequency of all the added chromosomes was far higher through the ovules (averagely 14.40%) than the pollen (2.64%). The B1, B4 and B5 chromosomes were transmitted by female at much higher rates (22.38-30.00%) than the other four (B3, B6, B7, B8) (5.04-8.42%). The MAALs should be valuable for exploiting the genome structure and evolution of B. nigra.

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%)

Protection of dopaminergic neurons by 5-lipoxygenase inhibitor.

Science.gov (United States)

Kang, Kai-Hsiang; Liou, Horng-Hui; Hour, Mann-Jen; Liou, Houng-Chi; Fu, Wen-Mei

2013-10-01

Neuroinflammation and oxidative stress are important factors that induce neurodegeneration in age-related neurological disorders. 5-Lipoxygenase (5-LOX) is the enzyme responsible for catalysing the synthesis of leukotriene or 5-HETE from arachidonic acid. 5-LOX is expressed in the central nervous system and may cause neurodegenerative disease. In this study, we investigated the effect of the pharmacological inhibition of 5-lipoxygenase on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/MPP(+)-induced dopaminergic neuronal death in midbrain neuron-glia co-cultures and in mice. It was found that 5-LOX was over-expressed in astrocytes after the injection of MPTP into C57BL6 mice. MK-886, a specific inhibitor of 5-LOX activating protein (FLAP), significantly increased [(3)H]-dopamine uptake, a functional indicator of the integrity of dopaminergic neurons, in midbrain cultures or the SH-SY5Y human dopaminergic cell line following MPP(+) treatment. In addition, LTB₄, one of 5-LOX's downstream products, was increased in the striatum and substantia nigra following MPTP injection in mice. LTB₄ but not LTD₄ and 5-HETE enhanced MPP(+)-induced neurotoxicity in primary midbrain cultures. MK-886 administration increased the number of tyrosine hydroxylase-positive neurons in the substantia nigra and the dopamine content in the striatum in MPTP-induced parkinsonian mice. Furthermore, the MPTP-induced upregulation of LTB₄ in the striatum and substantia nigra was antagonised by MK-886. These results suggest that 5-LOX inhibitors may be developed as novel neuroprotective agents and LTB₄ may play an important pathological role in Parkinson's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Magnetic Resonance Imaging Features of the Nigrostriatal System: Biomarkers of Parkinson’s Disease Stages?

Science.gov (United States)

Hopes, Lucie; Grolez, Guillaume; Moreau, Caroline; Lopes, Renaud; Ryckewaert, Gilles; Carrière, Nicolas; Auger, Florent; Laloux, Charlotte; Petrault, Maud; Devedjian, Jean-Christophe; Bordet, Regis; Defebvre, Luc; Jissendi, Patrice; Delmaire, Christine; Devos, David

2016-01-01

Introduction Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson’s disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD. Methods Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients. Results The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages. Conclusion Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease. PMID:27035571

Striatal dopamine transporter, regional cerebral blood flow and glucose utilization in MPTP-induced parkinson disease mice model

International Nuclear Information System (INIS)

Gao Yunchao; Wu Chunying; Xiang Jingde; Lin Xiangtong; Zhu Huiqing

2005-01-01

Objective: To explore the variation of regional cerebral blood flow (rCBF), glucose utilization as well as the neurotoxic effect on dopaminergic neurons induced by neurotoxin 1-methy-4-phenyl-1,2,3,6-tetrahy-dropyridine (MPTP). Methods: Eight-week old male C57BL/6 mice were given a total dose of 0-80 mg/kg MPTP intraperitoneally. Ten days later the mice were sacrificed for tyrosine hydroxylase (TH)-immunopositive cell count- ing in substantia nigra using SP immunohistochemistry. Vivo autoradiography was employed to measure striatal do- pamine transporter (DAT) loss, rCBF and glucose utilization in striatum and thalamus. Results: The extents of DAT depletion and TH-immunopositive cell loss were positively correlated (r=0.998, P O.2), while glucose utilization was only slightly reduced in caudate/putamen and thalamus by 3.0% and 5.4% in 80 mg/kg MPTP-treated mice (P<0.05). Conclusion: Significant dose-dependent relationship was in presence of MPTP induced dopaminergic neurons loss, changes of rCBF in caudate/putamen and thalamus were not significant, while the glucose utilization was slightly decreased in higher dose group. (authors)

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.

Horizontal and Vertical Attentional Orienting in Parkinson's Disease

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Nys, Gudrun M. S.; Santens, Patrick; Vingerhoets, Guy

2010-01-01

Patients with Parkinson's disease (PD) typically suffer from an asymmetric degeneration of dopaminergic cells in the substantia nigra, resulting in right-sided (RPD) or left-sided (LPD) predominance of motor symptomatology. As the dopaminergic system is also involved in attention, we examined horizontal and vertical orienting of attention in LPD…

Behavioral Specifications of Reward-Associated Long-Term Memory Enhancement in Humans

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Wittmann, Bianca C.; Dolan, Raymond J.; Duzel, Emrah

2011-01-01

Recent functional imaging studies link reward-related activation of the midbrain substantia nigra-ventral tegmental area (SN/VTA), the site of origin of ascending dopaminergic projections, with improved long-term episodic memory. Here, we investigated in two behavioral experiments how (1) the contingency between item properties and reward, (2) the…

Activation of Midbrain Structures by Associative Novelty and the Formation of Explicit Memory in Humans

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Schott, Bjorn H.; Sellner, Daniela B.; Lauer, Corinna-J.; Habib, Reza; Frey, Julietta U.; Guderian, Sebastian; Heinze, Hans-Jochen; Duzel, Emrah

2004-01-01

Recent evidence suggests a close functional relationship between memory formation in the hippocampus and dopaminergic neuromodulation originating in the ventral tegmental area and medial substantia nigra of the midbrain. Here we report midbrain activation in two functional MRI studies of visual memory in healthy young adults. In the first study,…

Demyelination of subcortical nuclei in multiple sclerosis

Science.gov (United States)

Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

2016-02-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

Genetic variation of the riparian pioneer tree species populus nigra. II. Variation In susceptibility to the foliar rust melampsora larici-populina

Science.gov (United States)

Legionnet; Muranty; Lefevre

1999-04-01

Partial resistance of Populus nigra L. to three races of the foliar rust Melampsora larici-populina Kleb. was studied in a field trial and in laboratory tests, using a collection of P. nigra originating from different places throughout France. No total resistance was found. The partial resistance was split into epidemiological components, which proved to be under genetic control. Various patterns of association of epidemiological components values were found. Principal components analysis revealed their relationships. Only 24% of the variance of the field susceptibility could be explained by the variation of the epidemiological components of susceptibility. This variable was significantly correlated with susceptibility to the most ancient and widespread race of the pathogen, and with the variables related to the size of the lesions of the different races. Analysis of variance showed significant differences in susceptibility between regions and between stands within one region. Up to 20% of variation was between regions, and up to 22% between stands, so that these genetic factors appeared to be more differentiated than the neutral diversity (up to 3.5% Legionnet & Lefevre, 1996). However, no clear pattern of geographical distribution of diversity was detected.

Non-Motor Symptom Burdens Are Not Associated with Iron Accumulation in Early Parkinson's Disease: a Quantitative Susceptibility Mapping Study.

Science.gov (United States)

Shin, Chaewon; Lee, Seon; Lee, Jee Young; Rhim, Jung Hyo; Park, Sun Won

2018-03-26

Quantitative susceptibility mapping (QSM) has been used to measure iron accumulation in the deep nuclei of patients with Parkinson's disease (PD). This study examined the relationship between non-motor symptoms (NMSs) and iron accumulation in the deep nuclei of patients with PD. The QSM data were acquired from 3-Tesla magnetic resonance imaging (MRI) in 29 patients with early PD and 19 normal controls. The Korean version of the NMS scale (K-NMSS) was used for evaluation of NMSs in patients. The patients were divided into high NMS and low NMS groups. The region-of-interest analyses were performed in the following deep nuclei: red nucleus, substantia nigra pars compacta, substantia nigra pars reticulata, dentate nucleus, globus pallidus, putamen, and head of the caudate nucleus. Thirteen patients had high NMS scores (total K-NMSS score, mean = 32.1), and 16 had low NMS scores (10.6). The QSM values in the deep were not different among the patients with high NMS scores, low NMS scores, and controls. The QSM values were not correlated linearly with K-NMSS total score after adjusting the age at acquisition of brain MRI. The study demonstrated that the NMS burdens are not associated with iron accumulation in the deep nuclei of patients with PD. These results suggest that future neuroimaging studies on the pathology of NMSs in PD should use more specific and detailed clinical tools and recruit PD patients with severe NMSs. © 2018 The Korean Academy of Medical Sciences.

Insights into some physiological and biochemical responses of Populus alba and Populus nigra to lead contamination

Directory of Open Access Journals (Sweden)

Elham Etemadi

2016-12-01

Full Text Available The effects of lead (PbCl2 increment, under hydroponic conditions up to 15, 45 and 90 mg/l in presence of EDTA, on some physiological and biochemical traits of one year old saplings of P. nigra and P. alba, were investigated. Six weeks after establishing in target concentration, the amount of lead, biomass, water, soluble sugars, proline, electrolyte leakage, malondialdehyde, and pigments were assessed in different organs. The results revealed that with increasing lead concentration in culture medium in the studied period, the amount of lead in saplings increased, but no effect was observed on their biomass. In both species the magnitude of lead accumulation in root was higher than leaf. P. nigra had more water and less soluble sugars than P. alba. The concentration of soluble sugars increased up to 1.5 times with lead increment in both species, but proline content increased only in P. nigra up to 2 times and remained constant in P. alba. Elevation of electrolyte leakage in saplings of P. nigra in excess lead treatment was accompanied by no change in malondialdehyde content. Concentrations of pigments were not affected by lead, and only the ratio of chlorophyll a to b in P. nigra increased in high lead concentration. In general both species accumulated high extent of lead in their organs. But it seems that P. nigra, at least with respect of enhancing plasma membrane permeability, increasing proline and the ratio of chlorophyll a to b, was more sensitive to this toxic metal in compare with P. alba.

Future scenarios and conservation strategies for a rear-edge marginal population of Pinus nigra Arnold in Italian central Apennines

Energy Technology Data Exchange (ETDEWEB)

Marchi, M.; Nocentini, S.; Ducci, F.

2016-07-01

Aim of the study: To forecast the effects of climate change on the spatial distribution of Black pine of Villetta Barrea in its natural range and to define a possible conservation strategy for the species. Area of study: A rear-edge marginal population of Pinus nigra spp. nigra in Abruzzo region, central Italian Apennines. Matherials and Methods: For its adaptive and genetic traits this population is considered endemic of the Italian peninsula and represents a rear-edge marginal population of nigra subspecies. The spatial distribution of the tree in the administrative Region (Abruzzo) was used to define the ecological traits while three modelling techniques (GLM, GAM, Random Forest) were used to build a Species distribution model according to two climatic scenarios. Main results: The marginal population's range was predicted to shift at higher elevations as consequence of climatic adaptation. Many zones, represented by the higher part of the mountains surrounding the study area (currently bare and inhospitable for trees), were identified as suitable in future for the species. However, in the case of a rapid climate change, this marginal population may not be able to move as fast as necessary. An in-situ adaptive management integrated with an assisted migration protocol might be considered to enforce the natural regeneration and improve the richness and variability of the genetic pool. Research highlights: Most of the genetic richness is held in small populations at the borders of natural distribution of forest species. Monitoring this MAP could be useful to understand the adaptive processes of the species and could support the future management of many other within-core populations. (Author)

Future scenarios and conservation strategies for a rear-edge marginal population of Pinus nigra Arnold in Italian central Apennines

Directory of Open Access Journals (Sweden)

Maurizio Marchi

2016-12-01

Full Text Available Aim of study: To forecast the effects of climate change on the spatial distribution of Black pine of Villetta Barrea in its natural range and to define a possible conservation strategy for the species Area of study: A rear-edge marginal population of Pinus nigra spp. nigra in Abruzzo region, central Italian Apennines Matherials and Methods: For its adaptive and genetic traits this population is considered endemic of the Italian peninsula and represents a rear-edge marginal population of nigra subspecies. The spatial distribution of the tree in the administrative Region (Abruzzo was used to define the ecological traits while three modelling techniques (GLM, GAM, Random Forest were used to build a Species distribution model according to two climatic scenarios. Main results: The marginal population's range was predicted to shift at higher elevations as consequence of climatic adaptation. Many zones, represented by the higher part of the mountains surrounding the study area (currently bare and inhospitable for trees, were identified as suitable in future for the species. However, in the case of a rapid climate change, this marginal population may not be able to move as fast as necessary. An in-situ adaptive management integrated with an assisted migration protocol might be considered to enforce the natural regeneration and improve the richness and variability of the genetic pool. Research highlights: Most of the genetic richness is held in small populations at the borders of natural distribution of forest species. Monitoring this MAP could be useful to understand the adaptive processes of the species and could support the future management of many other within-core populations. Keywords: Species Distribution Models; Mediterranean forests; Abruzzo; climate change; altitudinal shift.

Alterations in hypothalamic gene expression following Roux-en-Y gastric bypass

DEFF Research Database (Denmark)

Barkholt, Pernille; Pedersen, Philip J.; Hay-Schmidt, Anders

2016-01-01

increase of orexigenic MCH mRNA levels in food-restricted animals, RYGB did not change MCH expression in the lateral hypothalamus. In the VTA, RYGB surgery induced a reduction in mRNA levels of TH and DAT, whereas no changes were observed in the substantia nigra relative to sham surgery.  Conclusion: RYGB...

Retrograde axoplasmic flow of serotonin in central mono-aminergic neurons

International Nuclear Information System (INIS)

Leger, Lucienne; Pujol, J.-F.; Bobillier, Pierre; Jouvet, Michel

1977-01-01

Following an injection of 3 H-5 HT in the neostriatum of the Rat, the tracer is transported by axoplasmic retrograde flow to the cell groups containing mono-aminergic neurons which are known or thought to have afferences to this structure: substantia nigra, dopaminergic group A8 and n. raphe dorsalis [fr

Demyelination of subcortical nuclei in multiple sclerosis

International Nuclear Information System (INIS)

Krutenkova, E; Aitmagambetova, G; Khodanovich, M; Yarnykh, V; Bowen, J; Gangadharan, B; Henson, L; Mayadev, A; Repovic, P; Qian, P

2016-01-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus. (paper)

Neurobehavioral performances and brain regional metabolism in Dab1(scm) (scrambler) mutant mice.

Science.gov (United States)

Jacquelin, C; Lalonde, R; Jantzen-Ossola, C; Strazielle, C

2013-09-01

As disabled-1 (DAB1) protein acts downstream in the reelin signaling pathway modulating neuronal migration, glutamate neurotransmission, and cytoskeletal function, the disabled-1 gene mutation (scrambler or Dab1(scm) mutation) results in ataxic mice displaying dramatic neuroanatomical defects similar to those observed in the reeler gene (Reln) mutation. By comparison to non-ataxic controls, Dab1(scm) mutants showed severe motor coordination impairments on stationary beam, coat-hanger, and rotorod tests but were more active in the open-field. Dab1(scm) mutants were also less anxious in the elevated plus-maze but with higher latencies in the emergence test. In mutants versus controls, changes in regional brain metabolism as measured by cytochrome oxidase (COX) activity occurred mainly in structures intimately connected with the cerebellum, in basal ganglia, in limbic regions, particularly hippocampus, as well as in visual and parietal sensory cortices. Although behavioral results characterized a major cerebellar disorder in the Dab1(scm) mutants, motor activity impairments in the open-field were associated with COX activity changes in efferent basal ganglia structures such as the substantia nigra, pars reticulata. Metabolic changes in this structure were also associated with the anxiety changes observed in the elevated plus-maze and emergence test. These results indicate a crucial participation of the basal ganglia in the functional phenotype of ataxic Dab1(scm) mutants. Copyright © 2013 Elsevier B.V. All rights reserved.

Antioxidant effect of Morus nigra on Chagas disease progression.

Science.gov (United States)

Montenote, Michelly Cristina; Wajsman, Vithor Zuccaro; Konno, Yoichi Takaki; Ferreira, Paulo César; Silva, Regildo Márcio Gonçalves; Therezo, Altino Luiz Silva; Silva, Luciana Pereira; Martins, Luciamáre Perinetti Alves

2017-11-06

Considering the widespread popular use of Morus nigra and the amount of scientific information on its antioxidant and anti-inflammatory activity, the effectiveness of this phytotherapeutic compound in the parasitemia progression during the acute phase of Chagas disease and its role in the development of the inflammatory process as well as its effects on the oxidative damage in the chronic phase of infection were evaluated. Thus, 96 male Swiss mice were randomly divided into eight groups, four groups were uninfected controls, and four groups were intraperitoneally infected with 5.0 x 104 blood trypomastigotes forms of T. cruzi QM2 strain. Four batches composed of one uninfected and one infected group were respectively treated with 70% alcohol solution and 25 μL, 50 μL and 75 μL of the phytotherapeutic compound. Levels of antioxidant elements (TBARS, FRAP, GSH and Sulfhydryl groups) were measured in plasma samples. The phytotherapeutic compound's antioxidant activity was measured by polyphenol and total flavonoid quantification, DPPH, NO, and FRAP method. Our results showed that the vehicle influenced some of the results that may have physiological relevance in Chagas disease. However, an important action of M. nigra tincture was observed in the progression of Chagas disease, since our results demonstrated a reduction in parasitemia of treated groups when compared to controls, especially in the group receiving 25 µL. However, in the chronic phase, the 50-µL dosage presented a better activity on some antioxidant defenses and minimized the tissue inflammatory process. Results indicated an important action of M. nigra tincture on the Chagas disease progression.

An adaption of the push-pull cannula method to study the in vivo release of [3H]dopamine synthesised from [3H]tyrosine in the cat caudate nucleus: effects of various physical and pharmacological treatments

International Nuclear Information System (INIS)

Nieoullon, A.; Cheramy, A.; Glowinski, J.

1977-01-01

The release of [ 3 H]dopamine ([ 3 H]DA) continuously synthesized from L-[3,5- 3 H]tyrosine from the caudate nucleus of the cat was estimated in halothane anaesthetized or 'encephale isole' animals. For this purpose, an improved superfusion cannula, avoiding tissue damage, was used. The best localization for the tip of the superfusion cannula was found first by determining the topographical distribution of endogenous DA within the caudate nucleus. A rostro-caudal heterogenous distribution of the transmitter was detected. In perfusion experiments, L-[3, 5 3 H]tyrosine was introduced continuously at a rate of 33 μl/min. [ 3 H]DA was the only catecholamine found in serial 15 min fractions as revealed by cochromatography. The spontaneous release of [ 3 H]DA was greater in anaesthetized than in 'encephale isole'cats; it represented 150 and 100 times the blank value, respectively. Depolarization by K + (30 mM) applied locally in the striatum or by electrical or mechanical stimulation of the substantia nigra caused a transitory increase in [ 3 H]DA release. Conversely, a decrease in nerve activity induced by tetrodotoxin (5 x 10 -7 M) or by electrocoagulation of the substantia nigra was associated with a decline in the amounts of [ 3 H]DA in superfusates. A temporary reduction in [ 3 H]DA release could also be obtained by a short-lasting cooling block of the substantia nigra. As expected, d-amphetamine (10 -5 M) and benzotropine (10 -6 M) added to the superfusing medium increased [ 3 H]DA release. These pharmacological results, as well as the changes in [ 3 H]DA release observed after various manipulations of the activity of dopaminergic neurones, confirms the validity and the high sensitivity of this approach. (author)

MR imaging of extrapyramidal disorders

Energy Technology Data Exchange (ETDEWEB)

Ikeda, Ken; Kinoshita, Masao; Iwasaki, Yasuo; Shiojima, Toshiya (Toho Univ., Tokyo (Japan). Ohashi Hospital); Sunahara, Nobuhiko

1992-04-01

Magnetic resonance imaging (MRI) was performed in a total of 35 patients with extrapyramidal disorder, including Parkinson's disease (n=15), multiple system atrophy (MSA, n=12), progressive supranuclear palsy (PSP, n=5), and dentatoruburopallidoluysian atrophy (DRPLA, n=3). MR images 5-10 mm in thickness were obtained in both axial and coronal sections. In all patients with Parkinson's disease, there was non-specific age-related cortical atrophy on T[sub 1]-weighted images. T[sub 2]-weighted imaging showed not only putaminal hypointensity, but also linear hyperintensity in the lateral part of putamen. However, these MR findings were not considered pathognomonic. All MSA patients showed atrophy of the brainstem and cerbellum on T[sub 1]-weighted images. Both proton density and T[sub 2]-weighted image showed increased signal intensity in the pontine transverse fibers between the tegmentum and basis pontis. These findings were correlated with atrophy degree of brainstem and middle cerebellar peduncles. It was also difficult to distinguish hyperintesnity in red nuclei from substantia nigra on T[sub 2]-weighted images. Severe atrophy of tegmentum of midbrain and high signal intensity area in the periaqueductal zone were found in all PSP patients on proton density images. Distinction between low signal areas of red nuclei and substantia nigra were obscure in these patients. In some cases of MSA and PSP, small oval hypointensity signals were also found in the superior colliculi. All DRPLA patients had cortical and cerebellar atrophy, but normal brainstem on T[sub 1]-weighted images. On proton density and T[sub 2]-weighted images, hyperintensity signal areas were found in the superior cerebellar peduncles. There was signal restoration in the dentate nuclei on T[sub 2]-weighted images. There was no specific change of signal intensity in the red nuclei, substantia nigra, basal ganglia, and cerebral white matter. (N.K.).

Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism.

Science.gov (United States)

Fernández-Espejo, Emilio; Bis-Humbert, Cristian

2018-06-06

3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cultured substantia nigra neurons, the enteric nervous system of the jejunum after intra-peritoneal infusions, and the nigrostriatal system following unilateral intrabrain injections. 3-iodo-l-tyrosine, a physiological molecule, was used at concentrations higher than its serum levels in humans. Parkinson-like signs were evaluated through abnormal aggregation of α-synuclein and tyrosine-hydroxylase, loss of tyrosine-hydroxylase-expressing and striatum-projecting neurons and fibers, reduced tyrosine-hydroxylase density, and Parkinson-like motor and non-motor deficits. The retrograde tracer FluoroGold was used in the brain model. The findings revealed that excess amounts of 3-iodo-l-tyrosine induce Parkinson-like effects in the three experimental approaches. Thus, culture neurons of substantia nigra show, after 3-iodo-l-tyrosine exposure, intracytoplasmic inclusions that express α-synuclein and tyrosine-hydroxylase. Intra-peritoneal infusions of 3-iodo-l-tyrosine cause, in the long-term, α-synuclein aggregation, thicker α-synuclein-positive fibers, and loss of tyrosine-hydroxylase-positive cells and fibers in intramural plexuses and ganglia of the jejunum. Infusion of 3-iodo-l-tyrosine into the left dorsal striata of mice damages the nigrostriatal system, as revealed through lower striatal tyrosine-hydroxylase density, reduced number of tyrosine-hydroxylase-expressing and striatum-projecting neurons in the left substantia nigra, as well as the emergence of Parkinson-like behavioral deficits such as akinesia, bradykinesia, motor disbalance, and locomotion directional bias. In conclusion, excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in

Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease

Science.gov (United States)

Bayliss, Jacqueline A.; Lemus, Moyra B.; Stark, Romana; Santos, Vanessa V.; Thompson, Aiysha; Rees, Daniel J.; Galic, Sandra; Elsworth, John D.; Kemp, Bruce E.; Davies, Jeffrey S.

2016-01-01

Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with neuroprotective properties, during CR prevents neurodegeneration in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR's neuroprotective effect. CR elevated phosphorylated AMPK and ACC levels in the striatum of WT but not KO mice suggesting that AMPK is a target for ghrelin-induced neuroprotection. Indeed, exogenous ghrelin significantly increased pAMPK in the SN. Genetic deletion of AMPKβ1 and 2 subunits only in dopamine neurons prevented ghrelin-induced AMPK phosphorylation and neuroprotection. Hence, ghrelin signaling through AMPK in SN dopamine neurons mediates CR's neuroprotective effects. We consider targeting AMPK in dopamine neurons may recapitulate neuroprotective effects of CR without requiring dietary intervention. SIGNIFICANCE STATEMENT The neuroprotective mechanisms of calorie restriction (CR) in Parkinson's disease are unknown. Indeed, the difficulty to adhere to CR necessitates an alternative method to recapitulate the neuroprotective benefits of CR while bypassing dietary constraints. Here we show that CR increases plasma ghrelin, which targets substantia nigra dopamine to maintain neuronal survival. Selective deletion on AMPK beta1 and beta2 subunits only in DAT cre-expressing neurons shows that the ghrelin-induced neuroprotection requires activation of AMPK in substantia nigra dopamine neurons. We have discovered ghrelin as a key metabolic signal, and AMPK in dopamine neurons as its target, which links calorie restriction with neuroprotection in Parkinson's disease. Thus, targeting AMPK in dopamine neurons may provide novel neuroprotective benefits in Parkinson's disease. PMID

MR imaging of extrapyramidal disorders

International Nuclear Information System (INIS)

Ikeda, Ken; Kinoshita, Masao; Iwasaki, Yasuo; Shiojima, Toshiya; Sunahara, Nobuhiko.

1992-01-01

Magnetic resonance imaging (MRI) was performed in a total of 35 patients with extrapyramidal disorder, including Parkinson's disease (n=15), multiple system atrophy (MSA, n=12), progressive supranuclear palsy (PSP, n=5), and dentatoruburopallidoluysian atrophy (DRPLA, n=3). MR images 5-10 mm in thickness were obtained in both axial and coronal sections. In all patients with Parkinson's disease, there was non-specific age-related cortical atrophy on T 1 -weighted images. T 2 -weighted imaging showed not only putaminal hypointensity, but also linear hyperintensity in the lateral part of putamen. However, these MR findings were not considered pathognomonic. All MSA patients showed atrophy of the brainstem and cerbellum on T 1 -weighted images. Both proton density and T 2 -weighted image showed increased signal intensity in the pontine transverse fibers between the tegmentum and basis pontis. These findings were correlated with atrophy degree of brainstem and middle cerebellar peduncles. It was also difficult to distinguish hyperintesnity in red nuclei from substantia nigra on T 2 -weighted images. Severe atrophy of tegmentum of midbrain and high signal intensity area in the periaqueductal zone were found in all PSP patients on proton density images. Distinction between low signal areas of red nuclei and substantia nigra were obscure in these patients. In some cases of MSA and PSP, small oval hypointensity signals were also found in the superior colliculi. All DRPLA patients had cortical and cerebellar atrophy, but normal brainstem on T 1 -weighted images. On proton density and T 2 -weighted images, hyperintensity signal areas were found in the superior cerebellar peduncles. There was signal restoration in the dentate nuclei on T 2 -weighted images. There was no specific change of signal intensity in the red nuclei, substantia nigra, basal ganglia, and cerebral white matter. (N.K.)

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.

MR imaging of extrapyramidal disorders

Energy Technology Data Exchange (ETDEWEB)

Ikeda, Ken; Kinoshita, Masao; Iwasaki, Yasuo; Shiojima, Toshiya [Toho Univ., Tokyo (Japan). Ohashi Hospital; Sunahara, Nobuhiko

1992-04-01

Magnetic resonance imaging (MRI) was performed in a total of 35 patients with extrapyramidal disorder, including Parkinson's disease (n=15), multiple system atrophy (MSA, n=12), progressive supranuclear palsy (PSP, n=5), and dentatoruburopallidoluysian atrophy (DRPLA, n=3). MR images 5-10 mm in thickness were obtained in both axial and coronal sections. In all patients with Parkinson's disease, there was non-specific age-related cortical atrophy on T[sub 1]-weighted images. T[sub 2]-weighted imaging showed not only putaminal hypointensity, but also linear hyperintensity in the lateral part of putamen. However, these MR findings were not considered pathognomonic. All MSA patients showed atrophy of the brainstem and cerbellum on T[sub 1]-weighted images. Both proton density and T[sub 2]-weighted image showed increased signal intensity in the pontine transverse fibers between the tegmentum and basis pontis. These findings were correlated with atrophy degree of brainstem and middle cerebellar peduncles. It was also difficult to distinguish hyperintesnity in red nuclei from substantia nigra on T[sub 2]-weighted images. Severe atrophy of tegmentum of midbrain and high signal intensity area in the periaqueductal zone were found in all PSP patients on proton density images. Distinction between low signal areas of red nuclei and substantia nigra were obscure in these patients. In some cases of MSA and PSP, small oval hypointensity signals were also found in the superior colliculi. All DRPLA patients had cortical and cerebellar atrophy, but normal brainstem on T[sub 1]-weighted images. On proton density and T[sub 2]-weighted images, hyperintensity signal areas were found in the superior cerebellar peduncles. There was signal restoration in the dentate nuclei on T[sub 2]-weighted images. There was no specific change of signal intensity in the red nuclei, substantia nigra, basal ganglia, and cerebral white matter. (N.K.).

Complete mitochondrial genome sequence of black mustard (Brassica nigra; BB) and comparison with Brassica oleracea (CC) and Brassica carinata (BBCC).

Science.gov (United States)

Yamagishi, Hiroshi; Tanaka, Yoshiyuki; Terachi, Toru

2014-11-01

Crop species of Brassica (Brassicaceae) consist of three monogenomic species and three amphidiploid species resulting from interspecific hybridizations among them. Until now, mitochondrial genome sequences were available for only five of these species. We sequenced the mitochondrial genome of the sixth species, Brassica nigra (nuclear genome constitution BB), and compared it with those of Brassica oleracea (CC) and Brassica carinata (BBCC). The genome was assembled into a 232 145 bp circular sequence that is slightly larger than that of B. oleracea (219 952 bp). The genome of B. nigra contained 33 protein-coding genes, 3 rRNA genes, and 17 tRNA genes. The cox2-2 gene present in B. oleracea was absent in B. nigra. Although the nucleotide sequences of 52 genes were identical between B. nigra and B. carinata, the second exon of rps3 showed differences including an insertion/deletion (indel) and nucleotide substitutions. A PCR test to detect the indel revealed intraspecific variation in rps3, and in one line of B. nigra it amplified a DNA fragment of the size expected for B. carinata. In addition, the B. carinata lines tested here produced DNA fragments of the size expected for B. nigra. The results indicate that at least two mitotypes of B. nigra were present in the maternal parents of B. carinata.

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.

123-I ioflupane (Datscan® presynaptic nigrostriatal imaging in patients with movement disorders

Directory of Open Access Journals (Sweden)

Angel Soriano Castrejón

2005-10-01

Full Text Available 123-I Ioflupane (Datscan® presynaptic imaging has been shown to have a significant utility in the assessment of patients with movement disorders 123-I Ioflupane SPECT is able to distinguish between Parkinson’s disease (PD and other forms of parkinsonism without degeneration of the nigrostriatal pathway, including a common movement disorder such as essential tremor, and to assess disease progression in PD and other neurodegenerative disorders involving the substantia nigra.A imagem pré-sináptica através de 123-I Ioflupane (Datscan® tem mostrado um papel significante na avaliação de pacientes com distúrbios do movimento. 123-I Ioflupane SPECT é capaz de distinguir entre Mal de Parkinson (MP e outras formas de parkinsonismo sem degenerações da via nigroestriatal incluindo um distúrbio comum de movimento parecido com o tremor essencial e para medir a evolução da doença no Mal de Parkinson e outros distúrbios neurodegenerativos envolvendo a substantia nigra.

HIV-1 gp120 neurotoxicity proximally and at a distance from the point of exposure: protection by rSV40 delivery of antioxidant enzymes.

Science.gov (United States)

Louboutin, Jean-Pierre; Agrawal, Lokesh; Reyes, Beverly A S; Van Bockstaele, Elisabeth J; Strayer, David S

2009-06-01

Toxicity of HIV-1 envelope glycoprotein (gp120) for substantia nigra (SN) neurons may contribute to the Parkinsonian manifestations often seen in HIV-1-associated dementia (HAD). We studied the neurotoxicity of gp120 for dopaminergic neurons and potential neuroprotection by antioxidant gene delivery. Rats were injected stereotaxically into their caudate-putamen (CP); CP and (substantia nigra) SN neuron loss was quantified. The area of neuron loss extended several millimeters from the injection site, approximately 35% of the CP area. SN neurons, outside of this area of direct neurotoxicity, were also severely affected. Dopaminergic SN neurons (expressing tyrosine hydroxylase, TH, in the SN and dopamine transporter, DAT, in the CP) were mostly affected: intra-CP gp120 caused approximately 50% DAT+ SN neuron loss. Prior intra-CP gene delivery of Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1) protected SN neurons from intra-CP gp120. Thus, SN dopaminergic neurons are highly sensitive to HIV-1 gp120-induced neurotoxicity, and antioxidant gene delivery, even at a distance, is protective.

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.

Neuroprotective effects of the antiparkinson drug Mucuna pruriens.

Science.gov (United States)

Manyam, Bala V; Dhanasekaran, Muralikrishnan; Hare, Theodore A

2004-09-01

Mucuna pruriens possesses significantly higher antiparkinson activity compared with levodopa in the 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. The present study evaluated the neurorestorative effect of Mucuna pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned rats. Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but did not affect the total monoamine oxidase activity (in vitro). Unlike synthetic levodopa treatment, Mucuna pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine and serotonin content in the substantia nigra. Nicotine adenine dinucleotide (NADH) and coenzyme Q-10, that are shown to have a therapeutic benefit in Parkinson's disease, were present in the Mucuna pruriens cotyledon powder. Earlier studies showed that Mucuna pruriens treatment controls the symptoms of Parkinson's disease. This additional finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra may be due to increased complex-I activity and the presence of NADH and coenzyme Q-10. Copyright (c) 2004 John Wiley & Sons, Ltd.

6-hydroxydopamine-induced degeneration of nigral dopamine neurons: differential effect on nigral and striatal D-1 dopamine receptors

International Nuclear Information System (INIS)

Porceddu, M.L.; Giorgi, O.; De Montis, G.; Mele, S.; Cocco, L.; Ongini, E.; Biggio, G.

1987-01-01

Dopamine-sensitive adenylate cyclase and 3 H-SCH 23390 binding parameters were measured in the rat substantia nigra and striatum 15 days after the injection of 6-hydroxydopamine into the medial forebrain bundle. The activity of nigral dopamine-sensitive adenylate cyclase and the binding of 3 H-SCH 23390 to rat nigral D-1 dopamine receptors were markedly decreased after the lesion. On the contrary, 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway enhanced both adenylate cyclase activity and the density of 3 H-SCH 23390 binding sites in striatal membrane preparations. The changes in 3 H-SCH 23390 binding found in both nigral and striatal membrane preparations were associated with changes in the total number of binding sites with no modifications in their apparent affinity. The results indicate that: a) within the substantia nigra a fraction (30%) of D-1 dopamine receptors coupled to the adenylate cyclase is located on cell bodies and and/or dendrites of dopaminergic neurons; b) striatal D-1 dopamine receptors are tonically innervated by nigrostriatal afferent fibers. 24 references, 1 figure, 1 table

Potential allelochemicals from Sambucus nigra.

Science.gov (United States)

D'Abrosca, B; DellaGreca, M; Fiorentino, A; Monaco, P; Previtera, L; Simonet, A M; Zarrelli, A

2001-12-01

Twenty-four aromatic metabolites belonging to cyanogenins, lignans, flavonoids, and phenolic glycosides were obtained from Sambucus nigra. Structures were determined on the basis of their spectroscopic features. Two compounds have been isolated and identified as (2S)-2-O-beta-D-glucopyranosyl-2-hydroxyphenylacetic acid and benzyl 2-O-beta-D-glucopyranosyl-2,6-dihydroxybenzoate. All the compounds have been assayed on dicotyledons Lactuca sativa (lettuce) and Raphanus sativus (radish) and monocotyledon Allium cepa (onion) to test their stimulatory or inhibitory effects on seed germination and radicle elongation. Cyanogenins have a mainly inhibiting effect while lignans stimulate the growth. Some compounds show different effects on dicotyledons and monocotyledons.

Dopamine mediated iron release from ferritin is enhanced at higher temperatures: Possible implications for fever-induced Parkinson's disease

International Nuclear Information System (INIS)

Babincova, Melania; Babinec, Peter

2005-01-01

A new molecular mechanism is proposed to explain the pathogenesis of fever-induced Parkinson's disease. This proposal is based on dopamine and 6-hydroxydopamine-mediated free iron release from ferritin magnetic nanoparticles, which is enhanced at higher temperatures, and which may lead to substantial peroxidation and injury of lipid biomembranes of the substantia nigra in the brain

Pharmacognostical Investigations on Sambucus ebulus L. and Sambucus nigra L

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Dr. A. R. Ghannadi

1997-08-01

Full Text Available Several species of the genus Sambucus have been used in treating symptoms of the common cold and some skin ailments. Four species of this plant are growing extensively in Iran. One of these species is S.ebulus. In this study, S. ebulus was examined botanically and phytochemicatly in comparison to S. nigra."nMorphological as well as microscopical characteristics of S. ebulus and S. nigra were examined. By means of TLC in comparison to authentic samples, Rutin, Hyperin. Apigenin and Chlorogenic acid were identified in these plants. By preparative TLC method, Rutin is isolated and then purified from these plants. The structure of Rutin was determined by the UV-Vis. Techniques in methanol and by addition of the shift reagents and hydrolysis. The quantitative determinations of fiavonoids in these plants were also performed by using an UV-Vis. Spectroscopy method.

Wood Anatomical Structure of Morus alba L. and Morus nigra L., Native to Iran

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Elham KARAMI

2010-12-01

Full Text Available Iran is a wast country with many different tree species. Among those there are two species of Morus genus including alba and nigra. Since long time ago, white mulberry�s wood (Morus alba has been used for making musical instruments especially bowl shaped instruments in Iran.. In contrast, black mulberry�s wood (Morus nigra has never been used for these types of applications. In order to investigate the possible replacement choices, this study has been carried out to investigate the anatomical differences and similarities between these two species. Wood samples of the two species have been collected from same site and microsections for light microscopic studies and maceration samples have been prepared. The anatomical characteristics were studied according to the IAWA List of Hardwoods. The most important similarities between them are: vessel solitary in short radial multiples or irregular clusters, fiber nonseptate, rays uniseriate and multiseriate type, paratracheal parenchyma, varying from vasicentric to aliform confluent, apotracheal as marginal bands, Rhombic crystals present in rays and sometimes in parenchyma. The main differences are: semi-ring porous distribution of vessels in M. alba, fewer number of vessels and presence of aliform parenchyma in M. nigra. Taking these results into consideration, the most important features of both species are similar and it could be recommended to use the nigra species as well as the alba for making musical instruments.

Wood identification of Dalbergia nigra (CITES Appendix I) using quantitative wood anatomy, principal components analysis and naive Bayes classification.

Science.gov (United States)

Gasson, Peter; Miller, Regis; Stekel, Dov J; Whinder, Frances; Zieminska, Kasia

2010-01-01

Dalbergia nigra is one of the most valuable timber species of its genus, having been traded for over 300 years. Due to over-exploitation it is facing extinction and trade has been banned under CITES Appendix I since 1992. Current methods, primarily comparative wood anatomy, are inadequate for conclusive species identification. This study aims to find a set of anatomical characters that distinguish the wood of D. nigra from other commercially important species of Dalbergia from Latin America. Qualitative and quantitative wood anatomy, principal components analysis and naïve Bayes classification were conducted on 43 specimens of Dalbergia, eight D. nigra and 35 from six other Latin American species. Dalbergia cearensis and D. miscolobium can be distinguished from D. nigra on the basis of vessel frequency for the former, and ray frequency for the latter. Principal components analysis was unable to provide any further basis for separating the species. Naïve Bayes classification using the four characters: minimum vessel diameter; frequency of solitary vessels; mean ray width; and frequency of axially fused rays, classified all eight D. nigra correctly with no false negatives, but there was a false positive rate of 36.36 %. Wood anatomy alone cannot distinguish D. nigra from all other commercially important Dalbergia species likely to be encountered by customs officials, but can be used to reduce the number of specimens that would need further study.

Harsh corporal punishment is associated with increased T2 relaxation time in dopamine-rich regions.

Science.gov (United States)

Sheu, Yi-Shin; Polcari, Ann; Anderson, Carl M; Teicher, Martin H

2010-11-01

Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse. Copyright 2010 Elsevier Inc. All rights reserved.

Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

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Dimitri Ryczko

2017-05-01

Full Text Available In vertebrates, dopamine neurons are classically known to modulate locomotion via their ascending projections to the basal ganglia that project to brainstem locomotor networks. An increased dopaminergic tone is associated with increase in locomotor activity. In pathological conditions where dopamine cells are lost, such as in Parkinson's disease, locomotor deficits are traditionally associated with the reduced ascending dopaminergic input to the basal ganglia. However, a descending dopaminergic pathway originating from the substantia nigra pars compacta was recently discovered. It innervates the mesencephalic locomotor region (MLR from basal vertebrates to mammals. This pathway was shown to increase locomotor output in lampreys, and could very well play an important role in mammals. Here, we provide a detailed account on the newly found dopaminergic pathway in lamprey, salamander, rat, monkey, and human. In lampreys and salamanders, dopamine release in the MLR is associated with the activation of reticulospinal neurons that carry the locomotor command to the spinal cord. Dopamine release in the MLR potentiates locomotor movements through a D1-receptor mechanism in lampreys. In rats, stimulation of the substantia nigra pars compacta elicited dopamine release in the pedunculopontine nucleus, a known part of the MLR. In a monkey model of Parkinson's disease, a reduced dopaminergic innervation of the brainstem locomotor networks was reported. Dopaminergic fibers are also present in human pedunculopontine nucleus. We discuss the conserved locomotor role of this pathway from lamprey to mammals, and the hypothesis that this pathway could play a role in the locomotor deficits reported in Parkinson's disease.

A decision tree for differentiating multiple system atrophy from Parkinson's disease using 3-T MR imaging.

Science.gov (United States)

Nair, Shalini Rajandran; Tan, Li Kuo; Mohd Ramli, Norlisah; Lim, Shen Yang; Rahmat, Kartini; Mohd Nor, Hazman

2013-06-01

To develop a decision tree based on standard magnetic resonance imaging (MRI) and diffusion tensor imaging to differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). 3-T brain MRI and DTI (diffusion tensor imaging) were performed on 26 PD and 13 MSA patients. Regions of interest (ROIs) were the putamen, substantia nigra, pons, middle cerebellar peduncles (MCP) and cerebellum. Linear, volumetry and DTI (fractional anisotropy and mean diffusivity) were measured. A three-node decision tree was formulated, with design goals being 100 % specificity at node 1, 100 % sensitivity at node 2 and highest combined sensitivity and specificity at node 3. Nine parameters (mean width, fractional anisotropy (FA) and mean diffusivity (MD) of MCP; anteroposterior diameter of pons; cerebellar FA and volume; pons and mean putamen volume; mean FA substantia nigra compacta-rostral) showed statistically significant (P decision tree. Threshold values were 14.6 mm, 21.8 mm and 0.55, respectively. Overall performance of the decision tree was 92 % sensitivity, 96 % specificity, 92 % PPV and 96 % NPV. Twelve out of 13 MSA patients were accurately classified. Formation of the decision tree using these parameters was both descriptive and predictive in differentiating between MSA and PD. • Parkinson's disease and multiple system atrophy can be distinguished on MR imaging. • Combined conventional MRI and diffusion tensor imaging improves the accuracy of diagnosis. • A decision tree is descriptive and predictive in differentiating between clinical entities. • A decision tree can reliably differentiate Parkinson's disease from multiple system atrophy.

Brain response to images of food varying in energy density is associated with body composition in 7- to 10-year-old children: Results of an exploratory study.

Science.gov (United States)

Fearnbach, S Nicole; English, Laural K; Lasschuijt, Marlou; Wilson, Stephen J; Savage, Jennifer S; Fisher, Jennifer O; Rolls, Barbara J; Keller, Kathleen L

2016-08-01

Energy balance is regulated by a multifaceted system of physiological signals that influence energy intake and expenditure. Therefore, variability in the brain's response to food may be partially explained by differences in levels of metabolically active tissues throughout the body, including fat-free mass (FFM) and fat mass (FM). The purpose of this study was to test the hypothesis that children's body composition would be related to their brain response to food images varying in energy density (ED), a measure of energy content per weight of food. Functional magnetic resonance imaging (fMRI) was used to measure brain response to High (>1.5kcal/g) and Low (vs. Low ED) in a priori defined brain regions of interest previously implicated in energy homeostasis and reward processing. Pearson's correlations were then calculated between activation in these regions for various contrasts (High ED-Low ED, High ED-Control, Low ED-Control) and child body composition (FFM index, FM index, % body fat). Relative to Low ED foods, High ED foods elicited greater BOLD activation in the left thalamus. In the right substantia nigra, BOLD activation for the contrast of High ED-Low ED foods was positively associated with child FFM. There were no significant results for the High ED-Control or Low ED-Control contrasts. Our findings support literature on FFM as an appetitive driver, such that greater amounts of lean mass were associated with greater activation for High ED foods in an area of the brain associated with dopamine signaling and reward (substantia nigra). These results confirm our hypothesis that brain response to foods varying in energy content is related to measures of child body composition. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemotaxonomic significance of the terpene composition in natural populations of Pinus nigra J.F.Arnold from Serbia.

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Sarac, Zorica; Bojović, Srdjan; Nikolić, Biljana; Tešević, Vele; Ethorđević, Iris; Marin, Petar D

2013-08-01

The essential-oil variability in seven native populations belonging to different infraspecific taxa of Pinus nigra (ssp. nigra, var. gocensis, ssp. pallasiana, and var. banatica) growing wild in Serbia was analyzed. In the needles of 195 trees from seven populations, 58 essential-oil components were identified. The major components were α-pinene (43.6%) and germacrene D (29.8%), comprising together 73.4% of the total oil composition. Based on the average chemical profile of the main terpene components (with contents >5%), the studied populations were found to be the most similar to populations from central Italy and Greece (ssp. nigra). Cluster analysis showed the division of the populations into three principal groups: the first group consisted of Populations I, II, III, IV, and V (considered as ssp. nigra group), the second of Population VI (ssp. pallasiana group), and the third of Population VII, which had the most distinct oil composition (ssp. banatica group). The taxonomic implications of the essential-oil profiles of the investigated taxa of this very complex species are discussed. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

Intra- and interpopulation relationships and taxonomic status of Pinus nigra Arnold in Croatia according to morphology and anatomy of needles

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Zlatko Liber

2014-01-01

Full Text Available Intra- and interpopulational relationships and taxonomic status of six natural black pine populations (Pinus nigra Arnold from Croatia were analyzed. Special attention in this research was paid to the establishment of taxonomic status and distribution of stenoendemic Dalmatian black pine (Pinus nigra Arnold subsp. dalmatica (Vis. Franco. Three morphological and twenty-one anatomical traits of needles were used as well as analysis by the methods of multivariate statistics. Most of the researched individuals showed strong population affiliation, whereas a clinal transition of morphological and anatomical traits of needles was determined among the populations. The opinion of the existence of three subspecies of black pine on the territory of Republic of Croatia (Pinus nigra Arnold subsp. nigra, Pinus nigra Arnold subsp. dalmatica (Vis. Franco and Pinus nigra Arnold subsp. illyrica (Vid. Fukarek was confirmed. For each of the three subspecies new ranges were represented. Four Croatian populations were included in the stenoendemic subspecies of the Dalmatian black pine (Brač, Hvar, Grobnik and Pelješac, and a new distribution, broken in two, was suggested. Since the Dalmatian black pine has been reduced to several populations only, and there are some signs of continuous diminishing of its range, this research points out the need of making an action plan to preserve all natural populations of this subspecies.

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...

Antiproliferative and apoptotic effect of Morus nigra extract on human prostate cancer cells

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Ibrahim Turan

2017-02-01

Full Text Available Background: Morus nigra L. belongs to the family Moraceae and is frequently used in traditional medicine. Numerous studies have investigated the antiproliferative effects of various extracts of different Morus species, but studies involving the in vitro cytotoxic effect of M. nigra extract are very limited. The purpose of this study was to evaluate the phenolic composition and antioxidant activity of dimethyl sulfoxide extract of M. nigra (DEM and to investigate, for the first time, the probable cytotoxic effect in human prostate adenocarcinoma (PC-3 cells together with the mechanism involved. Methods: Total polyphenolic contents (TPC, ferric reducing antioxidant power (FRAP and phenolic compounds of DEM were evaluated using spectrophotometric procedures and HPLC. The cytotoxic effect of DEM on PC-3 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic effect of DEM on PC-3 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, while caspase activity was investigated using luminometric analysis. Results: TPC and FRAP values were 20.7 ± 0.3 mg gallic acid equivalents and 48.8 ± 1.6 mg trolox equivalents per g sample, respectively. Ascorbic acid and chlorogenic acid were the major phenolic compounds detected at HPLC analysis. DEM arrested the cell cycle of PC-3 cells at the G1 phase, induced apoptosis via increased caspase activity and reduced mitochondrial membrane potential. Conclusions: Our results indicate that M. nigra may be a novel candidate for the development of new natural product based therapeutic agents against prostate cancer.

Pinus nigra and Pinus pinaster needles as passive samplers of polycyclic aromatic hydrocarbons

International Nuclear Information System (INIS)

Piccardo, Maria Teresa; Pala, Mauro; Bonaccurso, Bruna; Stella, Anna; Redaelli, Anna; Paola, Gaudenzio; Valerio, Federico

2005-01-01

Nine polycyclic aromatic hydrocarbons (PAHs) were analysed in pine needles of different ages (from 6 to 30 months) collected from two species, Pinus nigra and Pinus pinaster, in seven sites located along a transect from a suburban to a rural area of Genoa (Italy). In all sites and for both species, concentrations of more volatile PAHs (phenanthrene, anthracene, fluoranthene, pyrene) were higher than those for other less volatile PAHs, which are preferentially sorbed to airborne particulates (benzo[a]anthracene, chrysene, benzofluoranthenes, benzo[a]pyrene). Concentrations of total PAHs found in P. nigra in the rural sites were, on the average, 2.3 times higher than those in P. pinaster growing nearby. In both pine species, concentrations of volatile PAHs increased according to needle age. Annual trends of other PAHs were more variable, with a general decrease in older needles. P. pinaster needles are shown to be more reliable passive samplers, since they are more resistant to plant diseases, and considerable variation in PAH concentration was observed in P. nigra needles with moulds and fungi. - The suitability of the pine needles as passive air samplers for persistent trace organics is demonstrated

Pinus nigra and Pinus pinaster needles as passive samplers of polycyclic aromatic hydrocarbons

Energy Technology Data Exchange (ETDEWEB)

Piccardo, Maria Teresa [Environmental Chemistry Laboratory, National Cancer Research Institute, Genova. L.go Rosanna Benzi n. 10, 16132 Genova (Italy)]. E-mail: chimamb@istge.it; Pala, Mauro [Environmental Chemistry Laboratory, National Cancer Research Institute, Genova. L.go Rosanna Benzi n. 10, 16132 Genova (Italy); Bonaccurso, Bruna [Environmental Chemistry Laboratory, National Cancer Research Institute, Genova. L.go Rosanna Benzi n. 10, 16132 Genova (Italy); Stella, Anna [Environmental Chemistry Laboratory, National Cancer Research Institute, Genova. L.go Rosanna Benzi n. 10, 16132 Genova (Italy); Redaelli, Anna [Environmental Chemistry Laboratory, National Cancer Research Institute, Genova. L.go Rosanna Benzi n. 10, 16132 Genova (Italy); Paola, Gaudenzio [Botany Department, Genoa University, C.so Dogali 1 canc., 16136 Genova (Italy); Valerio, Federico [Environmental Chemistry Laboratory, National Cancer Research Institute, Genova. L.go Rosanna Benzi n. 10, 16132 Genova (Italy)

2005-01-01

Nine polycyclic aromatic hydrocarbons (PAHs) were analysed in pine needles of different ages (from 6 to 30 months) collected from two species, Pinus nigra and Pinus pinaster, in seven sites located along a transect from a suburban to a rural area of Genoa (Italy). In all sites and for both species, concentrations of more volatile PAHs (phenanthrene, anthracene, fluoranthene, pyrene) were higher than those for other less volatile PAHs, which are preferentially sorbed to airborne particulates (benzo[a]anthracene, chrysene, benzofluoranthenes, benzo[a]pyrene). Concentrations of total PAHs found in P. nigra in the rural sites were, on the average, 2.3 times higher than those in P. pinaster growing nearby. In both pine species, concentrations of volatile PAHs increased according to needle age. Annual trends of other PAHs were more variable, with a general decrease in older needles. P. pinaster needles are shown to be more reliable passive samplers, since they are more resistant to plant diseases, and considerable variation in PAH concentration was observed in P. nigra needles with moulds and fungi. - The suitability of the pine needles as passive air samplers for persistent trace organics is demonstrated.

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

International Nuclear Information System (INIS)

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)

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

Energy Technology Data Exchange (ETDEWEB)

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.

Composition of the essential oils of Pinus nigra Arnold from Turkey

OpenAIRE

Turkey, Composition of the essential oils of Pin

2010-01-01

Essential oil composition of the needles of Pinus nigra Arnold collected from different localities in Turkey was investigated by GC and GC/MS. The main components in the oils were a-pinene, b-pinene, b-caryophyllene, and germacrene D.

Composition of the essential oils of Pinus nigra Arnold from Turkey

OpenAIRE

Turkey, Composition of the essential oils of Pin; SEZİK, Ekrem; ÜSTÜN, Osman; DEMİRCİ, Betül; BAŞER, K. Hüsnü Can

2014-01-01

Essential oil composition of the needles of Pinus nigra Arnold collected from different localities in Turkey was investigated by GC and GC/MS. The main components in the oils were a-pinene, b-pinene, b-caryophyllene, and germacrene D.

ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

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Daniel Komnig

Full Text Available Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC. Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

[Motivation and Emotional States: Structural Systemic, Neurochemical, Molecular and Cellular Mechanisms].

Science.gov (United States)

Bazyan, A S

2016-01-01

The structural, systemic, neurochemical, molecular and cellular mechanisms of organization and coding motivation and emotional states are describe. The GABA and glutamatergic synaptic systems of basal ganglia form a neural network and participate in the implementation of voluntary behavior. Neuropeptides, neurohormones and paracrine neuromodulators involved in the organization of motivation and emotional states, integrated with synaptic systems, controlled by neural networks and organizing goal-directed behavior. Structural centers for united and integrated of information in voluntary and goal-directed behavior are globus pallidus. Substantia nigra pars reticulata switches the information from corticobasal networks to thalamocortical networks, induces global dopaminergic (DA) signal and organize interaction of mesolimbic and nigostriatnoy DA systems controlled by prefrontal and motor cortex. Together with the motor cortex, substantia nigra displays information in the brainstem and spinal cord to implementation of behavior. Motivation states are formed in the interaction of neurohormonal and neuropeptide systems by monoaminergic systems of brain. Emotional states are formed by monoaminergic systems of the mid-brain, where the leading role belongs to the mesolimbic DA system. The emotional and motivation state of the encoded specific epigenetic molecular and chemical pattern of neuron.

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.

MIDBRAIN CATECHOLAMINERGIC NEURONS CO-EXPRESS α-SYNUCLEIN AND TAU IN PROGRESSIVE SUPRANUCLEAR PALSY

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María Elena eErro Aguirre

2015-03-01

Full Text Available Objective: To analyze the frequency and distribution of α-synuclein deposits in progressive supranuclear palsy (PSP.Methods: The brains of 25 cases of pathologically confirmed PSP were evaluated with immunohistochemistry for α-synuclein and tau. Multiple immunofluorescent stains were applied to analyze the expression of tau and α-synuclein aggregates in catecholaminergic neurons. Patients’ clinical symptoms were retrospectively recorded. Results: Deposits α-synuclein in the form of typical Lewy bodies (LBs were only found in two PSP cases (8% that fulfilled the clinical subtype of PSP known as Richardson’s syndrome (RS. LBs were present in the locus ceruleus, substantia nigra pars compacta, basal forebrain, amygdala and cingulated cortex in a distribution mimicking that of Parkinson’s disease. Triple-immunolabeling revealed co-expression of α-synuclein and tau proteins in some tyrosine hydroxilase-positive neurons of the locus ceruleus and substantia nigra pars compacta.Conclusions: There is no apparent clinical correlation between the presence of LBs in PSP. Tau protein co-aggregate with α-synuclein in catecholaminergic neurons of PSP brains suggesting a synergistic interaction between the two proteins. This is in keeping with the current view of neurodegenerative disorders as ‘misfolded protein diseases’.

Shifted dynamic interactions between subcortical nuclei and inferior frontal gyri during response preparation in persistent developmental stuttering.

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Metzger, F Luise; Auer, Tibor; Helms, Gunther; Paulus, Walter; Frahm, Jens; Sommer, Martin; Neef, Nicole E

2018-01-01

Persistent developmental stuttering is associated with basal ganglia dysfunction or dopamine dysregulation. Here, we studied whole-brain functional connectivity to test how basal ganglia structures coordinate and reorganize sensorimotor brain networks in stuttering. To this end, adults who stutter and fluent speakers (control participants) performed a response anticipation paradigm in the MRI scanner. The preparation of a manual Go/No-Go response reliably produced activity in the basal ganglia and thalamus and particularly in the substantia nigra. Strikingly, in adults who stutter, substantia nigra activity correlated positively with stuttering severity. Furthermore, functional connectivity analyses yielded altered task-related network formations in adults who stutter compared to fluent speakers. Specifically, in adults who stutter, the globus pallidus and the thalamus showed increased network synchronization with the inferior frontal gyrus. This implies dynamic shifts in the response preparation-related network organization through the basal ganglia in the context of a non-speech motor task in stuttering. Here we discuss current findings in the traditional framework of how D1 and D2 receptor activity shapes focused movement selection, thereby suggesting a disproportional involvement of the direct and the indirect pathway in stuttering.

Standards in neurosonology. Part I

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Joanna Wojcza

2015-09-01

Full Text Available The paper presents standards related to ultrasound imaging of the cerebral vasculature and structures. The aim of this paper is to standardize both the performance and description of ultrasound imaging of the extracranial and intracranial cerebral arteries as well as a study of a specifi c brain structure, i.e. substantia nigra hyperechogenicity. The following aspects are included in the description of standards for each ultrasonographic method: equipment requirements, patient preparation, study technique and documentation as well as the required elements of ultrasound description. Practical criteria for the diagnosis of certain pathologies in accordance with the latest literature were also presented. Furthermore, additional comments were included in some of the sections. Part I discusses standards for the performance, documentation and description of different ultrasound methods (Duplex, Doppler. Part II and III are devoted to standards for specifi c clinical situations (vasospasm, monitoring after the acute stage of stroke, detection of a right-toleft shunts, confi rmation of the arrest of the cerebral circulation, an assessment of the functional effi ciency of circle of Willis, an assessment of the cerebrovascular vasomotor reserve as well as the measurement of substantia nigra hyperechogenicity.

Standards in neurosonology. Part III

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Joanna Wojczal

2016-06-01

Full Text Available The paper presents standards related to ultrasound imaging of the cerebral vasculature and structures. The aim of this paper is to standardize both the performance and description of ultrasound imaging of the extracranial and intracranial cerebral arteries as well as a study of a specific brain structure, i.e. substantia nigra hyperechogenicity. The following aspects are included in the description of standards for each ultrasonographic method: equipment requirements, patient preparation, study technique and documentation as well as the required elements of ultrasound description. Practical criteria for the diagnosis of certain pathologies in accordance with the latest literature were also presented. Furthermore, additional comments were included in some of the sections. Part I discusses standards for the performance, documentation and description of different ultrasound methods (Duplex, Doppler. Part II and III are devoted to standards for specific clinical situations (vasospasm, monitoring after the acute stage of stroke, detection of a right-to-left shunts, confirmation of the arrest of the cerebral circulation, an assessment of the functional efficiency of circle of Willis, an assessment of the cerebrovascular vasomotor reserve as well as the measurement of substantia nigra hyperechogenicity.

In vitro antimicrobial and antiprotozoal activities, phytochemical screening and heavy metals toxicity of different parts of Ballota nigra.

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Ullah, Najeeb; Ahmad, Ijaz; Ayaz, Sultan

2014-01-01

The study was done to assess the phytochemicals (flavonoids, terpenoids, saponins, tannin, alkaloids, and phenol) in different parts (root, stem, and leaves) of Ballota nigra and correlated it to inhibition of microbes (bacteria and fungi), protozoan (Leishmania), and heavy metals toxicity evaluation. In root and stem flavonoids, terpenes and phenols were present in ethanol, chloroform, and ethyl acetate soluble fraction; these were found to be the most active inhibiting fractions against all the tested strains of bacteria, fungi, and leishmania. While in leaves flavonoids, terpenes, and phenols were present in ethanol, chloroform, and n-butanol fractions which were the most active fractions against both types of microbes and protozoan (leishmania) in in vitro study. Ethanol and chloroform fractions show maximum inhibition against Escherichia coli (17 mm). The phytochemical and biological screenings were correlated with the presence of heavy metals in selected plant Ballota nigra. Cr was found above permissible value (above 1.5 mg/kg) in all parts of the plant. Ni was above WHO limit in B. nigra root and leaves (3.35 ± 1.20 mg/kg and 5.09 ± 0.47 mg/kg, respectively). Fe was above permissible value in all parts of B. nigra (above 20 mg/kg). Cd was above permissible value in all parts of the plant (above 0.3 mg/kg). Pb was above WHO limit (above 2 mg/kg) in all parts of Ballota nigra.

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

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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

Lead tolerance of Populus nigra in symbiosis with arbuscular mycorrhizal fungi in relation to physiological parameters

International Nuclear Information System (INIS)

Salehi, A.; Tabari, M.; Mohammadi Goltapeh, E.; Shirvani, A.

2016-01-01

With the aim to examine lead tolerance of Populus nigra (clone 62/154) in symbiosis witharbuscular mycorrhizal fungi, a greenhouse experiment was carried out in a factorial randomized complete scheme with two factors 1) fungal inoculation in 4 levels (control, inoculation with Glomus mosseae, inoculation with G. intraradices and inoculation with G. mosseae+G. intraradices) and 2) lead in 4 levels (0, 100, 500 and 1000 mg kg-1 soil). Mycorrhizal colonization and physiological parameters of plants were measured at the end of growth season. Results showed that at all Pb levels, the percentage of root mycorrhizal colonization in fungal treatments was significantly higher than that in control treatment (without fungal inoculation), however without significant differences between 3 fungal treatments. Pb treatments had no significant effect on root mycorrhizal colonization of P. nigra plants. Also, photosynthesis, stomatal conductance, transpiration, intercellular CO2 concentration and water use efficiency of P. nigra plants had no significant inhibitory effects versus the control found under Pb and fungal treatments or their interaction.The results of present study demonstrated that fungal treatments had no significant effects on physiological parameters and Pb tolerance of P. nigraplants. While, in relation to mycorrhizal colonization and physiological parameters, P. nigra clone 62/154 showeda good tolerance to Pb stress. So, in further investigations of phytoremediation of lead-contaminated soils, this clone can be considered as a proposed species.

Protective Mechanisms of Nitrone Antioxidants in Kanic Acid Induced Neurodegeneration

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2004-01-01

Shin, E.J., Suh, J.H., Floyd, R.A., Bing, G. (1999) Protection of methamphetamine nigrostriatal toxicity by dietary selenium. Brain Res. 851:76-86...HC, and Bing, GY. (2004) Interleukin-10 protects against lipopolysaccharide-mediated neurotoxicity in substantia nigra Neurosci. Abstr. 29:677.18. 71...2004) Roles of the cyclooxygenase-2 and oxidative stress in the methamphetamine - induced neurotoxicity Neurosci. Abstr. 29:235.4.

Manganese Research Health Project (MHRP)

Science.gov (United States)

2009-02-01

green nucleic acid staining further confirmed the neurotoxic effect of cadmium in this cell model (Fig 10C). Next, we examined the enzymatic activity...Quantification of Nissl bodies revealed a widespread reduction in SNpc cell numbers. Other areas of the basal ganglia were also altered by manganese as...the substantia nigra pars compacta (SNpc) following manganese treatment. Quantification of Nissl bodies revealed a widespread reduction in SNpc

Temperature as an ecological factor in the distribution of two closely related freshwater Triclads: an experimental study. [Polycelis tenuis, polycelis nigra

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Lascombe, C.; Pattee, E.; Bornard, C.

1975-01-01

The influence of temperature on the ecophysiology of two closely related limnophilic Triclads, Polycelis tenuis and P. nigra, in the Lyons region was investigated. Both species have the same physiological rate in the middle zone of the temperature range, but P. tenuis prevails at both ends of the range. It tolerates higher temperatures and its reproduction rate is greater in the cold. Also, because of the existence of physiological races, it seems adapted to a greater diversity of situations. It appears as a real eurytherm. These different points contribute to the explanation of the habitat of both species in the region.

A neurocomputational account of reward and novelty processing and effects of psychostimulants in attention deficit hyperactivity disorder.

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Sethi, Arjun; Voon, Valerie; Critchley, Hugo D; Cercignani, Mara; Harrison, Neil A

2018-05-01

Computational models of reinforcement learning have helped dissect discrete components of reward-related function and characterize neurocognitive deficits in psychiatric illnesses. Stimulus novelty biases decision-making, even when unrelated to choice outcome, acting as if possessing intrinsic reward value to guide decisions toward uncertain options. Heightened novelty seeking is characteristic of attention deficit hyperactivity disorder, yet how this influences reward-related decision-making is computationally encoded, or is altered by stimulant medication, is currently uncertain. Here we used an established reinforcement-learning task to model effects of novelty on reward-related behaviour during functional MRI in 30 adults with attention deficit hyperactivity disorder and 30 age-, sex- and IQ-matched control subjects. Each participant was tested on two separate occasions, once ON and once OFF stimulant medication. OFF medication, patients with attention deficit hyperactivity disorder showed significantly impaired task performance (P = 0.027), and greater selection of novel options (P = 0.004). Moreover, persistence in selecting novel options predicted impaired task performance (P = 0.025). These behavioural deficits were accompanied by a significantly lower learning rate (P = 0.011) and heightened novelty signalling within the substantia nigra/ventral tegmental area (family-wise error corrected P attention deficit hyperactivity disorder participants' overall task performance (P = 0.011), increased reward-learning rates (P = 0.046) and enhanced their ability to differentiate optimal from non-optimal novel choices (P = 0.032). It also reduced substantia nigra/ventral tegmental area responses to novelty. Preliminary cross-sectional evidence additionally suggested an association between long-term stimulant treatment and a reduction in the rewarding value of novelty. These data suggest that aberrant substantia nigra/ventral tegmental area novelty processing plays an

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

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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

Wood identification of Dalbergia nigra (CITES Appendix I) using quantitative wood anatomy, principal components analysis and naïve Bayes classification

Science.gov (United States)

Gasson, Peter; Miller, Regis; Stekel, Dov J.; Whinder, Frances; Ziemińska, Kasia

2010-01-01

Background and Aims Dalbergia nigra is one of the most valuable timber species of its genus, having been traded for over 300 years. Due to over-exploitation it is facing extinction and trade has been banned under CITES Appendix I since 1992. Current methods, primarily comparative wood anatomy, are inadequate for conclusive species identification. This study aims to find a set of anatomical characters that distinguish the wood of D. nigra from other commercially important species of Dalbergia from Latin America. Methods Qualitative and quantitative wood anatomy, principal components analysis and naïve Bayes classification were conducted on 43 specimens of Dalbergia, eight D. nigra and 35 from six other Latin American species. Key Results Dalbergia cearensis and D. miscolobium can be distinguished from D. nigra on the basis of vessel frequency for the former, and ray frequency for the latter. Principal components analysis was unable to provide any further basis for separating the species. Naïve Bayes classification using the four characters: minimum vessel diameter; frequency of solitary vessels; mean ray width; and frequency of axially fused rays, classified all eight D. nigra correctly with no false negatives, but there was a false positive rate of 36·36 %. Conclusions Wood anatomy alone cannot distinguish D. nigra from all other commercially important Dalbergia species likely to be encountered by customs officials, but can be used to reduce the number of specimens that would need further study. PMID:19884155

Conducta alimenticia, supervivencia y crecimiento de juveniles silvestres de Graus nigra Philippi, 1887 en cautiverio (Perciformes: Kyphosidae Feeding behavior, survival, and growth of wild Graus nigra Philippi, 1887 juveniles in captivity (Perciformes: Kyphosidae

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Héctor Flores

2011-11-01

Full Text Available Se colectaron juveniles silvestres de Graus nigra, que fueron aclimatados durante 30 días en estanques con flujo de agua abierto y a temperatura ambiente, siendo alimentados con alimento formulado. Los peces fueron separados en seis grupos que se mantuvieron en experimentación por 196 días. La supervivencia promedio fue de 80%. El crecimiento en longitud total mostró un incremento promedio del 93,3% para los juveniles grandes (grupos 4, 5 y 6 y 125% para los pequeños (grupos 1, 2 y 3. El crecimiento en peso total mostró un incremento promedio de 434% para los peces grandes (grupos 4, 5 y 6 y de 707% para los pequeños (grupos 1, 2 y 3. Se concluyó que G. nigra toleró el cautiverio y el manejo, con una supervivencia relativamente alta, lo que hace de ella una especie atractiva para la acuicultura chilena.Wild juveniles of Graus nigra were collected and acclimated for 30 days in ponds with open-water flow and ambient temperature; the specimens were given a formulated feed. Fish individuals were separated into six groups that were studied for 196 days. The average survival was 80%. The total length increased an average of 93.3% for large individuals (groups 4, 5, 6 and 125% for small ones (groups 1, 2, 3. The total weight showed an average increase of 434% for large fishes (groups 4, 5, 6 and 707% for small ones (groups 1, 2, 3. Graus nigra was found to tolerate captivity and handling, with a relatively high survival rate, making it an attractive species for aquaculture in Chile.

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

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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.

Effect of ovarian tissue storage in Morus nigra extract on the morphology and DNA fragmentation of ovine preantral follicles

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Agnes Yasmin Pitombeira Cavalcante

2017-08-01

Full Text Available This study demonstrated the effect of Morus nigra leaf extract during ovine ovarian tissue transportation on the survival and apoptosis of preantral follicles in vitro. High Performance Liquid Chromatography (HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract. Four pairs of ovaries from four sheep were collected. The ovarian cortex was fragmented and one fragment was fixed in 10% buffered formaldehyde and processed for histological and TUNEL analysis (fresh control. The other fragments were placed in Minimal Essential Medium (MEM – control medium or M. nigra extract (0.025; 0.05 or 0.1 mg/mL and stored (simulating transport at 4ºC for 6, 12 or 24 h. Preserved fragments (6 h were also destined to histological and TUNEL analysis. HPLC analysis confirmed the presence of antioxidant compounds (rutin, isoquercetin e kaempferitrin in the extract. There was a decrease (P 0.05 to 0.1 mg/mL of the extract. Apoptosis increased (P < 0.05 after conservation for 6 h in all treatments compared to the fresh control. Moreover, TUNEL positive cells decreased (P < 0.05 after preservation in 0.05 or 0.1 mg/mL M. nigra compared to MEM or 0.025 mg/mL M. nigra. In conclusion, 0.05 mg/mL M. nigra extract can be used as a preservation medium for ovine ovarian tissue at 4°C for up to 6 h.

Distribution of Wfs1 protein in the central nervous system of the mouse and its relation to clinical symptoms of the Wolfram syndrome

DEFF Research Database (Denmark)

Luuk, H.; Koks, S.; Plaas, M.

2008-01-01

enrichment of Wf1 protein in the central extended amygdala and ventral striatum. Prominent Wfs1 expression was seen in the hippocampal CA1 region, parasubiculum, superficial part of the second and third layers of the prefrontal cortex and proisocortical areas, hypothalamic magnocellular neurosecretory system......, alveus, fimbria, dorsal hippocampal commissure; subiculum, and to a lesser extent in the central sublenticular extended amygdala, compact part of substantia nigra, and ventral tegmental area. The neuroanatomical findings suggest that the lack of Wf1 protein function can be related to several neurological...... and psychiatric symptoms found in Wolfram syndrome. Enrichment of Wfs1 protein in the central extended amygdala suggests a role in the modulation of anxiety and fear Udgivelsesdato: 2008/8/20...

Abnormal chloride homeostasis in the substancia nigra pars reticulata contributes to locomotor deficiency in a model of acute liver injury.

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Yan-Ling Yang

Full Text Available BACKGROUND: Altered chloride homeostasis has been thought to be a risk factor for several brain disorders, while less attention has been paid to its role in liver disease. We aimed to analyze the involvement and possible mechanisms of altered chloride homeostasis of GABAergic neurons within the substantia nigra pars reticulata (SNr in the motor deficit observed in a model of encephalopathy caused by acute liver failure, by using glutamic acid decarboxylase 67 - green fluorescent protein knock-in transgenic mice. METHODS: Alterations in intracellular chloride concentration in GABAergic neurons within the SNr and changes in the expression of two dominant chloride homeostasis-regulating genes, KCC2 and NKCC1, were evaluated in mice with hypolocomotion due to hepatic encephalopathy (HE. The effects of pharmacological blockade and/or activation of KCC2 and NKCC1 functions with their specific inhibitors and/or activators on the motor activity were assessed. RESULTS: In our mouse model of acute liver injury, chloride imaging indicated an increase in local intracellular chloride concentration in SNr GABAergic neurons. In addition, the mRNA and protein levels of KCC2 were reduced, particularly on neuronal cell membranes; in contrast, NKCC1 expression remained unaffected. Furthermore, blockage of KCC2 reduced motor activity in the normal mice and led to a further deteriorated hypolocomotion in HE mice. Blockade of NKCC1 was not able to normalize motor activity in mice with liver failure. CONCLUSION: Our data suggest that altered chloride homeostasis is likely involved in the pathophysiology of hypolocomotion following HE. Drugs aimed at restoring normal chloride homeostasis would be a potential treatment for hepatic failure.

Reproductive biology and food habits of Pseudoboa nigra (Serpentes: Dipsadidae from the Brazilian cerrado

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Renata de Paula Orofino

2010-07-01

Full Text Available Herein we provide data on body size, sexual size dimorphism,reproductive cycle, and food habits of the pseudoboini snake Pseudoboa nigra, which is distributed mainly in central South America throughout the Cerrado domain. Based on dissections of 147 preserved specimens, it is shown that females attain, and mature at,larger body sizes than males. There is no significant sexual dimorphism in head length, but males have longer tails relative to their body sizes. Vitellogenesis, egg-laying, and sperm production occur throughout the year, but males do not exhibit long-term sperm storage. The main prey of P. nigra is lizards; there is no evidence of ontogenetic change or sex differences in the diet of this species.

Determination of Antioxidant Activity and Toxicity of Sambucus nigra Fruit Extract Using Alternative Methods

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Elena Doroftei

2012-01-01

Full Text Available The aim of the study is to measure the in vitro antioxidant activity of elderberry (Sambucus nigra fruit extract and to study its toxicity in a plant model system with regard to its possible application in food and agricultural industry. The antioxidant capacity of Sambucus nigra fruit powder was quantified by a photochemiluminescence method. The study of phytotoxicity of aqueous solutions of powder extract was performed using Allium cepa as a test organism. Photochemiluminescence determinations showed a very high antioxidant capacity of the product but also revealed its cytotoxic effect, along with mitodepressive activity and even inhibiton of mitosis at the preprophase stage when the fruit extract was used at higher concentrations. Aqueous solutions of the fruit powder have a reasonably expressed mutagenic activity in vivo on the radicles of Allium cepa, especially when they are used at a concentration of 1 g/dL for a prolonged time (48 h. At lower concentrations (0.1 g/dL, however, the mutagenic effect was not observed any more. The conclusion of our study is that Sambucus nigra fruit extract powder has a very high in vitro antioxidant activity and no mutagenic effects at low concentrations, which makes it recommendable for applications in the food industry.

Canopy treatment influences growth of replacement tree species in Fraxinus nigra forests threatened by the emerald ash borer in Minnesota, USA

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Christopher E. Looney; Anthony W. D' Amato; Brian J. Palik; Robert A. Slesak

2017-01-01

Fraxinus nigra Marsh. (black ash), a dominant tree species of wetland forests in northern Minnesota, USA, is imperiled by the invasive insect emerald ash borer (EAB; Agrilus planipennis Fairmaire, 1888). Regeneration of associated tree species is generally low in F. nigra forests and could be impacted...

Exercise Does Not Protect against MPTP-Induced Neurotoxicity in BDNF Happloinsufficent Mice

OpenAIRE

Gerecke, Kim M.; Jiao, Yun; Pagala, Viswajeeth; Smeyne, Richard J.

2012-01-01

Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN) dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF), have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is depende...

The distribution of multiple opiate receptors in bovine brain

International Nuclear Information System (INIS)

Ninkovic, M.; Hunt, S.P.; Emson, P.C.; Iversen, L.L.

1981-01-01

The distribution of μ and delta opiate receptors in bovine brain has been investigated using the selective radioligands [ 3 H]morphine and D-[ 3 H]Ala 2 , D-Leu 5 -enkephalin. Their distributions were found to vary independently through different brain areas with up to a 10-fold difference between the ratio of μ to delta binding sites for the substantia nigra and the dentate gyrus of the hippocampus. (Auth.)

Resveratrol attenuates oxidative stress and improves behaviour in 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) challenged mice

OpenAIRE

Anandhan, Annadurai; Tamilselvam, Kuppusamy; Vijayraja, Dhanraj; Ashokkumar, Nataraj; Rajasankar, Srinivasagam; Manivasagam, Thamilarasan

2010-01-01

Background Parkinson's disease (PD) is the most common neurodegenerative disorder, characterized by loss of dopaminergic neurons in substantia nigra and depletion of dopamine in striatum due to mitochondrial dysfunction, oxidative stress, excitotoxicity, apoptosis, inflammation and proteasome failure. Purpose The present study deals with the neuroprotective effect of resveratrol, a wine polyphenol (50 mg/kg body weight) against MPTP (30mg/kg body weight as i.p. administration) induced mice mo...

123-I ioflupane (Datscan) presynaptic nigrostriatal imaging in patients with movement disorders

International Nuclear Information System (INIS)

Soriano Castrejon, Angel; Garcia Vicente, Ana Maria; Cortes Romera, Montserrat; Rodado Marina, Sonia; Poblete Garcia, Victor Manuel; Ruiz Solis, Sebastian Ruiz; Talavera Rubio, Maria del Prado; Vaamonde Cano, Julia

2005-01-01

123-I Ioflupane (Datscan) presynaptic imaging has been shown to have a significant utility in the assessment of patients with movement disorders 123 I Ioflupane SPECT is able to distinguish between Parkinson's disease (PD) and other forms of parkinsonism without degeneration of the nigrostriatal pathway, including a common movement disorder such as essential tremor, and to assess disease progression in PD and other neuro degenerative disorders involving the substantia nigra. (author)

Trasplante de células naturales "dopaminotróficas" nuevo concepto terapeútico antiparkinsoniano

OpenAIRE

Fernández-Espejo, Emilio; El Banoua, F.; Caraballo, Isidoro; Galán Rodríguez, Beatriz; Flores Cordero, Juan Antonio

2003-01-01

Aim and method. Parkinson's disease is caused by the degeneration of dopamineric neurons of substantia nigra projecting to striatum. Cellular substitution represents a potentially treatment once beneficial levodopa effects wear off. A promising therapeutic approach is grafting cells or other vectors which release neuroprotective molecules that stimulate regeneration in the damaged nigrostriatal system or, in other words, that exert a dopaminotrophic action. We have tested the suitability of i...

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...

Impact mortality of black storks (Ciconia nigra) on medium-voltage overhead power lines in Rheinland-Pfalz; Anflugverluste von Schwarzstoerchen (Ciconia nigra) an Mittelspannungsfreileitungen in Rheinland-Pfalz

Energy Technology Data Exchange (ETDEWEB)

Hormann, M.; Richarz, K. [Staatliche Vogelschutzwarte fuer Hessen, Rheinland-Pfalz und Saarland, Frankfurt am Main (Germany)

1997-12-01

The small breeding population of black storks (Ciconia nigra), which had been growing steadily since first nesting in Rhineland-Palantinate in 1982, has been observably decreasing again since 1993, particularly in its main territories. The high mortality of, for the most part, juvenile black storks resulting from collision with a overhead power line (OHL) is described (30 collision victims since the mid-1980s). The energy utilities are called upon to install underground cables on the relevant sections of the power lines in addition to modifying hazardous types of towers in order to reduce the high bird mortality rate. (orig.) [Deutsch] Fuer den seit einer Erstbrut 1982 in Rheinland-Pfalz stetig angestiegenen kleinen Brutbestand des Schwarzstorchs (Ciconia nigra) sind vor allem in seinen Kerngebieten seit 1993 wieder Bestandsrueckgaenge zu verzeichnen. Die hohen Verluste ueberwiegend junger Schwarzstoerche durch Anflug an Mittel- und Niederspannungsfreileitungen (seit Mitte der 80er Jahre 30 Schwarzstoerche als Anflugopfer) werden beschrieben. Neben der Entschaerfung gefaehrlicher Masttypen wird zur Vermeidung der hohen Anflugverluste eine Erdverkabelung der kritischen Leitungsabschnitte gefordert. (orig.)

Mimetic Muscles in a Despotic Macaque (Macaca mulatta) Differ from Those in a Closely Related Tolerant Macaque (M. nigra).

Science.gov (United States)

Burrows, Anne M; Waller, Bridget M; Micheletta, Jérôme

2016-10-01

Facial displays (or expressions) are a primary means of visual communication among conspecifics in many mammalian orders. Macaques are an ideal model among primates for investigating the co-evolution of facial musculature, facial displays, and social group size/behavior under the umbrella of "ecomorphology". While all macaque species share some social behaviors, dietary, and ecological parameters, they display a range of social dominance styles from despotic to tolerant. A previous study found a larger repertoire of facial displays in tolerant macaque species relative to despotic species. The present study was designed to further explore this finding by comparing the gross morphological features of mimetic muscles between the Sulawesi macaque (Macaca nigra), a tolerant species, and the rhesus macaque (M. mulatta), a despotic species. Five adult M. nigra heads were dissected and mimetic musculature was compared to those from M. mulatta. Results showed that there was general similarity in muscle presence/absence between the species as well as muscle form except for musculature around the external ear. M. mulatta had more musculature around the external ear than M. nigra. In addition, M. nigra lacked a zygomaticus minor while M. mulatta is reported to have one. These morphological differences match behavioral observations documenting a limited range of ear movements used by M. nigra during facial displays. Future studies focusing on a wider phylogenetic range of macaques with varying dominance styles may further elucidate the roles of phylogeny, ecology, and social variables in the evolution of mimetic muscles within Macaca Anat Rec, 299:1317-1324, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Rapid in vitro shoot multiplication of the recalcitrant species Juglans nigra L.

Science.gov (United States)

Micah E. Stevens; Paula M. Pijut

2018-01-01

Black walnut (Juglans nigra L.) has long been prized for its timber, leading to commercial cultivation and significant breeding efforts for improving marketable traits. Vegetative and in vitro black walnut propagation techniques, however, are variable and highly genotype dependent. Optimizing plant growth regulator type and...

Molecular genetic analysis of black poplar (Populus nigra L.) along Dutch rivers

NARCIS (Netherlands)

Arens, P.; Coops, H.; Jansen, J.; Vosman, B.

1998-01-01

The genetic structure of remaining black poplar (Populus nigra) trees on the banks of the Dutch Rhine branches was investigated using the AFLP technique. In total, 143 trees, including one P. deltoides and some P. x euramericana, were analysed using six AFLP primer combinations which generated 319

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.

Neuroprotective and Therapeutic Strategies against Parkinson’s Disease: Recent Perspectives

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Sumit Sarkar

2016-06-01

Full Text Available Parkinsonism is a progressive motor disease that affects 1.5 million Americans and is the second most common neurodegenerative disease after Alzheimer’s. Typical neuropathological features of Parkinson’s disease (PD include degeneration of dopaminergic neurons located in the pars compacta of the substantia nigra that project to the striatum (nigro-striatal pathway and depositions of cytoplasmic fibrillary inclusions (Lewy bodies which contain ubiquitin and α-synuclein. The cardinal motor signs of PD are tremors, rigidity, slow movement (bradykinesia, poor balance, and difficulty in walking (Parkinsonian gait. In addition to motor symptoms, non-motor symptoms that include autonomic and psychiatric as well as cognitive impairments are pressing issues that need to be addressed. Several different mechanisms play an important role in generation of Lewy bodies; endoplasmic reticulum (ER stress induced unfolded proteins, neuroinflammation and eventual loss of dopaminergic neurons in the substantia nigra of mid brain in PD. Moreover, these diverse processes that result in PD make modeling of the disease and evaluation of therapeutics against this devastating disease difficult. Here, we will discuss diverse mechanisms that are involved in PD, neuroprotective and therapeutic strategies currently in clinical trial or in preclinical stages, and impart views about strategies that are promising to mitigate PD pathology.

Calcium Homeostatasis and Mitochondrial Dysfunction in Dopaminergic Neurons of the Substantia Nigra

Science.gov (United States)

2010-03-01

complex I of the electron transport chain (ETC) [18]; this deficit is specific to PD patients [19] and seems to reflect oxidative damage to complex I...to drive pacemaking, SNc DA neurons also engage ion channels that enable Ca2+ to enter the cyto- plasm [36–38], leading to elevated intracellular Ca2...shown schematically are elements of the tricarboxylic acid (TCA) cycle that produces reducing equivalents for the electron transport chain; complexes I

Reproductive characteristics of the Point Arena mountain beaver (Aplodontia rufa nigra)

Science.gov (United States)

William Zielinski; M. J. Mazurek

2016-01-01

Little is known about the ecology and life history of the federally endangered Point Arena mountain beaver (Aplodontia rufa nigra). The distribution of this primitive burrowing rodent is disjunct from the balance of the species’ range and occurs in a unique maritime environment of coastal grasslands and forests. Fundamental to protecting this taxon...

Midbrain Gene Screening Identifies a New Mesoaccumbal Glutamatergic Pathway and a Marker for Dopamine Cells Neuroprotected in Parkinson?s Disease

OpenAIRE

Viereckel, Thomas; Dumas, Sylvie; Smith-Anttila, Casey J. A.; Vlcek, Bianca; Bimpisidis, Zisis; Lagerstr?m, Malin C.; Konradsson-Geuken, ?sa; Wall?n-Mackenzie, ?sa

2016-01-01

The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for ...

Sulfuretin Attenuates MPP+-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways

OpenAIRE

Pariyar, Ramesh; Lamichhane, Ramakanta; Jung, Hyun Ju; Kim, Sung Yeon; Seo, Jungwon

2017-01-01

Parkinson’s disease (PD) is the second most common neurodegenerative disease. It is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress and mitochondrial dysfunction contribute to the loss of dopaminergic neurons in PD. Sulfuretin is a potent antioxidant that is reported to be beneficial in the treatment of neurodegenerative diseases. In this study, we examined the protective effect of sulfuretin against 1-methyl-4-phenyl pyridinium (MPP+)-induc...

The Energy Cost of Action Potential Propagation in Dopamine Neurons: Clues to Susceptibility in Parkinson’s Disease

OpenAIRE

Eleftheria Kyriaki Pissadaki; J. Paul eBolam

2013-01-01

Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson’s disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated, axonal arbor that is orders of magnitude larger than other neuronal types. We suggest that this puts them under such a high energy demand that any stressor that perturbs energy production l...

Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

OpenAIRE

Garcia, Bonnie G.; Neely, M. Diana; Deutch, Ariel Y.

2010-01-01

Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if dec...

Rotenone and paraquat perturb dopamine metabolism: a computational analysis of pesticide toxicity

OpenAIRE

Qi, Zhen; Miller, Gary W.; Voit, Eberhard O.

2013-01-01

Pesticides, such as rotenone and paraquat, are suspected in the pathogenesis of Parkinson’s disease (PD), whose hallmark is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Thus, compounds expected to play a role in the pathogenesis of PD will likely impact the function of dopaminergic neurons. To explore the relationship between pesticide exposure and dopaminergic toxicity, we developed a custom-tailored mathematical model of dopamine metabolism and utilize...

Oxidative stress and Parkinson’s Disease

OpenAIRE

Javier eBlesa; Javier eBlesa; Javier eBlesa; Ines eTrigo-Damas; Ines eTrigo-Damas; Anna eQuiroga-Varela; Vernice Ruffin Jackson-Lewis

2015-01-01

Parkinson disease is a chronic, progressive neurological disease that is associated with a loss of dopaminergic neurons in the substantia nigra of the brain. The molecular mechanisms underlying the loss of these neurons still remain elusive. Oxidative stress is thought to play an important role in dopaminergic neurotoxicity. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neuronal degeneration in Parkinson’s Disease. Environmental factors, such as neuro...

Superoxide radical dismutation as protective mechanism to hamper the progression of Parkinson's disease

OpenAIRE

Filograna, Roberta

2015-01-01

Abstract Parkinson's disease (PD) is a degenerative neurological syndrome characterized by the preferential loss of dopaminergic (DAergic) neurons in the Substantia Nigra pars compacta. PD is still incurable and conventional therapies treat only symptoms to improve the quality of life. Therefore, there is a impelling need to find out new therapeutic strategies that not only provide symptomatic relief but also halt or reverse the neuronal damage hampering PD progression. Even though the pat...

Accurate counting of neurons in frozen sections: some necessary precautions.

OpenAIRE

Cooper, J D; Payne, J N; Horobin, R W

1988-01-01

In 30 microns frozen sections of rat midbrain the retrograde axonal transport of diamidino yellow, a fluorescent tracer, was used to demonstrate a population of neurons in the substantia nigra. However, when visualisation was carried out using the routine Nissl method a significant proportion of neurons failed to stain. As the presence of the retrograde tracer did not affect Nissl staining of such cells, such incomplete staining, with consequent underestimation of neuronal populations, is pro...

Early and progressive microstructural brain changes in mice overexpressing human alpha-Synuclein detected by diffusion kurtosis imaging

Czech Academy of Sciences Publication Activity Database

Khairnar, A.; Rudá-Kučerová, J.; Szabó, N.; Dražanová, Eva; Arab, A.; Hutter-Paier, B.; Neddens, J.; Latta, P.; Starčuk jr., Zenon; Rektorová, I.

2017-01-01

Roč. 61, MAR (2017), s. 197-208 ISSN 0889-1591 R&D Projects: GA MŠk(CZ) LO1212; GA MŠk(CZ) LM2015062; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : MRI * diffusion kurtosis imaging * substantia nigra * sriatum * thalamus * TNWT-61 * parkinson's disease * transgenic mice * animal model Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: 1.7 Other natural sciences Impact factor: 5.964, year: 2016

Samuel Thomas Soemmerring (1755-1830): The Naming of Cranial Nerves.

Science.gov (United States)

Pearce, John M S

2017-01-01

Samuel Thomas Soemmerring was a Prussian polymathic doctor with remarkable achievements in anatomy, draftsmanship and inventions. His naming of 12 pairs of cranial nerves in his graduation thesis is of particular importance. He also gave original descriptions of the macula, sensory pathways and of the substantia nigra. His non-medical contributions were diverse and included criticism of the guillotine, invention of a telegraphic system, and discoveries in palaeontology. © 2017 S. Karger AG, Basel.

Serotonin transporter (SERT gene polymorphism in Parkinson’s disease

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Mahmut Özkaya

2004-06-01

Full Text Available Background: Parkinson disease (PD is the second most common neurodegenerative disorder with a prevalence of about 2% in persons older than 65 years of age. Neurodegenerative process in PD is not restricted to the dopaminergic neurons of the substantia nigra but also affects serotoninergic neurons. It has been shown that PD brains with Lewy bodies in the substantia nigra also had Lewy bodies in the raphe nuclei. The re-uptake of 5HT released into the synaptic cleft is mediated by the 5HT transporter (SERT. The SERT gene has been mapped to the chromosome of 17q11.1-q12 and has two main polymorphisms: intron two VNTR polymorphism and promoter region 44 bp insertion/deletion polymorphism. Objective: In this study we investigated whether two polymorphic regions in the serotonin transporter gene are associated with PD. Material and Method: After obtaining informed consent, blood samples were collected from 76 patients and 54 healthy volunteers. Genomic DNA was extracted from peripheral leucocytes using standard methods. The SERT gene genotypes were determined using polymerase chain reaction (PCR method. Results: Based on the intron 2 VNTR polymorphism of SERT gene, the distribution of 12/12, 12/10 and 10/10 genotypes were found as, 56.6 %, 35.5 %, 7.9 % in patients whereas this genotype distribution in control group was 40.7 %, 46.3 % and 13 %, respectively. According to 5-HTTLPR polymorphism, the distribution of L/L, L/S and S/S genotypes were found as 27.6 % 51.3 % and 21.1 % in patients whereas this genotype distribution in control group was 33.4 %, 50.0 % and 16.6 %, respectively. Despite the fact that the genotype distribution of SERT gene polymorphism in patients and control group seemed to be different from each other, this difference was not found to be statistically significant. Conclusion: This finding suggests that polymorphisms within the SERT gene do not play a major role in PD susceptibility in the Turkish population.

White noise improves learning by modulating activity in dopaminergic midbrain regions and right superior temporal sulcus.

Science.gov (United States)

Rausch, Vanessa H; Bauch, Eva M; Bunzeck, Nico

2014-07-01

In neural systems, information processing can be facilitated by adding an optimal level of white noise. Although this phenomenon, the so-called stochastic resonance, has traditionally been linked with perception, recent evidence indicates that white noise may also exert positive effects on cognitive functions, such as learning and memory. The underlying neural mechanisms, however, remain unclear. Here, on the basis of recent theories, we tested the hypothesis that auditory white noise, when presented during the encoding of scene images, enhances subsequent recognition memory performance and modulates activity within the dopaminergic midbrain (i.e., substantia nigra/ventral tegmental area, SN/VTA). Indeed, in a behavioral experiment, we can show in healthy humans that auditory white noise-but not control sounds, such as a sinus tone-slightly improves recognition memory. In an fMRI experiment, white noise selectively enhances stimulus-driven phasic activity in the SN/VTA and auditory cortex. Moreover, it induces stronger connectivity between SN/VTA and right STS, which, in addition, exhibited a positive correlation with subsequent memory improvement by white noise. Our results suggest that the beneficial effects of auditory white noise on learning depend on dopaminergic neuromodulation and enhanced connectivity between midbrain regions and the STS-a key player in attention modulation. Moreover, they indicate that white noise could be particularly useful to facilitate learning in conditions where changes of the mesolimbic system are causally related to memory deficits including healthy and pathological aging.

Mucuna pruriens reduces inducible nitric oxide synthase expression in Parkinsonian mice model.

Science.gov (United States)

Yadav, Satyndra Kumar; Rai, Sachchida Nand; Singh, Surya Pratap

2017-03-01

Parkinson's disease is one of the most common neurodegenerative disease found in aged peoples. Plentiful studies are being conducted to find a suitable and effective cure for this disease giving special impetus on use of herbal plants. The study aimed at investigating the effect of ethanolic extract of Mucuna pruriens (Mp) on level of nitric oxide (NO) in paraquat (PQ) induced Parkinson's disease (PD) mouse model and its subsequent contribution to lipid peroxidation. Twenty four Swiss albino mice were divided into three groups; Control, PQ and PQ+Mp. PQ doses were given intraperitoneally, twice in a week and oral dose of ethanolic extract of Mp seed was given for 9 weeks. Nitrite content and lipid peroxidation was measured in all treated groups along with respective controls. RNA was isolated from the nigrostriatal tissue of control and the treated mice and was reverse transcribed into cDNA. PCR was performed to amplify iNOS mRNA and western blot analysis was performed to check its protein level. We had also perfused the mice in all treated group and performed Tyrosine hydroxylase (TH) and iNOS immunoreactivity in substantia nigra region of mice brain. PQ-treatment increased nitrite content, expression of iNOS and lipid peroxidation compared to respective controls. Mp treatment resulted in a significant attenuation of iNOS expression, nitrite content and lipid peroxidation demonstrating that it reduces nitric oxide in PQ-induced Parkinson's disease. Interestingly; we also observed that mRNA, protein expression and immunoreactivity of iNOS was significantly decreased after Mp treatment and TH immunoreactivity was significantly improved after the treatment of Mp. Our results demonstrated that Mp protects the dopaminergic neurons from the NO injury in substantia nigra. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Boron accumulation and toxicity in hybrid poplar (Populus nigra × euramericana).

Science.gov (United States)

Rees, Rainer; Robinson, Brett H; Menon, Manoj; Lehmann, Eberhard; Günthardt-Goerg, Madeleine S; Schulin, Rainer

2011-12-15

Poplars accumulate high B concentrations and are thus used for the phytomanagement of B contaminated soils. Here, we performed pot experiments in which Populus nigra × euramericana were grown on a substrate with B concentrations ranging from 13 to 280 mg kg(-1) as H(3)BO(3). Salix viminalis, Brassica juncea, and Lupinus albus were grown under some growing conditions for comparison. Poplar growth was unaffected at soil B treatment levels up to 93 mg kg(-1). Growth was progressively reduced at levels of 168 and 280 mg kg(-1). None of the other species survived at these substrate B levels. At leaf B concentrations toxicity. Neutron radiography revealed that chlorotic leaf tissues had B concentrations of 1000-2000 mg kg(-1), while necrotic tissues had >2000 mg kg(-1). Average B concentrations of up to 3500 mg kg(-1) were found in leaves, while spots within leaves had concentrations >7000 mg kg(-1), showing that B accumulation in leaf tissue continued even after the onset of necrosis. The B accumulation ability of P. nigra × euramericana is associated with B hypertolerance in the living tissue and storage of B in dead leaf tissue.

Natural hybridization between Populus nigra L. and P. x canadensis Moench. Hybrid offspring competes for niches along the Rhine river in the Netherlands

NARCIS (Netherlands)

Smulders, M.J.M.; Beringen, R.; Volosyanchuk, R.; Vanden Broeck, A.; Schoot, van der J.; Arens, P.F.P.; Vosman, B.

2008-01-01

Black poplar (Populus nigra L.) is a major species for European riparian forests but its abundance has decreased over the decades due to human influences. For restoration of floodplain woodlands, the remaining black poplar stands may act as source population. A potential problem is that P. nigra and

Lack of neuroprotection in the absence of P2X7 receptors in toxin-induced animal models of Parkinson's disease

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Kittel Ágnes

2011-05-01

Full Text Available Abstract Background Previous studies indicate a role of P2X7 receptors in processes that lead to neuronal death. The main objective of our study was to examine whether genetic deletion or pharmacological blockade of P2X7 receptors influenced dopaminergic cell death in various models of Parkinson's disease (PD. Results mRNA encoding P2X7 and P2X4 receptors was up-regulated after treatment of PC12 cells with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP. P2X7 antagonists protected against MPTP and rotenone induced toxicity in the LDH assay, but failed to protect after rotenone treatment in the MTT assay in PC12 cells and in primary midbrain culture. In vivo MPTP and in vitro rotenone pretreatments increased the mRNA expression of P2X7 receptors in the striatum and substantia nigra of wild-type mice. Basal mRNA expression of P2X4 receptors was higher in P2X7 knockout mice and was further up-regulated by MPTP treatment. Genetic deletion or pharmacological inhibition of P2X7 receptors did not change survival rate or depletion of striatal endogenous dopamine (DA content after in vivo MPTP or in vitro rotenone treatment. However, depletion of norepinephrine was significant after MPTP treatment only in P2X7 knockout mice. The basal ATP content was higher in the substantia nigra of wild-type mice, but the ADP level was lower. Rotenone treatment elicited a similar reduction in ATP content in the substantia nigra of both genotypes, whereas reduction of ATP was more pronounced after rotenone treatment in striatal slices of P2X7 deficient mice. Although the endogenous amino acid content remained unchanged, the level of the endocannabinoid, 2-AG, was elevated by rotenone in the striatum of wild-type mice, an effect that was absent in mice deficient in P2X7 receptors. Conclusions We conclude that P2X7 receptor deficiency or inhibition does not support the survival of dopaminergic neurons in an in vivo or in vitro models of PD.

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

Ozone affects growth and development of Pieris brassicae on the wild host plant Brassica nigra

International Nuclear Information System (INIS)

Khaling, Eliezer; Papazian, Stefano; Poelman, Erik H.; Holopainen, Jarmo K.; Albrectsen, Benedicte R.; Blande, James D.

2015-01-01

When plants are exposed to ozone they exhibit changes in both primary and secondary metabolism, which may affect their interactions with herbivorous insects. Here we investigated the performance and preferences of the specialist herbivore Pieris brassicae on the wild plant Brassica nigra under elevated ozone conditions. The direct and indirect effects of ozone on the plant-herbivore system were studied. In both cases ozone exposure had a negative effect on P. brassicae development. However, in dual-choice tests larvae preferentially consumed plant material previously fumigated with the highest concentration tested, showing a lack of correlation between larval preference and performance on ozone exposed plants. Metabolomic analysis of leaf material subjected to combinations of ozone and herbivore-feeding, and focussing on known defence metabolites, indicated that P. brassicae behaviour and performance were associated with ozone-induced alterations to glucosinolate and phenolic pools. - Highlights: • We examined the effects of ozone on Pieris brassicae performance and preference. • We studied ozone and herbivore induced changes in the metabolome of Brassica nigra. • The performance of P. brassicae did not correlate with preference of ozonated plants. • Ozone and herbivore-feeding stress changes the phytochemical pools of B. nigra. - Ozone indirectly reduces herbivore performance, which is associated with change in phytochemical pools, but does not correlate with host plant preference

Genetic Diversity of Pinus nigra Arn. Populations in Southern Spain and Northern Morocco Revealed By Inter-Simple Sequence Repeat Profiles

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Oussama Ahrazem

2012-05-01

Full Text Available Eight Pinus nigra Arn. populations from Southern Spain and Northern Morocco were examined using inter-simple sequence repeat markers to characterize the genetic variability amongst populations. Pair-wise population genetic distance ranged from 0.031 to 0.283, with a mean of 0.150 between populations. The highest inter-population average distance was between PaCU from Cuenca and YeCA from Cazorla, while the lowest distance was between TaMO from Morocco and MA Sierra Mágina populations. Analysis of molecular variance (AMOVA and Nei’s genetic diversity analyses revealed higher genetic variation within the same population than among different populations. Genetic differentiation (Gst was 0.233. Cuenca showed the highest Nei’s genetic diversity followed by the Moroccan region, Sierra Mágina, and Cazorla region. However, clustering of populations was not in accordance with their geographical locations. Principal component analysis showed the presence of two major groups—Group 1 contained all populations from Cuenca while Group 2 contained populations from Cazorla, Sierra Mágina and Morocco—while Bayesian analysis revealed the presence of three clusters. The low genetic diversity observed in PaCU and YeCA is probably a consequence of inappropriate management since no estimation of genetic variability was performed before the silvicultural treatments. Data indicates that the inter-simple sequence repeat (ISSR method is sufficiently informative and powerful to assess genetic variability among populations of P. nigra.

Reduction of the Nitro Group to Amine by Hydroiodic Acid to Synthesize o-Aminophenol Derivatives as Putative Degradative Markers of Neuromelanin

OpenAIRE

Wakamatsu, Kazumasa; Tanaka, Hitomi; Tabuchi, Keisuke; Ojika, Makoto; Zucca, Fabio; Zecca, Luigi; Ito, Shosuke

2014-01-01

Neuromelanin (NM) is produced in dopaminergic neurons of the substantia nigra (SN) and in noradrenergic neurons of the locus coeruleus (LC). The synthesis of NM in those neurons is a component of brain aging and there is the evidence that this pigment can be involved in the pathogenesis of neurodegenerative diseases such as Parkinson’s disease. NM is believed to derive from the oxidative polymerization of dopamine (DA) or norepinephrine (NE) with the participation of cysteine, dolichols and ...

Isogenic Human iPSC Parkinson’s Model Shows Nitrosative Stress-Induced Dysfunction in MEF2-PGC1α Transcription

OpenAIRE

Ryan, Scott D.; Dolatabadi, Nima; Chan, Shing Fai; Zhang, Xiaofei; Akhtar, Mohd Waseem; Parker, James; Soldner, Frank; Sunico, Carmen R.; Nagar, Saumya; Talantova, Maria; Lee, Brian; Lopez, Kevin; Nutter, Anthony; Shan, Bing; Molokanova, Elena

2013-01-01

Parkinson’s disease (PD) is characterized by loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). An association has been reported between PD and exposure to mitochondrial toxins, including environmental pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived stem cell model of PD allowing comparison of A53T α-synuclein (α-syn) mutant cells and isogenic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations in A...

Bipolar disorder, a precursor of Parkinson's disease?

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Tânia M.S. Novaretti

Full Text Available ABSTRACT Parkinson's disease is a neurodegenerative disorder predominantly resulting from dopamine depletion in the substantia nigra pars compacta. Some psychiatric disorders may have dopaminergic dysfunction as their substrate. We describe a well-documented case of Parkinson's disease associated with Bipolar Disorder. Although there is some knowledge about the association between these diseases, little is known about its pathophysiology and correlation. We believe that among various hypotheses, many neurotransmitters are linked to this pathophysiology.

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

Ultrasonic surface measurements at the Porta Nigra, Trier, and the Neptungrotte, Park Sanssouci Potsdam

Science.gov (United States)

Meier, Thomas; Auras, Michael; Fehr, Moritz; Köhn, Daniel

2015-04-01

Ultrasonic measurements along profiles at the surface of an object are well suited to characterize non-destructively weathering of natural stone near the surface. Ultrasonic waveforms of surface measurements in the frequency range between 10 kHz and 300 kHz are often dominated by the Rayleigh wave - a surface wave that is mainly sensitive to the velocity and attenuation of S-waves in the upper 0.3 cm to 3 cm. The frequency dependence of the Rayleigh wave velocity may be used to analyze variations of the material properties with depth. Applications of ultrasonic surface measurements are shown for two buildings: the Roman Porta Nigra in Trier from the 3rd century AD and the Neptungrotte at Park Sanssouci in Potsdam designed by von Knobelsdorff in the 18th century. Both buildings belong to the world cultural heritage and restorations are planned for the near future. It is interesting to compare measurements at these two buildings because they show the applicability of ultrasonic surface measurements to different natural stones. The Porta Nigra is made of local sandstones whereas the facades of the Neptungrotte are made of Carrara and Kauffunger marble. 71 and 46 surface measurements have been carried out, respectively. At both buildings, Rayleigh-wave group velocities show huge variations. At the Porta Nigra they vary between ca. 0.4 km/s and 1.8 km/s and at the Neptungrotte between ca. 0.7 km/s and 3.0 km/s pointing to alterations in the Rayleigh- and S-wave velocities of more than 50 % due to weathering. Note that velocities of elastic waves may increase e.g. because of the formation of black crusts like at the Porta Nigra or they may be strongly reduced due to weathering. The accuracy of the ultrasonic surface measurements, its reproducibility, and the influence of varying water saturation are discussed. Options for the analysis of ultrasonic waveforms are presented ranging from dispersion analysis to full waveform inversions for one-dimensional and two

Species delimitation in asexual insects of economic importance: The case of black scale (Parasaissetia nigra, a cosmopolitan parthenogenetic pest scale insect.

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Yen-Po Lin

Full Text Available Asexual lineages provide a challenge to species delimitation because species concepts either have little biological meaning for them or are arbitrary, since every individual is monophyletic and reproductively isolated from all other individuals. However, recognition and naming of asexual species is important to conservation and economic applications. Some scale insects are widespread and polyphagous pests of plants, and several species have been found to comprise cryptic species complexes. Parasaissetia nigra (Nietner, 1861 (Hemiptera: Coccidae is a parthenogenetic, cosmopolitan and polyphagous pest that feeds on plant species from more than 80 families. Here, we implement multiple approaches to assess the species status of P. nigra, including coalescence-based analyses of mitochondrial and nuclear genes, and ecological niche modelling. Our results indicate that the sampled specimens of P. nigra should be considered to comprise at least two ecotypes (or "species" that are ecologically differentiated, particularly in relation to temperature and moisture. The presence of more than one ecotype under the current concept of P. nigra has implications for biosecurity because the geographic extent of each type is not fully known: some countries may currently have only one of the biotypes. Introduction of additional lineages could expand the geographic extent of damage by the pest in some countries.

Morus nigra plant leaves as biomonitor for elemental air pollution monitoring

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Daud, M.; Khalid, N.; Waheed, S.; Wasim, M.; Arif, M.; Zaidi, J.H. [Pakistan Institute of Nuclear Science and Technology, Islamabad (Pakistan). Chemistry Div.

2011-07-01

The present paper deals with the determination of 36 elements in 120 leaf samples of Morus nigra plant to assess their potential as biomonitor for elemental air pollution monitoring. The elemental quantification was made by employing Instrumental Neutron Activation Analysis (INAA) and Atomic Absorption Spectrometric (AAS) techniques. The leaf samples were collected in spring, summer and winter seasons from various sites in Islamabad with different types of anthropogenic activities as well as from a reference site with minimum of such activities. Twenty four soil samples from the respective sites were also analyzed. The reliability of the adopted procedures was established by analyzing the certified reference materials, i.e., citrus leaves-1572 and soil-7, from NIST and IAEA, respectively, under identical experimental conditions and comparing the results obtained with the certified values which are in quite good agreement with each other. The enrichment values and Pollution Load Index (PLI) of the determined elements were computed and discussed accordingly. The elemental translocation from soil to roots, stem and leaves has also been studied by analyzing these parts of the same plant. The results indicated that the leaves of Morus nigra plant have promising potential to monitor the extent of air pollution in the vicinity of industrial as well as in high traffic areas. (orig.)

Da-Bu-Yin-Wan and Qian-Zheng-San to Neuroprotect the Mouse Model of Parkinson’s Disease

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Xiao-Gang Gong

2014-01-01

Full Text Available Da-Bu-Yin-Wan (DBYW and Qian-Zheng-San (QZS, two classic traditional Chinese medicinal formulas, were clinically employed to treat Parkinson’s disease (PD. Our previous studies demonstrated neuroprotective effects of them on mitochondrial function in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. The purpose of this research was to investigate their possible mechanisms in the light of mitochondrial ATP-sensitive potassium (mitoKATP channels. The neuroprotective effect of DBYW and QZS on dopamine (DA neurons in substantia nigra (SN in the MPTP-induced PD mice was investigated by behavioral test (pole test and immunohistochemistry. Adenosine triphosphate (ATP level in the midbrain tissue was detected by firefly luciferase method. MitoKATP channel subunits SUR1 and Kir6.2 mRNA and protein expressions were tested by real-time PCR (RT-PCR and Western blot. It was observed that DBYW and/or QZS served to ameliorate MPTP-induced behavioral impairment and prevent the loss of substantia nigra dopamine neurons, as well as increase ATP level in the midbrain tissue and downregulate SUR1 expression at mRNA and protein levels with no marked influence on Kir6.2. We concluded that DBYW and QZS exhibit neuroprotective effects probably through the regulation of ATP level and mitoKATP channel subunit expressions.

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

Science.gov (United States)

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

The role of brain magnetic resonance imaging in the diagnosis of pantothenate kinase deficiency (previously Hallervorden-Spatz disease): case report; Znaczenie badania tomografii rezonansu magnetycznego mozgowia w diagnostyce deficytu kinazy pantotenowej (dawniej choroby Hallervordena-Spatza) - opis przypadku

Energy Technology Data Exchange (ETDEWEB)

Gizewska, M; Bieleninik, A; Adamczyk, T; Walczak, M [II Klinika Chorob Dzieci Pomorskiej Akademii Medycznej, Szczecin (Poland); Cyrylowski, L [Zaklad Diagnostyki Obrazowej i Radiologii Interwencyjnej Pomorskiej Akademii Medycznej, Szczecin (Poland); Abramczyk, G [Oddzial Noworodkow, Patologii i Intensywnej Terapii, Samodzielnego Publicznego Specjalistycznego ZOZ ' ' Zdroje ' ' , Szczecin (Poland); Nowacki, P [Klinika Neurologii Pomorskiej Akademii Medycznej, Szczecin (Poland)

2005-07-01

Panthotenate kinase deficiency is a rare metabolic disorder from the group of neuroaxonal dystrophy. It is characterized by symptoms of extrapiramidal system impairment, general dystonia, progressive gait disturbances, limbs rigidity, dyskinesias, choreoatetotic movements, dysarthria and progressive dementia. On the brain MRI, T2 - weighted images demonstrate typical, symmetrical '' eye of the tiger '' sign with hyperintensive signals from the central parts of the pallidum, surrounded by low signals in the pallidum and accompanied by hypointensity in substantia nigra resulting from iron deposition. We present a case of 13.5 year old boy with gait disturbances, increase muscles tone, dysartria, aggressive behavior and learning difficulties progressing from the early childhood. In the differential diagnosis a number of inborn errors of metabolism was excluded. Finding on the brain MRI in T2- weighted images typical picture of '' eye of the tiger '' led to a diagnosis of panthotenate kinase deficiency. In subsequent years of observation, despite attempts of baclofen and calcium panthotenate treatment, progression of pyramidal-extrapyramidal syndrome is observed. In children with symptoms of progressive extrapyramidal tract impairment, a sign of '' eye of the tiger '' with hyperintensive signals from the central parts of the pallidum, surrounded by low signals in the remaining part of the pallidum and accompanied by similar lesions in substantia nigra is typical for panthotenate kinase deficiency - a rare neurodegenerative disorder of central nervous system. (author)

The Effects of Melatonin with Memantin on MPTP-Induced Parkinson Model in Male Mice

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Reza Talebi

2015-09-01

Full Text Available Abstract Background: Oxidative stress and severe neuro-excitation have significant effects on pathogenesis of Parkinson’s disease and agents with antioxidant property can potentially prevent these effects. Herein we examined potential protective effects of melatonin as an antioxidant agent and memantine as an uncompetitive receptor of NMDA, on a model of Parkinson’s disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP. Materials and Methods: Male mice were divided into 8 groups with 7 mice in each group: saline, ethanol, melatonin, memantin, MPTP, melatonin+MPTP, memantin+ MPTP, melatonin+ memantin+ MPTP. All of agents were injected intraperitoneally once a day for 14 days before beam traversal test. Dopaminergic neurons of the Substantia Nigra Pars compacta (SNPC were determined by immunohistochemical and were counted. Results: Melatonin improved notably movement dysfunction resulted of MPTP such as the number of errors, paces and the time of movement during behavioral test and also the counting of neurons of Substantia Nigra Pars Compacta. Memantin had a synergic effect on the most of improvements. However, the level of improvement and retrieval of signs was not as in saline and ethanol groups. Conclusion: Melatonin especially together with memantine is able to prevent some of the MPTP-induced dysfunctions. However, the protective effects were not enogh, probably because of the amount of dose and the time of injection.

A novel dual GLP-1 and GIP incretin receptor agonist is neuroprotective in a mouse model of Parkinson's disease by reducing chronic inflammation in the brain.

Science.gov (United States)

Cao, Lijun; Li, Dongfang; Feng, Peng; Li, Lin; Xue, Guo-Fang; Li, Guanglai; Hölscher, Christian

2016-04-13

The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are growth factors. GLP-1 mimetics are on the market as treatments for type 2 diabetes. Both GLP-1 and GIP mimetics have shown neuroprotective properties in previous studies. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed to treat diabetes. Here, we report the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once daily (20 mg/kg intraperitoneally) for 7 days and the dual agonist was coinjected once daily (50 nmol/kg intraperitoneally). We found that the drug reduced most of the MPTP-induced motor impairments in the rotarod, open-field locomotion, and muscle strength test. The number of tyrosine hydroxylase-positive neurons in the substantia nigra and striatum was reduced by MPTP and increased by DA-JC1. Synapse numbers (synaptophysin expression) were reduced in the substantia nigra and the striatum by MPTP and DA-JC1 reversed this effect. The activation of a chronic inflammation response by MPTP was considerably reduced by the dual agonist (DA) (astroglia and microglia activation). Therefore, dual agonists show promise as a novel treatment of PD.

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.

Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.

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Tomáš Sieger

Full Text Available The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control.

Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.

Science.gov (United States)

Sieger, Tomáš; Bonnet, Cecilia; Serranová, Tereza; Wild, Jiří; Novák, Daniel; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen; Gaymard, Bertrand; Jech, Robert

2013-01-01

The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control.

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

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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.

Copper and Copper Proteins in Parkinson's Disease

Science.gov (United States)

Rivera-Mancia, Susana; Diaz-Ruiz, Araceli; Tristan-Lopez, Luis; Rios, Camilo

2014-01-01

Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology. PMID:24672633

Copper and Copper Proteins in Parkinson’s Disease

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Sergio Montes

2014-01-01

Full Text Available Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson’s disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson’s disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson’s disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson’s disease and that a mutation in ATP7B could be associated with Parkinson’s disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology.

Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques.

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Katsuo Kimura

Full Text Available In neurodegenerative disorders, such as Parkinson's disease (PD, alpha-synuclein (α-syn accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB. This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.

Autoradiography of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): Uptake in the monoaminergic pathways and in melanin containing tissues

Energy Technology Data Exchange (ETDEWEB)

Lyden, A; Lindquist, N G; Bondesson, U; Larsson, B S; Olsson, L -I

1985-01-01

A recently discovered neurotoxic compound, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, has been found to cause a parkinsonian-like syndrome in man and monkey, but not in laboratory animals such as rat, mouse and guinea pig. MPTP seems to selectively destroy the melanin containing dopaminergic cells in pars compacta of substantia nigra. Lower mammalian species do not have melanin in these cells, which indicates that the presence of neuromelanin may be of importance for the development of MPTP-induced lesions. By means of whole-body autoradiography of TH-MPTP in mice, accumulation and retention was observed in the dopaminergic pathways, in locus ceruleus and in structures in the medulla oblongata and spinal cord. A high uptake was also seen in melanin-containing tissues such as in the eyes of pigmented mice. MPTP has earlier been found to have high affinity in vitro for dopamine melanin, which is similar to the pigment in substantia nigra. The typical features of the MPTP-induced neurotoxicity with destruction of pigmented nerve cells and development of parkinsonism may be due to accumulation adn retention of MPTP and its metabolites in these cells. In species with pigmented nerve cells, such as man and monkey, the accumulation may be much more pronounced because of the melanin affinity of MPTP and its metabolites. (author).

The role of brain magnetic resonance imaging in the diagnosis of pantothenate kinase deficiency (previously Hallervorden-Spatz disease): case report

International Nuclear Information System (INIS)

Gizewska, M.; Bieleninik, A.; Adamczyk, T.; Walczak, M.; Cyrylowski, L.; Abramczyk, G.; Nowacki, P.

2005-01-01

Panthotenate kinase deficiency is a rare metabolic disorder from the group of neuroaxonal dystrophy. It is characterized by symptoms of extrapiramidal system impairment, general dystonia, progressive gait disturbances, limbs rigidity, dyskinesias, choreoatetotic movements, dysarthria and progressive dementia. On the brain MRI, T2 - weighted images demonstrate typical, symmetrical '' eye of the tiger '' sign with hyperintensive signals from the central parts of the pallidum, surrounded by low signals in the pallidum and accompanied by hypointensity in substantia nigra resulting from iron deposition. We present a case of 13.5 year old boy with gait disturbances, increase muscles tone, dysartria, aggressive behavior and learning difficulties progressing from the early childhood. In the differential diagnosis a number of inborn errors of metabolism was excluded. Finding on the brain MRI in T2- weighted images typical picture of '' eye of the tiger '' led to a diagnosis of panthotenate kinase deficiency. In subsequent years of observation, despite attempts of baclofen and calcium panthotenate treatment, progression of pyramidal-extrapyramidal syndrome is observed. In children with symptoms of progressive extrapyramidal tract impairment, a sign of '' eye of the tiger '' with hyperintensive signals from the central parts of the pallidum, surrounded by low signals in the remaining part of the pallidum and accompanied by similar lesions in substantia nigra is typical for panthotenate kinase deficiency - a rare neurodegenerative disorder of central nervous system. (author)

Germinação de sementes de dalbergia nigra (Vell. Allemao ex Benth. (Fabaceae-Papilionoideae no armazenamento Germination of Dalbergia nigra (Vell. Allemao ex Benth. (Fabaceae-Papilionoideae during storage

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Francismar Francisco Alves Aguiar

2010-12-01

Full Text Available Dalbergia nigra (Vell. Allemao ex Benth. (jacarandá-da-bahia, espécie de alto valor econômico pela qualidade da madeira e potencial ornamental em razão da copa bem formada e à delicadeza da folhagem, está na lista de espécies ameaçadas de extinção. Em função disso, conduziu-se este trabalho, visando à avaliação da qualidade de suas sementes, submetidas a períodos crescentes de armazenamento. Os frutos foram coletados em outubro de 2003, e as sementes armazenadas em geladeira a 6º C ± 2, em sacos de plástico transparente fechados. Mensalmente, durante 690 dias, foram retiradas 200 sementes, sendo que 100 foram utilizadas nos ensaios de germinação (quatro repetições de 25 sementes e 100 para a determinação do teor de água. Os ensaios germinativos foram conduzidos em estufa tipo B.O.D., a 25º C e com fotoperíodo de 12 horas. As variáveis analisadas foram a porcentagem de germinação, índice de velocidade de germinação e massa seca das plântulas originadas. Os resultados indicaram que, até 360 dias de armazenamento, as sementes apresentaram porcentagem de germinação próxima de 50%, com redução de cerca da metade do índice de velocidade de germinação, porém, com maior comprometimento do acúmulo da massa seca das plântulas. A porcentagem de germinação inicial e final foram de 87% e 36%, respectivamente. As sementes de D. nigra têm comportamento ortodoxo e podem ser armazenadas por um período de até dois anos em sacos de plástico a baixa temperatura, com redução em cerca de 50% de sua capacidadeDalbergia nigra (Vell. Allemao ex Benth. (Brazilian rosewood is a highly economically valuable species because of its wood quality and ornamental potential, mainly due to its well formed canopy and the delicacy of its foliage. Unfortunately, these features contributed to list it as an endangered Brazilian species (IBAMA Regulation number 06/92. This work had as its objective to study the quality of Dalbergia

Tinea versicolor, tinea nigra, white piedra, and black piedra.

Science.gov (United States)

Bonifaz, Alexandro; Gómez-Daza, Fernando; Paredes, Vanessa; Ponce, Rosa María

2010-03-04

Superficial mycoses are fungal infections limited to the stratum corneum and its adnexal structures. The most frequent types are dermatophytoses or tineas. Tinea versicolor involves the skin in the form of hypochromic or hyperchromic plaques, and tinea nigra affects the skin of the palms with dark plaques. White piedra and black piedra are parasitic infections of scalp hairs in the form of concretions caused by fungal growth. Diagnosis of these mycoses is made from mycologic studies, direct examination, stains, and isolation, and identification of the fungi. Treatment includes systemic antifungals, topical antifungals, and keratolytics. Copyright 2010 Elsevier Inc. All rights reserved.

Biphasic and region-specific MAO-B response to aging in normal human brain.

Science.gov (United States)

Saura, J; Andrés, N; Andrade, C; Ojuel, J; Eriksson, K; Mahy, N

1997-01-01

Variations of monoamine oxidases (MAO) A and B were studied during aging in 27 human subjects (age range 17-93 years) in 18 brain structures of temporal cortex, frontal gyrus, hippocampal formation, striatum, cerebellum, and brainstem. [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. Postmortem delay or time of tissue storage did not affect MAO-A or MAO-B levels. There was, moreover, no evidence of sexual dimorphism. A marked age-related increase in MAO-B was observed in most structures. This increase started at the age of 50-60 years. Before this age, MAO-B levels were constant in all structures studied. MAO-B-rich senile plaques were observed in some cortical areas but they did not significantly influence the age-related MAO-B increase. Surprisingly, no age-related MAO-B changes were observed in the substantia nigra. In contrast to MAO-B, no clear age-related changes in MAO-A were observed, indicating an independent regulation of the two isoenzymes, also suggested by the cross-correlation analysis of these data.

Tinea corporis, tinea cruris, tinea nigra, and piedra.

Science.gov (United States)

Gupta, Aditya K; Chaudhry, Maria; Elewski, Boni

2003-07-01

Tinea infections are among the most common dermatologic conditions throughout the world. To avoid a misdiagnosis, identification of dermatophyte infections requires both a fungal culture on Sabouraud's agar media, and a light microscopic mycologic examination from skin scrapings. Topical antifungals may be sufficient for treatment of tinea corporis and cruris and tinea nigra, and the shaving of hair infected by piedra may also be beneficial. Systemic therapy, however, may be required when the infected areas are large, macerated with a secondary infection, or in immunocompromised individuals. Preventative measures of tinea infections include practicing good personal hygiene; keeping the skin dry and cool at all times; and avoiding sharing towels, clothing, or hair accessories with infected individuals.

Imaging of dopaminergic system in movement disorders

International Nuclear Information System (INIS)

Kim, Yu Kyeong; Kim, Sang Eun

2007-01-01

Parkinson's disease is a common neurodegenerative disorder that is mainly caused by dopaminergic neuron loss in the substantia nigra. Several radiopharmaceutics have been developed to evaluated the integrity of dopaminergic neuronal system. In vivo PET and SPECT imaging of presynaptic dopamine imaging are already applied to Parkinson's disease and other parkinsonism, and can demonstrate the dopaminergic dysfunction. This review summarized the use of the presynaptic dopaminergic imaging in PD as biomarkers in evaluation of disease progression as well as in diagnosis of PD

Iron and Lactoferrin Levels Remain Unchanged in Parkin Deficient Mouse Brains: Implications for Parkinson’s Disease Etiology

OpenAIRE

Baker, Hanan

2015-01-01

Parkinson’s disease is a devastating neurodegenerative disease in which loss of dopaminergic neurons in the substantia nigra pars compacta leads to a variety of motor and non-motor deficits. Mutations in the Park2 or parkin gene have been implicated in familial forms of Parkinson’s disease. Parkin is an E3 ubiquitin ligase that plays a role in mitophagy, the degradation of damaged mitochondria. Defects in parkin are thought to impair mitophagy, leading to mitochondrial dysfunction and an incr...

Overexpression of miR-185 inhibits autophagy and apoptosis of dopaminergic neurons by regulating the AMPK/mTOR signaling pathway in Parkinson's disease

OpenAIRE

Wen, Zhi; Zhang, Jie; Tang, Peng; Tu, Ning; Wang, Ke; Wu, Guangyao

2017-01-01

Parkinson's disease (PD) is an age-associated neurodegenerative disorder characterized by the death of dopaminergic neurons in the substantia nigra pars compacta. Activation of 5′-adenosine monophosphate-activated protein kinase (AMPK) has been suggested to be associated with PD pathogenesis. The aim of the present study was to investigate the effects of the aberrant expression of microRNA-185 (miR-185) in PD. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced in vitro model of PD ...

Pantothenate kinase 2 mutation with classic pantothenate-kinase-associated neurodegeneration without 'eye-of-the-tiger' sign on MRI in a pair of siblings

International Nuclear Information System (INIS)

Zolkipli, Zarazuela; Surtees, Robert; Dahmoush, Hisham; Saunders, Dawn E.; Kling Chong, W.K.

2006-01-01

It has been postulated that all patients with pantothenate kinase 2 (PANK2) mutations causing pantothenate-kinase-associated neurodegeneration (PKAN) are associated with the 'eye-of-the-tiger' sign on MRI. We report a pair of siblings who presented with dystonia and who have been found to be homozygous for 104C>A, S35X mutation, confirming the diagnosis of PKAN. They do not have the typical iron deposition in the globi pallida or substantia nigra on MR imaging. (orig.)

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)

MRI of Wolfram syndrome (DIDMOAD)

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Galluzzi, P.; Filosomi, G.; Vallone, I.M.; Venturi, C. [Dept. of Neuroradiology, Policlinico ' ' Le Scotte' ' , Siena (Italy); Bardelli, A.M. [Dept. of Ophthalmological Sciences, Unit of Paediatric Ophthalmology, University of Siena (Italy)

1999-10-01

Wolfram syndrome (DIDMOAD) is a rare diffuse neurodegenerative disorder characterised by diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and a wide variety of abnormalities of the central nervous system, urinary tract and endocrine glands. It may be familial or sporadic. Reported features on MRI of the brain are absence of the physiological high signal of the posterior lobe of the pituitary, shrinkage of optic nerves, chiasm and tracts, atrophy of the hypothalamic region, brain stem, cerebellum, and cerebral cortex. We report a 12-year-old girl with a 5-year history without brain stem, cerebellar or cerebral atrophy. MRI showed an unusual feature: a focus of high signal on PD- and T2-weighted images in the right substantia nigra. This is consistent with previously reported neuropathological post-mortem studies, but has never been reported in vivo. (orig.)

MRI of Wolfram syndrome (DIDMOAD)

International Nuclear Information System (INIS)

Galluzzi, P.; Filosomi, G.; Vallone, I.M.; Venturi, C.; Bardelli, A.M.

1999-01-01

Wolfram syndrome (DIDMOAD) is a rare diffuse neurodegenerative disorder characterised by diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and a wide variety of abnormalities of the central nervous system, urinary tract and endocrine glands. It may be familial or sporadic. Reported features on MRI of the brain are absence of the physiological high signal of the posterior lobe of the pituitary, shrinkage of optic nerves, chiasm and tracts, atrophy of the hypothalamic region, brain stem, cerebellum, and cerebral cortex. We report a 12-year-old girl with a 5-year history without brain stem, cerebellar or cerebral atrophy. MRI showed an unusual feature: a focus of high signal on PD- and T2-weighted images in the right substantia nigra. This is consistent with previously reported neuropathological post-mortem studies, but has never been reported in vivo. (orig.)

Immunomodulators as Therapeutic Agents in Mitigating the Progression of Parkinson’s Disease

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Bethany Grimmig

2016-09-01

Full Text Available Parkinson’s disease (PD is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of PD, and are implicated in the cell death in this region. Neuroinflammation is evidently involved in PD pathology and mitigating the inflammatory cascade has been a therapeutic strategy. Age is the number one risk factor for PD and thus needs to be considered in the context of disease pathology. Here, we discuss the role of neuroinflammation within the context of aging as it applies to the development of PD, and the potential for two representative compounds, fractalkine and astaxanthin, to attenuate the pathophysiology that modulates neurodegeneration that occurs in Parkinson’s disease.

Testing applicability of black poplar (Populus nigra L.) bark to heavy metal air pollution monitoring in urban and industrial regions

International Nuclear Information System (INIS)

Berlizov, A.N.; Blum, O.B.; Filby, R.H.; Malyuk, I.A.; Tryshyn, V.V.

2007-01-01

A comparative study of the capabilities of black poplar-tree (Populus nigra L.) bark as a biomonitor of atmospheric heavy-metal pollution is reported. Performance indicators (concentrations and enrichment factors) of heavy metal bioaccumulation of bark were compared to the corresponding indicators of epiphytic lichens Xanthoria parietina (L.) Th. Fr. and Physcia adscendens (Fr.) H. Oliver, collected simultaneously with bark samples within the Kiev urban-industrial conurbation. The concentrations of 40 minor and trace elements in the samples were measured by a combination of epithermal and instrumental neutron activation analysis (NAA) using a 10 MW nuclear research reactor WWR-M as the neutron source. Statistical analysis of the data was carried out using non-parametric tests. It was shown that for the majority of the elements determined a good correlation exists between their concentrations in bark and in the lichen species. The accumulation capability of the bark was found to be as effective as, and in some cases better, for both types of lichens. Based on the background levels and variations of the elemental concentration in black poplar-tree bark, threshold values for the enrichment factors were established. For a number of elements (As, Au, Ce, Co, Cr, Cu, La, Mn, Mo, Ni, Sb, Sm, Ti, Th, U, V, W) an interspecies calibration was performed. An optimized pre-irradiation treatment of the bark sample was employed which efficiently separated the most informative external layer from the deeper layers of the bark and thus minimized variations of the element concentrations. Results of this study support black poplar-tree bark as an alternative to epiphytic lichens for heavy metal air pollution monitoring in urban and industrial regions, where severe environmental conditions may result in scarcity or even lack of the indicator species

Systemic injection of kainic acid: Gliosis in olfactory and limbic brain regions quantified with [3H]PK 11195 binding autoradiography

International Nuclear Information System (INIS)

Altar, C.A.; Baudry, M.

1990-01-01

Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of [3H]PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in [3H]PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in [3H]PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of [3H]PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in [3H]PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of [3H]PK 11195 is a valuable tool to quantify the extent of neuronal degeneration

Age and Parkinson's disease-related neuronal death in the substantia nigra pars compacta

DEFF Research Database (Denmark)

Eriksen, Nina; Stark, Anette Kirstine; Pakkenberg, Bente

2009-01-01

During aging, decline in memory and cognitive abilities as well as motor weakening is of great concern. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. A common neurodegenerative disorder of this s......During aging, decline in memory and cognitive abilities as well as motor weakening is of great concern. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. A common neurodegenerative disorder...

Autoradiographic localization of GABA-regulated chloride ionophore binding site using t-[3H]butylbicycloorthobenzoate (TBOB)

International Nuclear Information System (INIS)

O'Connor, L.H.; McEwen, B.S.

1986-01-01

t-Butylbicycloorthobenzoate (TBOB) has been shown to bind with high affinity to sites on or near the chloride ionophore in rat brain membrane preparations. The present study used in vitro quantitative autoradiography to localize the regional distribution of [ 3 H]TBOB binding sites in rat forebrain. Receptors were labelled with 10 nM [ 3 H]TBOB. Nonspecific binding was determined by adding 10 μM picrotoxin to the incubation. Autoradiograms were generated using LKB Ultrofilm and then quantitated using computer-assisted spot-densitometry. The highest specific binding was found in frontal cortex layer 4, islands of Calleja, and ventral palladium. High binding was also found in many regions including anterior hypothalamic n., ventromedial hypothalamic n., dentate gyrus, stratum oriens and stratum lacunosum moleculare of hippocampus, and substantia nigra. Nonspecific binding represented 5 to 15% of total binding and was uniformly low throughout all brain regions. Thus, this selective probe for GABA-regulated chloride ionophore binding sites should provide a useful tool for characterizing this system and its relationship to convulsant and depressant drug action

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice.

Science.gov (United States)

Paul, Rajib; Borah, Anupom

2017-12-20

There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.

Green synthesis of silver nanoparticles from seed extract of Brassica nigra and its antibacterial activity

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RAKSHA PANDIT

2015-05-01

Full Text Available Pandit R. 2015. Green synthesis of silver nanoparticles from seed extract of Brassica nigra and its antibacterial activity. Nusantara Bioscience 7: 15-19. We report the green synthesis of silver nanoparticles using seed extract of Brassica nigra. UV-visible spectroscopic analysis showed the absorbance peak at 432 nm which indicated the synthesis of silver nanoparticles. Nanoparticles Tracking and Analysis (NTA was used to determine the size of synthesized silver nanoparticles. Zeta potential analysis was carried out to study the stability of nanoparticles while FTIR analysis confirmed the presence of proteins as capping agents that provided stability to nanoparticles in colloid. Antibacterial activity of silver nanoparticles was evaluated against Propionibacterium acnes, Pseudomonas aeruginosa and Klebsiella pneumoniae. The activity of Vancomycin was significantly increased in combination with silver nanoparticles showing synergistic activity against all bacteria while the maximum activity was noted against P. acnes.

Habitat characteristics at den sites of the Point Arena mountain beaver (Aplodontia rufa nigra)

Science.gov (United States)

William J. Zielinski; John E. Hunter; Robin Hamlin; Keith M. Slauson; M. J. Mazurek

2010-01-01

The Point Arena mountain beaver (Aplodontia rufa nigra) is a federally listed endangered species, but has been the subject of few studies. Mountain beavers use burrows that include a single subterranean den. Foremost among the information needs for this subspecies is a description of the above-ground habitat features associated with dens. Using...

Patterns of Cell Activity in the Subthalamic Region Associated with the Neuroprotective Action of Near-Infrared Light Treatment in MPTP-Treated Mice

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Victoria E. Shaw

2012-01-01

Full Text Available We have shown previously that near-infrared light (NIr treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subthalamic region, namely, the subthalamic nucleus (STN and zona incerta (ZI; both cell groups have abnormally overactive cells in parkinsonian cases. BALB/c mice were treated with MPTP (100–250 mg/kg or saline either over 30 hours followed by either a two-hour or six-day survival period (acute model or over five weeks followed by a three-week survival period (chronic model. NIr and MPTP were applied simultaneously. Brains were processed for Fos immunochemistry, and cell number was estimated using stereology. Our major finding was that NIr treatment reduced (30–45% the increase in Fos+ cell number evident in the STN and ZI after MPTP insult. This reduction was concurrent with the neuroprotection of dopaminergic SNc cells shown previously and was evident in both MPTP models (except for the 2 hours survival period which showed no changes in cell number. In summary, our results indicated that NIr had long lasting effects on the activity of cells located deep in the brain and had repaired partially the abnormal activity generated by the parkinsonian toxin.

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

CyPPA, a Positive SK3/SK2 Modulator, Reduces Activity of Dopaminergic Neurons, Inhibits Dopamine Release, and Counteracts Hyperdopaminergic Behaviors Induced by Methylphenidate

DEFF Research Database (Denmark)

Herrik, Kjartan F; Redrobe, John P; Holst, Dorte

2012-01-01

Dopamine (DA) containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson's disease. Pharmacological......]-amine (CyPPA), a subtype-selective positive modulator of SK channels (SK3¿>¿SK2¿>¿>¿>¿SK1, IK), decreased spontaneous firing rate, increased the duration of the apamin-sensitive afterhyperpolarization, and caused an activity-dependent inhibition of current-evoked action potentials in DA neurons from both...

Functional and ultrastructural neuroanatomy of interactive intratectal/tectonigral mesencephalic opioid inhibitory links and nigrotectal GABAergic pathways: involvement of GABAA and mu1-opioid receptors in the modulation of panic-like reactions elicited by electrical stimulation of the dorsal midbrain.

Science.gov (United States)

Ribeiro, S J; Ciscato, J G; de Oliveira, R; de Oliveira, R C; D'Angelo-Dias, R; Carvalho, A D; Felippotti, T T; Rebouças, E C C; Castellan-Baldan, L; Hoffmann, A; Corrêa, S A L; Moreira, J E; Coimbra, N C

2005-12-01

In the present study, the functional neuroanatomy of nigrotectal-tectonigral pathways as well as the effects of central administration of opioid antagonists on aversive stimuli-induced responses elicited by electrical stimulation of the midbrain tectum were determined. Central microinjections of naloxonazine, a selective mu(1)-opiod receptor antagonist, in the mesencephalic tectum (MT) caused a significant increase in the escape thresholds elicited by local electrical stimulation. Furthermore, either naltrexone or naloxonazine microinjected in the substantia nigra, pars reticulata (SNpr), caused a significant increase in the defensive thresholds elicited by electrical stimulation of the continuum comprised by dorsolateral aspects of the periaqueductal gray matter (dlPAG) and deep layers of the superior colliculus (dlSC), as compared with controls. These findings suggest an opioid modulation of GABAergic inhibitory inputs controlling the defensive behavior elicited by MT stimulation, in cranial aspects. In fact, iontophoretic microinjections of the neurotracer biodextran into the SNpr, a mesencephalic structure rich in GABA-containing neurons, show outputs to neural substrate of the dlSC/dlPAG involved with the generation and organization of fear- and panic-like reactions. Neurochemical lesion of the nigrotectal pathways increased the sensitivity of the MT to electrical (at alertness, freezing and escape thresholds) and chemical (blockade of GABA(A) receptors) stimulation, suggesting a tonic modulatory effect of the nigrotectal GABAergic outputs on the neural networks of the MT involved with the organization of the defensive behavior and panic-like reactions. Labeled neurons of the midbrain tectum send inputs with varicosities to ipsi and contralateral dlSC/dlPAG and ipsilateral substantia nigra, pars reticulata and compacta, in which the anterograde and retrograde tracing from a single injection indicates that the substantia nigra has reciprocal connections with

Comparative study on bioremediation of heavy metals by solitary ascidian, Phallusia nigra, between Thoothukudi and Vizhinjam ports of India.

Science.gov (United States)

Abdul Jaffar Ali, H; Tamilselvi, M; Akram, A Soban; Kaleem Arshan, M L; Sivakumar, V

2015-11-01

Ascidians belonging to the sub-phylum Uro-chordata are used as potential model organisms in various parts of the world for biosorption of metals. The sedentary nature, filter feeding habits, presence of vanadocytes and the absence of kidneys cause them to accumulate metals. The present study was aimed to compare biosorption of metals such as cadmium, copper, lead, mercury and vanadium in test and mantle body of solitary ascidian Phallusia nigra between two ecologically significant stations such as Thoothukudi (Station 1) and Vizhinjam (Station 2) ports of India. Monthly samplings of water and P. nigra were done for a period of one year from September 2010 to August 2011 and subjected to analysis of metal accumulation. The average metal concentrations except mercury in the Thoothukudi water were found to be higher of comparable magnitudes than the Vizhinjam water. One-way ANOVA showed significant differences between the stations. A comparison of average metal concentrations in the test and mantle body of P. nigra between two stations showed that the enrichment of V, Cd, Pb, Cu and Hg in the Thoothukudi samples may be due to high bioaccumulation factors of these elements as compared to other species of ascidians. The bioaccumulation factors were in the order of V>Pb>Cd>Cu> Hg for the test and mantle body in stations 1 and 2. Application of one-way ANOVA for the concentration of these metals between test and mantle body showed significant differences in both stations. Similarly, ANOVA for biosorption of these trace metals by P. nigra showed significant difference between stations. Metal concentrations recorded in this ascidian could effectively be used as good reference material for monitoring metal contamination in Indian sea waters. Copyright © 2015 Elsevier Inc. All rights reserved.

DJ-1-dependent protective activity of DJ-1-binding compound no. 23 against neuronal cell death in MPTP-treated mouse model of Parkinson's disease

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Kazuko Takahashi-Niki

2015-03-01

Full Text Available Parkinson's disease (PD is caused by dopaminergic cell death in the substantia nigra, leading to a reduced level of dopamine in the striatum. Oxidative stress is one of the causes of PD. Since symptomatic PD therapies are used, identification of compounds or proteins that inhibit oxidative stress-induced neuronal cell death is necessary. DJ-1 is a causative gene product of familial PD and plays a role in anti-oxidative stress reaction. We have identified various DJ-1-binding compounds, including compound-23, that restored neuronal cell death and locomotion defects observed in neurotoxin-induced PD models. In this study, wild-type and DJ-1-knockout mice were injected intraperitoneally with 1 mg/kg of compound-23 and then with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP at 1 h after injection. Five days after administration, the effects of compound-23 on MPTP-induced locomotion deficits, on dopaminergic cell death and on brain dopamine levels were analyzed by rotor rod tests, by staining cells with an anti-TH antibody and by an HPLC, respectively. The results showed that compound-23 inhibited MPTP-induced reduction of retention time on the rotor rod bar, neuronal cell death in the substantia nigra and striatum and dopamine content in wild-type mice but not in DJ-1-knockout mice, indicating a DJ-1-dependent effect of compound-23.

Sex and laterality differences in parkinsonian impairment and transcranial ultrasound in never-treated schizophrenics and their first degree relatives in an Andean population.

Science.gov (United States)

Kamis, Danielle; Stratton, Lee; Calvó, María; Padilla, Eduardo; Florenzano, Néstor; Guerrero, Gonzalo; Molina Rangeon, Beatriz; Molina, Juan; de Erausquin, Gabriel A

2015-05-01

We tested the hypothesis that loss of substantia nigra neurons in subjects at risk of schizophrenia (1), as reflected by midbrain hyperechogenicity (2) and parkinsonian motor impairment (3), is asymmetric and influenced by sex. We evaluated 62 subjects with never-treated chronic schizophrenia, 80 of their adult, unaffected first degree relatives and 62 healthy controls (matched by sex and age to the cases), part of an Andean population of Northern Argentina. Parkinsonism was scored blindly using UPDRS-3 (Unified Parkinson's Disease Rating Scale) on videotaped exams by 2 independent raters. Transcranial ultrasound was performed by an expert sonographist blind to subject condition with a 2.5 MHz transducer through a temporal bone window. Quantification of echogenic area was carried out on saved images by a different evaluator. We found a significant difference in parkinsonian motor impairment between patients, their relatives as well as controls. All three groups showed worse parkinsonism on the left side than the right, corresponding with increased echogenicity on the right substantia nigra compared with the left. Females had significantly more right echogenicity than males, and patients and unaffected relatives were significantly more echogenic than controls on that side. On the left, only female patients had significant echogenicity. Our data supports the notion that unaffected relatives of schizophrenic subjects have increased parkinsonism and concomitant brainstem abnormalities which may represent a vulnerability to the disease. Both motor and brainstem abnormalities are asymmetric and influenced by sex. Copyright © 2015 Elsevier B.V. All rights reserved.

Who Can Diagnose Parkinson's Disease First? Role of Pre-motor Symptoms.

Science.gov (United States)

Rodríguez-Violante, Mayela; Zerón-Martínez, Rosalía; Cervantes-Arriaga, Amin; Corona, Teresa

2017-04-01

In 1817, James Parkinson described the disease which bears his name. The disease was defined as a neurological syndrome characterized by tremor, rigidity, and slowness of movements. Almost one hundred years later, degeneration of neurons in the substantia nigra and low levels of dopamine were identified as the putative cause of the disease, thus the disease remained as a pure neurological disorder. In the late 1990s, non-motor symptoms of the disease began to gain interest because of their clinical relevance, as well as for their potential role in broadening the understanding of the pathophysiological mechanisms involved. In the last decade, focus has shifted to the pre-motor symptoms, those non-motor symptoms that present years before the motor onset of the disease. The main premotor symptoms include rapid eye movement sleep behavior disorder, hyposmia, constipation and depression. Subjects with these symptoms usually are not initially seen by a neurologist, and by the time they are consulted neuronal loss in the substantia nigra is over 50%. This review summarizes the overall relevance of non-motor symptoms, their frequency and their pathophysiological implications. Also, the importance of pre-motor symptoms, and the role of specialists other than neurologists in diagnosing subjects with Parkinson's disease is discussed. Two hundred years after the first description of the disease, it is now evident that Parkinson's disease is a systemic disease and a multispecialty team approach is mandatory. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

Property of lysosomal storage disease associated with midbrain pathology in the central nervous system of Lamp-2-deficient mice.

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Furuta, Akiko; Kikuchi, Hisae; Fujita, Hiromi; Yamada, Daisuke; Fujiwara, Yuuki; Kabuta, Tomohiro; Nishino, Ichizo; Wada, Keiji; Uchiyama, Yasuo

2015-06-01

Lysosome-associated membrane protein-2 (LAMP-2) is the gene responsible for Danon disease, which is characterized by cardiomyopathy, autophagic vacuolar myopathy, and variable mental retardation. To elucidate the function of LAMP-2 in the central nervous system, we investigated the neuropathological changes in Lamp-2-deficient mice. Immunohistochemical observations revealed that Lamp-1 and cathepsin D-positive lysosomal structures increased in the large neurons of the mouse brain. Ubiquitin-immunoreactive aggregates and concanavalin A-positive materials were detected in these neurons. By means of ultrastructural studies, we found various-shaped accumulations, including lipofuscin, glycolipid-like materials, and membranous structures, in the neurons and glial cells of Lamp-2-deficient brains. In deficient mice, glycogen granules accumulated in hepatocyte lysosomes but were not observed in neurons. These pathological features indicate lysosomal storage disease; however, the findings are unlikely a consequence of deficiency of a single lysosomal enzyme. Although previous study results have shown a large amount of autophagic vacuoles in parenchymal cells of the visceral organs, these findings were rarely detected in the brain tissue except for some axons in the substantia nigra, in which abundant activated microglial cells with increased lipid peroxidation were observed. Thus, LAMP-2 in the central nervous system has a possible role in the degradation of the various macromolecules in lysosomes and an additional function concerning protection from oxidative stress, especially in the substantia nigra. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities

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Maekawa Tatsunori

2012-04-01

Full Text Available Abstract Background Leucine-rich repeat kinase 2 (LRRK2 is the gene responsible for autosomal-dominant Parkinson’s disease (PD, PARK8, but the mechanism by which LRRK2 mutations cause neuronal dysfunction remains unknown. In the present study, we investigated for the first time a transgenic (TG mouse strain expressing human LRRK2 with an I2020T mutation in the kinase domain, which had been detected in the patients of the original PARK8 family. Results The TG mouse expressed I2020T LRRK2 in dopaminergic (DA neurons of the substantia nigra, ventral tegmental area, and olfactory bulb. In both the beam test and rotarod test, the TG mice exhibited impaired locomotive ability in comparison with their non-transgenic (NTG littermates. Although there was no obvious loss of DA neurons in either the substantia nigra or striatum, the TG brain showed several neurological abnormalities such as a reduced striatal dopamine content, fragmentation of the Golgi apparatus in DA neurons, and an increased degree of microtubule polymerization. Furthermore, the tyrosine hydroxylase-positive primary neurons derived from the TG mouse showed an increased frequency of apoptosis and had neurites with fewer branches and decreased outgrowth in comparison with those derived from the NTG controls. Conclusions The I2020T LRRK2 TG mouse exhibited impaired locomotive ability accompanied by several dopaminergic neuron abnormalities. The TG mouse should provide valuable clues to the etiology of PD caused by the LRRK2 mutation.

Nigral dopaminergic neuron replenishment in adult mice through VE-cadherin-expressing neural progenitor cells

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Abir A Rahman

2017-01-01

Full Text Available The function of dopaminergic neurons in the substantia nigra is of central importance to the coordination of movement by the brain's basal ganglia circuitry. This is evidenced by the loss of these neurons, resulting in the cardinal motor deficits associated with Parkinson's disease. In order to fully understand the physiology of these key neurons and develop potential therapies for their loss, it is essential to determine if and how dopaminergic neurons are replenished in the adult brain. Recent work has presented evidence for adult neurogenesis of these neurons by Nestin+/Sox2– neural progenitor cells. We sought to further validate this finding and explore a potential atypical origin for these progenitor cells. Since neural progenitor cells have a proximal association with the vasculature of the brain and subsets of endothelial cells are Nestin+, we hypothesized that dopaminergic neural progenitors might share a common cell lineage. Therefore, we employed a VE-cadherin promoter-driven CREERT2:THlox/THlox transgenic mouse line to ablate the tyrosine hydroxylase gene from endothelial cells in adult animals. After 26 weeks, but not 13 weeks, following the genetic blockade of tyrosine hydroxylase expression in VE-cadherin+ cells, we observed a significant reduction in tyrosine hydroxylase+ neurons in the substantia nigra. The results from this genetic lineage tracing study suggest that dopaminergic neurons are replenished in adult mice by a VE-cadherin+ progenitor cell population potentially arising from an endothelial lineage.

Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis.

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Sadasivan, Shankar; Sharp, Bridgett; Schultz-Cherry, Stacey; Smeyne, Richard Jay

2017-01-01

Central Nervous System inflammation has been implicated in neurodegenerative disorders including Parkinson's disease (Ransohoff, Science 353: 777-783, 2016; Kannarkat et al. J. Parkinsons Dis. 3: 493-514, 2013). Here, we examined if the H1N1 influenza virus (Studahl et al. Drugs 73: 131-158, 2013) could synergize with the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (Jackson-Lewis et al. in Mark LeDoux (ed) Movement Disorders: Genetics and Models : 287-306, Elsevier, 2015) to induce a greater microglial activation and loss of substantia nigra pars compacta dopaminergic neurons than either insult alone. H1N1-infected animals administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exhibit a 20% greater loss of substantia nigra pars compacta dopaminergic neurons than occurs from the additive effects of H1N1 or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine alone ( p  effects were found in microglial activation. The synergistic dopaminergic neuron loss is eliminated by influenza vaccination or treatment with oseltamivir carboxylate. This work shows that multiple insults can induce synergistic effects; and even these small changes can be significant as it might allow one to cross a phenotypic disease threshold that would not occur from individual non-interacting exposures. Our observations also have important implications for public health, providing impetus for influenza vaccination or prompt treatment with anti-viral medications upon influenza diagnosis.

Presymptomatic detection of Parkinson's disease.

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Jenner, P

1993-01-01

Presymptomatic detection of Parkinson's disease is necessary if neuroprotective therapies are to be utilized in its treatment. Various methods (PET, electrophysiology, enzyme assays, olfactory function) may be applicable but none has been rigorously evaluated. Other possible approaches are now considered. Plasma HVA levels (pHVA) in the presence of debrisoquine may reflect cerebral dopamine function. However, there are no detectable differences in pHVA between newly diagnosed and untreated parkinsonian patients and control subjects. Compensatory increases in dopamine turnover may mask a decrease in pHVA in the early stages of the disease. So, at present this technique could not be used as a diagnostic tool. Post-mortem studies of brain in Parkinson's disease may provide clues to biochemical markers indicative of nigral pathology. Mitochondrial complex I activity is reduced in substantia nigra in Parkinson's disease and it was reported also to be markedly reduced in blood platelets. However, subsequent studies suggest that the difference in platelet complex I activity is too small to be diagnostic of Parkinson's disease. There are also selective reductions in brain glutathione levels in Parkinson's disease restricted to substantia nigra, which do not occur in other neurodegenerative disorders and are not due to drug treatment. Importantly, in incidental Lewy body disease (preclinical Parkinson's disease) nigral glutathione levels are reduced to the same degree as in advanced Parkinson's disease. So, some peripheral index of altered glutathione function may be valuable in the early detection of the disease process.

Ketogenic diet metabolites reduce firing in central neurons by opening K(ATP) channels.

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Ma, Weiyuan; Berg, Jim; Yellen, Gary

2007-04-04

A low-carbohydrate ketogenic diet remains one of the most effective (but mysterious) treatments for severe pharmacoresistant epilepsy. We have tested for an acute effect of physiological ketone bodies on neuronal firing rates and excitability, to discover possible therapeutic mechanisms of the ketogenic diet. Physiological concentrations of ketone bodies (beta-hydroxybutyrate or acetoacetate) reduced the spontaneous firing rate of neurons in slices from rat or mouse substantia nigra pars reticulata. This region is thought to act as a "seizure gate," controlling seizure generalization. Consistent with an anticonvulsant role, the ketone body effect is larger for cells that fire more rapidly. The effect of ketone bodies was abolished by eliminating the metabolically sensitive K(ATP) channels pharmacologically or by gene knock-out. We propose that ketone bodies or glycolytic restriction treat epilepsy by augmenting a natural activity-limiting function served by K(ATP) channels in neurons.

Faciobrachial dystonic seizures result from fronto-temporo-basalganglial network involvement.

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Iyer, Rajesh Shankar; Ramakrishnan, T C R; Karunakaran; Shinto, Ajit; Kamaleshwaran, Koramadai Karuppuswamy

2017-01-01

•Faciobrachial dystonic seizures (FBDS) are caused by autoantibodies to leucine-rich glioma-inactivated1 proteins, a component of the voltage-gated potassium channel complex (VGKC-complex) and precede the clinical presentation of limbic encephalitis.•The exact pathophysiology of FBDS is not known and whether they are seizures or movement disorder is still debated.•We suggest the fronto-temporo-basal ganglia network involving the medial frontal and temporal regions along with the corpus striatum and substantia nigra being responsible for the clinical phenomenon of FBDS.•The varied clinical, electrical and imaging features of FBDS in our cases and in the literature are best explained by involvement of this network.•Entrainment from any part of this network will result in similar clinical expression of FBDS, whereas other electro-clinical associations and duration depends on the extent of involvement of the network.

Mechanism by Sambucus nigra Extract Improves Bone Mineral Density in Experimental Diabetes

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Laurentiu Badescu

2012-01-01

Full Text Available The effects of polyphenols extracted from Sambucus nigra fruit were studied in streptozotocin- (STZ- induced hyperglycemic rats to evaluate its possible antioxidant, anti-inflammatory, antiglycosylation activity, and antiosteoporosis effects in diabetes. DEXA bone mineral density tests were performed in order to determine bone mineral density (BMD, bone mineral content (BMC, and fat (%Fat in control and diabetic animals, before and after polyphenol delivery. As compared to the normoglycemic group, the rats treated with STZ (60 mg/kg body weight revealed a significant malondialdehyde (MDA increase, as an index of the lipid peroxidation level, by 69%, while the total antioxidant activity (TAS dropped by 36%, with a consistently significant decrease (<0.05 in the activity of superoxide dismutase (SOD and glutathione peroxidase (GPX. Also, the treatment of rats with STZ revealed a significant increase of IL-6, glycosylated haemoglobin (HbA1c, and osteopenia detected by DEXA bone mineral density tests. The recorded results highlight a significant improvement (<0.001 in the antioxidative capacity of the serum in diabetic rats treated with natural polyphenols, bringing back to normal the concentration of reduced glutathione (GSH, as well as an important decrease in the serum concentration of MDA, with improved osteoporosis status. Knowing the effects of polyphenols could lead to the use of the polyphenolic extract of Sambucus nigra as a dietary supplement in diabetic osteoporosis.

New strategies for the treatment of Parkinson's disease hold considerable promise for future management of neurodegenerative disorders

DEFF Research Database (Denmark)

Bjarkam, Carsten Reidies; Sørensen, Jens Christian; Sunde, Niels Å

2001-01-01

or more. Parkinson's disease ischaracterized by a massive loss of dopaminergicneurons in the substantia nigra, leading tosevere functional disturbance of the neuronalcircuitry in the basal ganglia. A thoroughdescription of basal ganglia circuitry inhealth and disease is presented. We describehow...... the functional disturbances seen inParkinson's disease may be corrected atspecific sites in this circuitry by medicaltreatment or, in advanced stages of Parkinson'sdisease, by neurosurgical methods. The latterinclude lesional surgery, neuraltransplantation and deep brain stimulation,together with future...... in otherneurodegenerative diseases are discussed, withspecial emphasis on deep brain stimulation....

Direct gene transfer in the Gottingen minipig CNS using stereotaxic lentiviral microinjections

DEFF Research Database (Denmark)

GLUD, AN; Hedegaard, Claus; Nielsen, Mette Slot

2010-01-01

We aim to induce direct viral mediated gene transfer in the substantia nigra (SN) of the Gottingen minipig using MRI guided stereotaxic injections of lentiviral vectors encoding enhanced green fluorescent protein (EGFP). Nine female Gottingen minipigs were injected unilaterally into the SN with 6...... per 2.5 microliters lentivirus capable of transducing cells and mediating expression of recombinant EGFP. The animals were euthanized after four (n=3) or twenty weeks (n=6). Fresh brain tissue from three animals was used for PCR. The remaining six brains were cryo- or paraffin...

Clinical Application of 18F-FDG PET in Parkinson's Disease

International Nuclear Information System (INIS)

Lee, Won Hyoung; Chung, Yong An

2008-01-01

Parkinson's disease is the second most common neurodegenerative disorder. It is slowly progressive disease that affects a small area of cells in the mid brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in a vital chemical known as dopamine. In the diagnosis of Parkinson's disease, it has difficulty in biopsy and limits in radiologic modalities. 18F-FDG PET shows various findings from normal to diffuse decrement of FDG uptake. 18 F-FDG PET is expected to be a evaluation tool in the treatment of Parkinson's disease

Clinical and neuropathological findings of acute carbon monoxide toxicity in chihuahuas following smoke inhalation.

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Kent, Marc; Creevy, Kate E; Delahunta, Alexander

2010-01-01

Three adult Chihuahuas were presented for evaluation after smoke inhalation during a house fire. All three dogs received supportive care and supplemental oxygen. After initial improvement, the dogs developed seizures. Despite anticonvulsant therapy and supportive care, the dogs died. The brains of two dogs were examined. Lesions were identified that were compatible with acute carbon monoxide (CO) toxicity. Lesions were confined to the caudate nucleus, the globus pallidus, and the substantia nigra bilaterally, as well as the cerebellum, cerebral cortex, and dorsal thalamus. This case report describes the clinicopathological sequelae in acute CO toxicity.

Molecular Gerontology: Principles and Perspectives for Interventions

DEFF Research Database (Denmark)

Rattan, Suresh

2014-01-01

Research has clearly established a link between omega-3 fatty acids and general health, particularly cardiovascular health. Omega-3 Fatty Acids in Brain and Neurological Health is the first book to focus exclusively on the role of omega-3 fatty acids on general brain health. The articles...... some of the most recent research, including the role of omega-3 fatty acid supplements on hippocampal neurogenesis, substantia nigra modulation, migraine headaches, the developing brain in animals, sleep, and neurodegenerative diseases. This collection helps to push research forward toward a complete...

Efecto de la pérdida de la inervación dopaminérgica del núcleo subtalámico sobre la conducta motora de ratas

OpenAIRE

Nancy Pavón-Fuentes; Lisette Blanco-Lezcano; Lourdes Lorigados-Pedre; Lázaro Álvarez-González; Lisis Martínez-Martí; Raúl Macías-González

2010-01-01

Actualmente la enfermedad de Parkinson es considerada como un trastorno del sistema nervioso central que afecta a los ganglios basales. Las características anatomopatológicas más prominentes de esta enfermedad son: degeneración de las células dopaminérgicas de la substantia nigra pars compacta (SNc), la existencia de gliosis y la presencia de cuerpos eosinófilos de inclusión. La relevancia fisiológica de la modulación directa de las neuronas del núcleo subtalámico (NST) por neuronas dopaminér...

EL NÚCLEO PEDUNCULOPONTINO Y SU RELACIÓN CON LA FISIOPATOLOGÍA DE LA ENFERMEDAD DE PARKINSON

OpenAIRE

LISETTE BLANCO LEZCANO; LOURDES LORIGADOS PEDRÉ; TERESA SERRANO SÁNCHEZ; NANCY PAVÓN FUENTES; MA. ELENA GONZÁLEZ; LILIANA FRANCIS TURNER

2012-01-01

Varias décadas de investigaciones neuropatológicas e imagenológicas han proporcionado suficientes evidencias acerca de las alteraciones en la neurotransmisión colinérgica que acompañan a la disfunción dopaminérgica en la enfermedad de Parkinson (EP). El núcleo pedunculopontino tegmental laterodorsal (NPP) representa una de las fuentes principales de proyecciones colinérgicas en el cerebro y a su vez es el origen de la única proyección colinérgica que recibe la substantia nigra pars compacta (...

MRI in Parkinson's disease and vascular Parkinsonism

International Nuclear Information System (INIS)

Aotsuka, Akiyo; Shinotoh, Hitoshi; Hirayama, Keizo; Ikehira, Hiroo; Fukuda, Hiroshi.

1991-01-01

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.)

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

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Jackalina M Van Kampen

olfactory bulb, then the striatum, the substantia nigra and, finally, hippocampal and cortical regions. The slowly progressive nature of this model, together with its construct, face and predictive validity, make it ideal for the screening of potential neuroprotective therapies for the treatment of PD.

The development of hyperhydric tissue on the stems of Sambucus nigra L.

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Jadwiga A. Tarkowska

2014-01-01

Full Text Available Hyperhydric intumescences on the stems of Sambucus nigra arise in places where the stem lenticels are immersed in water. The hyperhydric tissue develops through the transformation of the multilayered phelloderm, the parenchyma of the cortex. endodermis and pericycle. The phellogen loses its meristematic properties and is either incorporated into the developing hyperhydric tissue or crushed. The succesive stages of hyperhydric changes which depend on the intense growth of cells and on the ability to devide acquired by them are presented.

Effect of variety on content of bioactive phenolic compounds in common elder (Sambucus nigra L.)

Czech Academy of Sciences Publication Activity Database

Vrchotová, Naděžda; Dadáková, E.; Matějíček, A.; Tříska, Jan; Kaplan, J.

2017-01-01

Roč. 31, č. 6 (2017), s. 700-703 ISSN 1478-6419 R&D Projects: GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : Sambucus nigra * flavonoids * phenolic acids * HPLC-MS Subject RIV: EH - Ecology, Behaviour OBOR OECD: Environmental sciences (social aspects to be 5.7) Impact factor: 1.828, year: 2016

A New Record of Chaunocephalus ferox (Digenea, Echinostomatidae from Ciconia nigra in Ukraine Including Morphological and Molecular Data

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Greben О. B.

2016-04-01

Full Text Available Morphological and molecular data on the type-species of Chaunocephalus Dietz, 1910, Chaunocephalus ferox (Rudolphi, 1795 is provided based on material collected from the type-host, Ciconia nigra (Linnaeus, from Kiev Zoo, Ukraine.

High affinity hemoglobin and Parkinson's disease.

Science.gov (United States)

Graham, Jeffrey; Hobson, Douglas; Ponnampalam, Arjuna

2014-12-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain. Oxidative damage in this region has been shown to play an important role in the pathogenesis of this disease. Human neurons have been discovered to contain hemoglobin, with an increased concentration seen in the neurons of the SN. High affinity hemoglobin is a clinical entity resulting from mutations that create a functional increase in the binding of hemoglobin to oxygen and an inability to efficiently unload it to tissues. This can result in a number of metabolic compensatory changes, including an elevation in circulating hemoglobin and an increase in the molecule 2,3-diphosphoglycerate (2,3-DPG). Population based studies have revealed that patients with PD have elevated hemoglobin as well as 2,3-DPG levels. Based on these observations, we hypothesize that the oxidative damage seen in PD is related to an underlying high affinity hemoglobin subtype. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dense genetic linkage maps of three Populus species (Populus deltoides, P. nigra and P. trichocarpa) based on AFLP and microsatellite markers.

Science.gov (United States)

Cervera, M T; Storme, V; Ivens, B; Gusmão, J; Liu, B H; Hostyn, V; Van Slycken, J; Van Montagu, M; Boerjan, W

2001-06-01

Populus deltoides, P. nigra, and P. trichocarpa are the most important species for poplar breeding programs worldwide. In addition, Populus has become a model for fundamental research on trees. Linkage maps were constructed for these three species by analyzing progeny of two controlled crosses sharing the same female parent, Populus deltoides cv. S9-2 x P. nigra cv. Ghoy and P. deltoides cv. S9-2 x P. trichocarpa cv. V24. The two-way pseudotestcross mapping strategy was used to construct the maps. Amplified fragment length polymorphism (AFLP) markers that segregated 1:1 were used to form the four parental maps. Microsatellites and sequence-tagged sites were used to align homoeologous groups between the maps and to merge linkage groups within the individual maps. Linkage analysis and alignment of the homoeologous groups resulted in 566 markers distributed over 19 groups for P. deltoides covering 86% of the genome, 339 markers distributed over 19 groups for P. trichocarpa covering 73%, and 369 markers distributed over 28 groups for P. nigra covering 61%. Several tests for randomness showed that the AFLP markers were randomly distributed over the genome.

Chemical Composition of Ballota macedonica Vandas and Ballota nigra L. ssp. foetida (Vis.) Hayek Essential Oils - The Chemotaxonomic Approach.

Science.gov (United States)

Đorđević, Aleksandra S; Jovanović, Olga P; Zlatković, Bojan K; Stojanović, Gordana S

2016-06-01

The essential oils isolated from fresh aerial parts of Ballota macedonica (two populations) and Ballota nigra ssp. foetida were analyzed by GC and GC/MS. Eighty five components were identified in total; 60 components in B. macedonica oil (population from the Former Yugoslav Republic of Macedonia), 34 components in B. macedonica oil (population from the Republic of Serbia), and 33 components in the oil of B. nigra ssp. foetida accounting for 93.9%, 98.4%, and 95.8% of the total oils, respectively. The most abundant components in B. macedonica oils were carotol (13.7 - 52.1%), germacrene D (8.6 - 24.6%), and (E)-caryophyllene (6.5 - 16.5%), while B. nigra ssp. foetida oil was dominated by (E)-phytol (56.9%), germacrene D (10.0%), and (E)-caryophyllene (4.7%). Multivariate statistical analyses (agglomerative hierarchical cluster analysis and principal component analysis) were used to compare and discuss relationships among Ballota species examined so far based on their volatile profiles. The chemical compositions of B. macedonica essential oils are reported for the first time. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Fast Na+ spike generation in dendrites of guinea-pig substantia nigra pars compacta neurons

DEFF Research Database (Denmark)

Nedergaard, S; Hounsgaard, Jørn Dybkjær

1996-01-01

were not inhibited in the presence of glutamate receptor antagonists or during Ca2+ channel blockade. Blockers of gap junctional conductance (sodium propionate, octanol and halothane) did not affect the field-induced spikes. The spike generation was highly sensitive to changes in membrane conductance...

First report of Geosmithia morbida on ambrosia beetles emerged from thousand cankers-diseased Juglans nigra in Ohio

Science.gov (United States)

Jennifer Juzwik; M. McDermott-Kubeczko; T. J. Stewart; M. D. Ginzel

2016-01-01

Eastern black walnut (Juglans nigra) is a highly-valued species for timber and nut production in the eastern United States. Thousand cankers disease (TCD), caused by the interaction of the walnut twig beetle (Pityophthorus juglandis) and the canker fungus Geosmithia morbida (Tisserat et al. 2009), was first...

Morphological, biochemical and sensory characteristics of black mulberry fruits (Morus nigra L.)

OpenAIRE

Beáta Stehlíková; Marcela Čuláková; Andrej Sinica; Lucia Kucelová; Ján Brindza

2013-01-01

This work aimed at the morphological, biochemical, technological and sensorial determination of black mulberry (Morus nigra L. – MN)  fruitage and their utilization in the food production branches. For the experimental purposes were selected 50 genotypes of this population grown in the Pukanec surroundings. The medium fruitage weight determined in the selected collection ranged from 7.26 g (MN-1) to 1.42 g (MN-14), fruitage length in a range of 13.51 mm (MN-14) to 29.20 mm (MN-12) and the med...

A well-refined in vitro model derived from human embryonic stem cell for screening phytochemicals with midbrain dopaminergic differentiation-boosting potential for improving Parkinson's disease.

Science.gov (United States)

Hsieh, Wen-Ting; Chiang, Been-Huang

2014-07-09

Stimulation of endogenous neurogenesis is a potential approach to compensate for loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in patients with Parkinson's disease (PD). This objective was to establish an in vitro model by differentiating pluripotent human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA neurogenesis-boosting potentials. Consequently, a five-stage differentiation process was developed. The derived cells expressed many mDA markers including tyrosine hydroxylase (TH), β-III tubulin, and dopamine transporter (DAT). The voltage-gated ion channels and dopamine release were also examined for verifying neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then, several potential phytochemicals including green tea catechins and ginsenosides were tested using the model. Finally, ginsenoside Rb1 was identified as the most potent phytochemical which is capable of upregulating neurotrophin expression and inducing mDA differentiation.

Examination of correlation between histidine and nickel absorption by Morus L., Robinia pseudoacacia L. and Populus nigra L. using HPLC-MS and ICP-MS.

Science.gov (United States)

Ozen, Sukran Akkus; Yaman, Mehmet

2016-08-02

In this study, HPLC-MS and ICP-MS methods were used for the determination of histidine and nickel in Morus L., Robinia pseudoacacia L., and Populus nigra L. leaves taken from industrial areas including Gaziantep and Bursa cities. In the determination of histidine by HPLC-MS, all of the system parameters such as flow rate of mobile phase, fragmentor potential, injection volume and column temperature were optimized and found to be 0.2 mL min(-1), 70 V, 15 µL, and 20°C, respectively. Under the optimum conditions, histidine was extracted from plant sample by distilled water at 90°C for 30 min. Concentrations of histidine as mg kg(-1) were found to be between 2-9 for Morus L., 6-13 for Robinia pseudoacacia L., and 2-10 for Populus nigra L. Concentrations of nickel were in the ranges of 5-10 mg kg(-1) for Morus L., 3-10 mg kg(-1) for Robinia pseudoacacia L., and 0.6-4 mg kg(-1) for Populus nigra L. A significant linear correlation (r = 0.78) between histidine and Ni was observed for Populus nigra L., whereas insignificant linear correlation for Robinia pseudoacacia L. (r = 0.22) were seen. Limits of detection (LOD) and quantitation (LOQ) were found to be 0.025 mg Ni L(-1) and 0.075 mg Ni L(-1), respectively.

Developing new microsatellite markers in walnut (Juglans regia L.) from Juglans nigra genomic GA enriched library

Science.gov (United States)

Hayat Topcu; Nergiz Coban; Keith Woeste; Mehmet Sutyemez; Salih. Kafkas

2015-01-01

We attempted to develop new polymorphic SSR primer pairs in walnut using sequences derived from Juglans nigra L. genomic enriched library with GA repeat. The designed 94 SSR primer pairs were subjected to gradient PCR in 12 walnut cultivars to determine their optimum annealing temperatures and to determine whether they produce bands. Then, the...

Geochemical peculiarities of black poplar leaves (Populus nigra L.) in the sites with heavy metals intensive fallouts

Science.gov (United States)

Yalaltdinova, Albina; Baranovskaya, Natalya; Rikhvanov, Leonid; Matveenko, Irina

2013-04-01

The article deals with the content of 28 chemical elements in the leaves ash of black poplar (Populus nigra L.) growing in Ust-Kamenogorsk city area. It is the major industrial center of Kazakhstan Republic on the territory where the industrial giants of non-ferrous metallurgy and nuclear energy are situated. Comparative analysis with the similar data obtained from leaves ash of Populus nigra L. in Tomsk, Ekibastuz, and Pavlodar cities has revealed that in comparison with other urban areas, leaves ash of black poplar (Populus nigra L.) from Ust-Kamenogorsk city is characterized by elevated concentration rates of Ta, U, Zn, Ag, As, Sb, Br, Sr and Na. Within the city, the sites and areas with abnormal contents of typomorphic pollutants have been revealed. In the central part of the city, in the vicinity of lead-zinc plant and Ulba metallurgical plant, the highest concentrations of Ta, U, Zn, Ag, Au, As, Sb, Cr and Fe were marked. In the northeast, where the titanium-magnesium plant is located, elevated concentrations of Br and Sr were stated. Thus, the impact of major city enterprises which are the main sources of heavy metals is reflected in the element composition. Zn, As, Sb, Ag and Au comes from lead-zinc plant and its refinery plants, while Ulba metallurgical plant can be considered source of Ta and U in the environment, producing tantalum and fuel pellets for nuclear power plants. These companies, due to the current objective circumstances, are located in the central part of the city, have a significant negative effect on the environment and form the risk factors for human health.

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

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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).

The dual orexin/hypocretin receptor antagonist, almorexant, in the ventral tegmental area attenuates ethanol self-administration.

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Subhashini Srinivasan

Full Text Available Recent studies have implicated the hypocretin/orexinergic system in reward-seeking behavior. Almorexant, a dual orexin/hypocretin R(1 and R(2 receptor antagonist, has proven effective in preclinical studies in promoting sleep in animal models and was in Phase III clinical trials for sleep disorders. The present study combines behavioral assays with in vitro biochemical and electrophysiological techniques to elucidate the role of almorexant in ethanol and sucrose intake. Using an operant self-administration paradigm, we demonstrate that systemic administration of almorexant decreased operant self-administration of both 20% ethanol and 5% sucrose. We further demonstrate that intra-ventral tegmental area (VTA infusions, but not intra-substantia nigra infusions, of almorexant reduced ethanol self-administration. Extracellular recordings performed in VTA neurons revealed that orexin-A increased firing and this enhancement of firing was blocked by almorexant. The results demonstrate that orexin/hypocretin receptors in distinct brain regions regulate ethanol and sucrose mediated behaviors.

Dopaminergic Neuron-Specific Deletion of p53 Gene Attenuates Methamphetamine Neurotoxicity.

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Lu, Tao; Kim, Paul P; Greig, Nigel H; Luo, Yu

2017-08-01

p53 plays an essential role in the regulation of cell death in dopaminergic (DA) neurons and its activation has been implicated in the neurotoxic effects of methamphetamine (MA). However, how p53 mediates MA neurotoxicity remains largely unknown. In this study, we examined the effect of DA-specific p53 gene deletion in DAT-p53KO mice. Whereas in vivo MA binge exposure reduced locomotor activity in wild-type (WT) mice, this was significantly attenuated in DAT-p53KO mice and associated with significant differences in the levels of the p53 target genes BAX and p21 between WT and DAT-p53KO. Notably, DA-specific deletion of p53 provided protection of substantia nigra pars reticulata (SNpr) tyrosine hydroxylase (TH) positive fibers following binge MA, with DAT-p53KO mice having less decline of TH protein levels in striatum versus WT mice. Whereas DAT-p53KO mice demonstrated a consistently higher density of TH fibers in striatum compared to WT mice at 10 days after MA exposure, DA neuron counts within the substantia nigra pars compacta (SNpc) were similar. Finally, supportive of these results, administration of a p53-specific inhibitor (PFT-α) provided a similarly protective effect on MA binge-induced behavioral deficits. Neither DA specific p53 deletion nor p53 pharmacological inhibition affected hyperthermia induced by MA binge. These findings demonstrate a specific contribution of p53 activation in behavioral deficits and DA neuronal terminal loss by MA binge exposure.

The PPARgamma agonist pioglitazone is effective in the MPTP mouse model of Parkinson's disease through inhibition of monoamine oxidase B.

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Quinn, L P; Crook, B; Hows, M E; Vidgeon-Hart, M; Chapman, H; Upton, N; Medhurst, A D; Virley, D J

2008-05-01

The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist pioglitazone has previously been shown to attenuate dopaminergic cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease, an effect attributed to its anti-inflammatory properties. In the present investigation, we provide evidence that pioglitazone is effective in the MPTP mouse model, not via an anti-inflammatory action, but through inhibition of MAO-B, the enzyme required to biotransform MPTP to its active neurotoxic metabolite 1-methyl-4-phenylpyridinium (MPP+). Mice were treated with pioglitazone (20 mg kg(-1) b.i.d. (twice a day), p.o., for 7 days), prior and post or post-MPTP (30 mg kg(-1) s.c.) treatment. Mice were then assessed for motor impairments on a beam-walking apparatus and for reductions in TH immunoreactivity in the substantia nigra and depletions in striatal dopamine. The effects of pioglitazone on striatal MPP+ levels and MAO-B activity were also assessed. Mice treated with MPTP showed deficits in motor performance, marked depletions in striatal dopamine levels and a concomitant reduction in TH immunoreactivity in the substantia nigra. Pretreatment with pioglitazone completely prevented these effects of MPTP. However, pretreatment with pioglitazone also significantly inhibited the MPTP-induced production of striatal MPP+ and the activity of MAO-B in the striatum. The neuroprotection observed with pioglitazone pretreatment in the MPTP mouse model was due to the blockade of the conversion of MPTP to its active toxic metabolite MPP+, via inhibition of MAO-B.

Diffusion tensor imaging of the nigrostriatal fibers in Parkinson's disease.

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Zhang, Yu; Wu, I-Wei; Buckley, Shannon; Coffey, Christopher S; Foster, Eric; Mendick, Susan; Seibyl, John; Schuff, Norbert

2015-08-01

Parkinson's disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars compacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregulation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to 1) develop a diffusion tensor tractography protocol for reliably tracking the nigrostriatal fibers on multicenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; and 3) test whether abnormal integrities of the nigrostriatal fibers in PD patients are associated with the severity of motor disability and putaminal dopamine binding ratios. Diffusion tensor tractography was performed on 50 drug-naïve PD patients and 27 healthy control subjects from the international multicenter Parkinson's Progression Marker Initiative. Tractography consistently detected the nigrostriatal fibers, yielding reliable diffusion measures. Fractional anisotropy, along with radial and axial diffusivity of the nigrostriatal tract, showed systematic abnormalities in patients. In addition, variations in fractional anisotropy and radial diffusivity of the nigrostriatal tract were associated with the degree of motor deficits in PD patients. Taken together, the findings imply that the diffusion tensor imaging characteristic of the nigrostriatal tract is potentially an index for detecting and staging of early PD. © 2015 International Parkinson and Movement Disorder Society.

Renin angiotensin system and gender differences in dopaminergic degeneration

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Rodriguez-Perez Ana I

2011-08-01

Full Text Available Abstract Background There are sex differences in dopaminergic degeneration. Men are approximately two times as likely as premenopausal women of the same age to develop Parkinson's disease (PD. It has been shown that the local renin angiotensin system (RAS plays a prominent role in sex differences in the development of chronic renal and cardiovascular diseases, and there is a local RAS in the substantia nigra and dopaminergic cell loss is enhanced by angiotensin via type 1 (AT1 receptors. Results In the present study, we observed that intrastriatal injection of 6-hydroxydopamine induced a marked loss of dopaminergic neurons in the substantia nigra of male rats, which was significantly higher than the loss induced in ovariectomized female rats given estrogen implants (i.e. rats with estrogen. However, the loss of dopaminergic neurons was significantly lower in male rats treated with the AT1 antagonist candesartan, and similar to that observed in female rats with estrogen. The involvement of the RAS in gender differences in dopaminergic degeneration was confirmed with AT1a-null mice lesioned with the dopaminergic neurotoxin MPTP. Significantly higher expression of AT1 receptors, angiotensin converting enzyme activity, and NADPH-oxidase complex activity, and much lower levels of AT2 receptors were observed in male rats than in female rats with estrogen. Conclusions The results suggest that brain RAS plays a major role in the increased risk of developing PD in men, and that manipulation of brain RAS may be an efficient approach for neuroprotective treatment of PD in men, without the feminizing effects of estrogen.

Nigrosome-1 on Susceptibility Weighted Imaging to Differentiate Parkinson’s Disease From Atypical Parkinsonism: An In Vivo and Ex Vivo Pilot Study

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Meijer, Frederick J.A.; Steens, Stefan C.; Rumund, Anouke van; Cappellen van Walsum, Anne-Marie van; Küsters, Benno; Esselink, Rianne A.J.; Verbeek, Marcel M.; Bloem, Bastiaan R.; Goraj, Bożena

2016-01-01

Previous case-control studies have suggested that the absence of a swallow-tail appearance in the substantia nigra on high-resolution SWI, representing nigrosome-1, has high accuracy to identify Parkinson’s disease (PD). The first goal of our study was to evaluate nigrosome-1 ex vivo using optimized high-resolution susceptibility sensitive MRI. Our second goal was to evaluate its diagnostic value in vivo using a clinical 3T SWI sequence to differentiate between PD and atypical parkinsonism (AP) in a cohort of patients with early-stage parkinsonism. Case-control pilot study to evaluate nigrosome-1 ex vivo (2 PD, 2 controls), using high-resolution susceptibility sensitive sequences at 11.7 T MRI. Next, evaluation of nigrosome-1 in vivo using a clinical 3 T SWI sequence in a prospective cohort of 60 patients with early-stage parkinsonism (39 PD, 21 AP). Moreover, 12 control subjects were scanned. The bilateral substantia nigra was evaluated by two neuroradiologists for the presence, absence or indecisive presence of nigrosome-1. The discriminative power was evaluated by Receiver-Operating Characteristic. We identified nigrosome-1 in ex vivo control subjects. Nigrosome-1 was not identified in the ex vivo PD cases. In our prospective clinical cohort study, the AUC for the swallow-tail sign to discriminate between PD and AP was 0.56 (0.41–0.71) for reader 1 and 0.68 (0.55–0.82) for reader 2. The diagnostic accuracy of the swallow-tail sign was marginal to discriminate between PD and AP using our clinical 3 T SWI sequence

Prediction of Parkinson's disease subsequent to severe depression: a ten-year follow-up study.

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Walter, Uwe; Heilmann, Robert; Kaulitz, Lara; Just, Tino; Krause, Bernd Joachim; Benecke, Reiner; Höppner, Jacqueline

2015-06-01

Major depressive disorder (MDD) has been associated with an increased risk of subsequent Parkinson's disease (PD) in case-control and cohort studies. However, depression alone is unlikely to be a useful marker of prodromal PD due to its low specificity. In this longitudinal observational study, we assessed whether the presence of other potential markers of prodromal PD predicts the subsequent development of PD in MDD patients. Of 57 patients with severe MDD but no diagnosis of PD who underwent a structured interview, olfactory and motor investigation and transcranial sonography at baseline, 46 (36 women; mean age 54.9 ± 11.7 years) could be followed for up to 11 (median, 10) years. Three patients (2 women; age 64, 65 and 70 years) developed definite PD after 1, 7, and 9 years, respectively. The combined finding of mild asymmetric motor slowing, idiopathic hyposmia, and substantia nigra hyperechogenicity predicted subsequent PD in all patients who could be followed for longer than 1 year. Out of the whole study cohort, only the subjects with subsequent PD presented with the triad of asymmetric motor slowing, idiopathic hyposmia, and substantia nigra hyperechogenicity in combination with at least two out of four reportable risk factors (family history of PD, current non-smoker, non-coffee drinker, constipation) at baseline investigation. Post-hoc analysis revealed that additional rating of eye and eye-lid motor abnormalities might further improve the prediction of PD in larger cohorts. Findings of this pilot-study suggest that MDD patients at risk of subsequent PD can be identified using an inexpensive non-invasive diagnostic battery.

Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats.

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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.

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.

Degenerative pontine lesions in patients with familial narcolepsy.

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Stepień, Adam; Staszewski, Jacek; Domzał, Teofan M; Tomczykiewicz, Kazimierz; Skrobowska, Ewa; Durka-Kesy, Marta

2010-01-01

Narcolepsy is characterized by chronic excessive daytime sleepiness with episodic sleep attacks. There are several associated symptoms of narcolepsy: cataplexy (bilateral muscle weakness without loss of consciousness provoked by an emotional trigger, e.g. laughter), sleep paralysis and hypnagogic-hypnopompic hallucinations. Most cases are sporadic; familial narcolepsy contributes to only 1-5% of all cases. While most cases of narcolepsy are idiopathic and are not associated with clinical or radiographic evidence of brain pathology, symptomatic or secondary narcolepsy may occur occasionally in association with lesions caused by tumours, demyelination or strokes of the diencephalon, midbrain, and pons. There are some examples of non-specific brainstem lesions found in magnetic resonance imaging (MRI) in patients with idiopathic narcolepsy. The authors present eleven patients from a five-generation family with many members who suffer from episodic excessive daytime sleepiness. Narcolepsy was diagnosed in 9 patients. Sleepiness was frequently associated with cataplexy, hypnagogic-hypnopompic hallucinations and sleep paralysis. Improvement in their clinical state was observed during the treatment with modafinil. All probands had MRI of the brain, routine blood tests, EEG, polysomnography, examination of the level of hypocretin in cerebrospinal fluid and evaluation by means of Epworth and Stanford Sleepiness Scales. In 9 patients with narcolepsy, decreased thickness of the substantia nigra was found and in six of them degenerative lesions in the pontine substantia nigra were also noticed. The significance of these changes remains unclear. No data have been published until now concerning the presence of any brain lesions in patients with familial narcolepsy.

Utility of susceptibility-weighted MRI in differentiating Parkinson's disease and atypical parkinsonism

International Nuclear Information System (INIS)

Gupta, Deepak; Saini, Jitender; Kesavadas, Chandrasekharan; Sarma, P.S.; Kishore, Asha

2010-01-01

Neuropathological studies report varying patterns of brain mineralization in Parkinson's diseases (PD), progressive supranuclear palsy (PSP), and Parkinson variant of multiple system atrophy (MSA-P). Susceptibility-weighted imaging (SWI) is the ideal magnetic resonance imaging (MRI) technique to detect mineralization of the brain. The purpose of this study was to test if SWI can differentiate PD, PSP, and MSA-P. Eleven patients with PD, 12 with PSP, 12 with MSA-P, and 11 healthy controls underwent SWI of the brain. Hypointensity of putamen, red nucleus, substantia nigra, and dentate nucleus in all groups were measured using an objective grading scale and scored from 0 to 3. In PSP, hypointensity score of red nucleus was higher than that in MSA-P (p = 0.001) and PD (p = 0.001), and a score of ≥2 differentiated the PSP group from the PD and MSA-P groups. Putaminal hypointensity score was higher in PSP when compared to that in PD (p = 0.003), and a score of ≥2 differentiated PSP from PD groups. SWI hypointensity scores of red nucleus and putamen had an excellent intrarater and interrater correlation. Substantia nigra hypointensity score of the PSP group was higher than that of the MSA-P (p = 0.004) and PD (p = 0.006) groups, but the scores had only a moderate intrarater and interrater correlation. SWI shows different patterns of brain mineralization in clinically diagnosed groups of PD, PSP, and MSA-P and may be considered as an additional MR protocol to help differentiate these conditions. (orig.)

Pigmented Creatine Deposits in Amyotrophic Lateral Sclerosis Central Nervous System Tissues Identified by Synchrotron Fourier Transform Infrared Microspectroscopy and X-ray Fluorescence Spectromicroscopy

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Kastyak, M.; Szczerbowska-Boruchowska, M; Adamek, D; Tomik, B; Lankosz, M; Gough, K

2010-01-01

Amyotrophic Lateral Sclerosis (ALS) is an untreatable, neurodegenerative disease of motor neurons characterized by progressive muscle atrophy, limb paralysis, dysarthria, dysphagia, dyspnae and finally death. Large motor neurons in ventral horns of spinal cord and motor nuclei in brainstem, large pyramidal neurons of motor cortex and/or large myelinated axons of corticospinal tracts are affected. In recent synchrotron Fourier Transform Infrared microspectroscopy (sFTIR) studies of ALS CNS autopsy tissue, we discovered a small deposit of crystalline creatine, which has a crucial role in energy metabolism. We have now examined unfixed, snap frozen, post-autopsy tissue sections of motor cortex, brain stem, spinal cord, hippocampus and substantia nigra from six ALS and three non-degenerated cases with FTIR and micro-X-ray fluorescence (XRF). Heterogeneous pigmented deposits were discovered in spinal cord, brain stem and motor neuron cortex of two ALS cases. The FTIR signature of creatine has been identified in these deposits and in numerous large, non-pigmented deposits in four of the ALS cases. Comparable pigmentation and creatine deposits were not found in controls or in ALS hippocampus and substantia nigra. Ca, K, Fe, Cu and Zn, as determined by XRF, were not correlated with the pigmented deposits; however, there was a higher incidence of hot spots (Ca, Zn, Fe and Cu) in the ALS cases. The identity of the pigmented deposits remains unknown, although the absence of Fe argues against both erythrocytes and neuromelanin. We conclude that elevated creatine deposits may be indicators of dysfunctional oxidative processes in some ALS cases.

The stability of rutin and chlorogenic acid during the processing of black elder (Sambucus nigra) inflorescence

Czech Academy of Sciences Publication Activity Database

Dadáková, E.; Vrchotová, Naděžda; Chmelová, Š.; Šerá, Božena

2011-01-01

Roč. 40, č. 3 (2011), s. 327-334 ISSN 0139-3006 R&D Projects: GA ČR(CZ) GA525/05/2546 Institutional research plan: CEZ:AV0Z60870520 Keywords : black elder * Sambucus nigra L * rutin * chlorogenic acid * high-performance liquid chromatography * micellar electrokinetic chromatography Subject RIV: GM - Food Processing Impact factor: 0.444, year: 2011

Species verification of Dalbergia nigra and Dalbergia spruceana samples in the wood collection of the Forest Products Laboratory

Science.gov (United States)

Michael C. Wiemann; Edgard O. Espinoza

2017-01-01

To evade endangered timber species laws, unscrupulous importers sometimes attempt to pass protected Dalbergia nigra as look-alike but unprotected, Dalbergia Spruceana. Wood density and fluorescence properties are sometimes used to identify the species. Although these properties are useful and do not require special equipment,...

Assessment of extracts of Helichrysum arenarium, Crataegus monogyna, Sambucus nigra in photoprotective UVA and UVB; photostability in cosmetic emulsions.

Science.gov (United States)

Jarzycka, Anna; Lewińska, Agnieszka; Gancarz, Roman; Wilk, Kazimiera A

2013-11-05

The aim of our study was to investigate the photoprotective activity and photostability efficacy of sunscreen formulations containing Helichrysum arenarium, Sambucus nigra, Crataegus monogyna extracts and their combination. UV transmission of the emulsion films was performed by using diffuse transmittance measurements coupling to an integrating sphere. In vitro photoprotection and photostability efficacy were evaluated according to the following parameters: sun protection factor (SPF), UVA protection factor (PF-UVA), UVA/UVB ratio and critical wavelength (λc) before and after UV irradiation. The results obtained show that the formulations containing polyphenols fulfill the official requirements for sunscreen products due to their broad spectrum of UV protection combined with their high photostability and remarkable antioxidant properties. Therefore H. arenarium, S. nigra, C. monogyna extracts represent useful additives for cosmetic formulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Cerebral glucose metabolism in Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Martin, W R.W.; Beckman, J H; Calne, D B; Adam, M J; Harrop, R; Rogers, J G; Ruth, T J; Sayre, C I; Pate, B D [British Columbia Univ., Vancouver (Canada). TRIUMF Facility

1984-02-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

Brainstem pathology in spasmodic dysphonia

Science.gov (United States)

Simonyan, Kristina; Ludlow, Christy L.; Vortmeyer, Alexander O.

2009-01-01

Spasmodic dysphonia (SD) is a primary focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speech production. We examined two rare cases of postmortem brainstem tissue from SD patients compared to four controls. In SD patients, small clusters of inflammation were found in the reticular formation surrounding solitary tract, spinal trigeminal and ambigual nuclei, inferior olive and pyramids. Mild neuronal degeneration and depigmentation were observed in the substantia nigra and locus coeruleus. No abnormal protein accumulations and no demyelination or axonal degeneration were found. These neuropathological findings may provide insights into the pathophysiology of SD. PMID:19795469

Cerebral glucose metabolism in Parkinson's disease

International Nuclear Information System (INIS)

Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

1984-01-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

Genetic differentiation and spatial structure of Geosmithia morbida, the causal agent of thousand cankers disease in black walnut (Juglans nigra)

Czech Academy of Sciences Publication Activity Database

Hadziabdic, D.; Vito, L.; Windham, M. T.; Pscheidt, J. W.; Trigiano, R. N.; Kolařík, Miroslav

2014-01-01

Roč. 60, č. 2 (2014), s. 75-87 ISSN 0172-8083 Institutional support: RVO:61388971 Keywords : Thousand cankers disease * Juglans nigra * Geosmithia morbida Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.682, year: 2014

Callus induction of leaf explant Piper betle L. Var Nigra with combination of plant growth regulators indole-3-acetic acid (IAA), benzyl amino purin (BAP) and kinetin

Science.gov (United States)

Junairiah, Zuraidassanaaz, Nabilah Istighfari; Izdihar, Fairuz Nabil; Manuhara, Yosephine Sri Wulan

2017-09-01

The purpose of this research was to determine the combination of plant growth regulators IAA, BAP and kinetin towards callus induction and growth of leaf explants Piper betle L. VarNigra. Explants from leaf of Piper betle L. VarNigra was cultured on MS medium with 24 treatment combinations of plant growth regulators IAA and BAP and 24 treatment combinations of plant growth regulators IAA and kinetin with 0.0;0.5;1.0;1.5;2.0 mg/L concentration respectively, the observed variable were the length of time the formation of callus, callus morphology, fresh and dry weight of callus. The results of this research showed that the combination of growth regulators IAA with BAP and kinetin had effects on leaf growth of Piper betle L. VarNigra. During 8 weeks observation, it indicated that the combination of concentration IAA 0.5 mg/L and BAP 2.0 mg/L showed fastest callus formation at 8.5 days. Combination of concentration IAA 1.0 mg/L and BAP 1.5 mg/L showed the highest of fresh weight at 0.6596 grams, and the highest dry weight was obtained from the combination of concentration IAA 0.5 mg/L and BAP 0.5 mg/L at 0.0727 grams. Combination of concentration IAA 1.0 mg/L and kinetin 1.5 mg/L had the highest of fresh weight at 0.2972 grams and the highest dry weight at 0.1660 grams. Callus of Piper betle L. VarNigra had two textures, that were compact and friable, and also showed various kind of colors, like white, greenish white, yellowish white, tanned white, brown and black. Based on this research, that concentration IAA 1.0 mg/L and 1.5 mg/L kinetin was the best combination for induction of callus from leaf of Piper betle L. Var Nigra.

Caracterización fármaco-toxicológica de la planta medicinal Sambucus nigra subsp. canadensis (L. R. Bolli Pharmaceutical-toxicological characterization of medicinal plant Sambucus nigra subsp. canadensis (L. R. Bolli

Directory of Open Access Journals (Sweden)

Oneyda Clapé Laffita

2011-12-01

Full Text Available El objetivo de la monografía consistió en la caracterización fármaco-toxicológica de Sambucus nigra subsp. canadensis (L. R. Bolli, planta tradicional cubana con actividad antiinflamatoria, entre otras. Se presentan aspectos farmacológicos como composición fitoquímica, propiedades atribuidas popularmente y comprobadas científicamente, posología, reacciones adversas, advertencias, interacciones, toxicidad, precauciones y contraindicaciones. Se concluye que con la monografía fármaco-toxicológica de esta planta medicinal, se dispone de una completa información, como documentación indispensable para actualizar las bases de datos nacionales e internacionales al respecto, con vistas a desarrollar nuevos fitofármacos, en especial antiinflamatorios con bajo potencial de efectos adversos.The objective of the monograph was the pharmacological and toxicological characterization of Sambucus nigra subspecies canadensis(L. R. Bolli, a Cuban traditional plant with anti-inflammatory action, among others. Several pharmacological aspects such as phytochemical composition; scientifically tested properties attributed by the population; posology; adverse reactions; warnings; interactions; toxicity; precautions and counterindications were presented. It was concluded that the pharmaceutical and toxicological monograph of this plant provides full information as indispensable documentation to update national and international databases, with a view to developing new pharmaceuticals, particularly anti-inflammatory drugs with low adverse effect potential.

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

PROCESS OPTIMIZATION OF TETRA ACETYL ETHYLENE DIAMINE ACTIVATED HYDROGEN PEROXIDE BLEACHING OF POPULUS NIGRA CTMP

OpenAIRE

Qiang Zhao; Junwen Pu; Shulei Mao; Guibo Qi

2010-01-01

To enhance the bleaching efficiency, the activator of tetra acetyl ethylene diamine (TAED) was used in conventional H2O2 bleaching. The H2O2/TAED bleaching system can accelerate the reaction rate and shorten bleaching time at relative low temperature, which can reduce the production cost. In this research, the process with hydrogen peroxide activated by TAED bleaching of Populus nigra chemi-thermo mechanical pulp was optimized. Suitable bleaching conditions were confirmed as follows: pulp con...

White piedra, black piedra, tinea versicolor, and tinea nigra: contribution to the diagnosis of superficial mycosis.

Science.gov (United States)

Veasey, John Verrinder; Avila, Ricardo Bertozzi de; Miguel, Barbara Arruda Fraletti; Muramatu, Laura Hitomi

2017-01-01

Superficial mycoses are fungal infections restricted to the stratum corneum and to the hair shafts, with no penetration in the epidermis; they are: white piedra, black piedra, tinea versicolor, and tinea nigra. This study presents images of mycological tests performed in the laboratory, as well as exams performed at the authors office, in order to improve the dermatologist's knowledge about the diagnosis of these dermatoses, which are common in many countries.

The subspecific characters and distribution of the New World Skimmers - Rynchops nigra The subspecific characters and distribution of the New World Skimmers - Rynchops nigra

Directory of Open Access Journals (Sweden)

Wetmore Alexander

1944-09-01

Full Text Available The distribution of the forms of the New World rayador, or skimmer, Rynchops nigra, and the characters that mark the geographic races, have been matters of interest to me for a number of years, an interest heightened by recent discussions in current literature of the identity of the birds found on the Pacific coast of Mexico, and far to the south in Chile. Investigation into these matters with the material available in the National Museum not being conclusive, specimens from Mexico and the West Indies southward to Argentina and Chile in other large collections in the United states have been assembled through the courtesy of Dr. Robert Cushman Murphy of the American Museum of Natural History, James l.. Peters of the Museum of Comparative Zoology,W. E. C. Todd of the Carnegie Museum, and Dr. Karl P. Schmidt of the Field Museum of Natural History. I have also to thank Dr. Alden H. Miller for the use of one specimen from Chubut in the Museum of Vertebrate Zoology, and Dean Amadon for certain notes on this group of birds that he had assembled.The distribution of the forms of the New World rayador, or skimmer, Rynchops nigra, and the characters that mark the geographic races, have been matters of interest to me for a number of years, an interest heightened by recent discussions in current literature of the identity of the birds found on the Pacific coast of Mexico, and far to the south in Chile. Investigation into these matters with the material available in the National Museum not being conclusive, specimens from Mexico and the West Indies southward to Argentina and Chile in other large collections in the United states have been assembled through the courtesy of Dr. Robert Cushman Murphy of the American Museum of Natural History, James l.. Peters of the Museum of Comparative Zoology,W. E. C. Todd of the Carnegie Museum, and Dr. Karl P. Schmidt of the Field Museum of Natural History. I have also to thank Dr. Alden H. Miller for the use of one specimen

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

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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.

Assessing the direct effects of deep brain stimulation using embedded axon models

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Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

2007-06-01

To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.

Computation of an MRI brain atlas from a population of Parkinson’s disease patients

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Angelidakis, L.; Papageorgiou, I. E.; Damianou, C.; Psychogios, M. N.; Lingor, P.; von Eckardstein, K.; Hadjidemetriou, S.

2017-11-01

Parkinson’s Disease (PD) is a degenerative disorder of the brain. This study presents an MRI-based brain atlas of PD to characterize associated alterations for diagnostic and interventional purposes. The atlas standardizes primarily the implicated subcortical regions such as the globus pallidus (GP), substantia nigra (SN), subthalamic nucleus (STN), caudate nucleus (CN), thalamus (TH), putamen (PUT), and red nucleus (RN). The data were 3.0 T MRI brain images from 16 PD patients and 10 matched controls. The images used were T1-weighted (T 1 w), T2-weighted (T 2 w) images, and Susceptibility Weighted Images (SWI). The T1w images were the reference for the inter-subject non-rigid registration available from 3DSlicer. Anatomic labeling was achieved with BrainSuite and regions were refined with the level sets segmentation of ITK-Snap. The subcortical centers were analyzed for their volume and signal intensity. Comparison with an age-matched control group unravels a significant PD-related T1w signal loss in the striatum (CN and PUT) centers, but approximately a constant volume. The results in this study improve MRI based PD localization and can lead to the development of novel biomarkers.

Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

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Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

2012-11-01

Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Early life exposure to permethrin: a progressive animal model of Parkinson's disease.

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Nasuti, Cinzia; Brunori, Gloria; Eusepi, Piera; Marinelli, Lisa; Ciccocioppo, Roberto; Gabbianelli, Rosita

Oxidative stress, alpha-synuclein changes, mitochondrial complex I defects and dopamine loss, observed in the striatum of rats exposed to the pesticide permethrin in early life, could represent neuropathological hallmarks of Parkinson's disease (PD). Nevertheless, an animal model of PD should also fulfill criteria of face and predictive validities. This study was designed to: 1) verify dopaminergic status in the striatum and substantia nigra pars compacta; 2) recognize non-motor symptoms; 3) investigate the time-course development of motor disabilities; 4) assess L-Dopa effectiveness on motor symptoms in rats previously exposed to permethrin in early life. The permethrin-treated group received 34mg/kg daily of permethrin from postnatal day 6 to 21, whereas the age-matched control group was administered with the vehicle only. At adolescent age, the permethrin-treated group showed decreased levels of dopamine in the striatum, loss of dopaminergic neurons in the substantia nigra pars compacta and cognitive impairments. Motor coordination defects appeared at adult age (150days old) in permethrin-treated rats on rotarod and beam walking tasks, whereas no differences between the treated and control groups were detected on the foot print task. Predictive validity was evaluated by testing the ability of L-Dopa (5, 10 or 15mg/kg, os) to restore the postural instability in permethrin-treated rats (150days old) tested in a beam walking task. The results revealed full reversal of motor deficits starting from 10mg/kg of L-Dopa. The overall results indicate that this animal model replicates the progressive, time-dependent nature of the neurodegenerative process in Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Design and evaluation of mucoadhesive microemulsion for neuroprotective effect of ibuprofen following intranasal route in the MPTP mice model.

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Mandal, Surjyanarayan; Mandal, Snigdha Das; Chuttani, Krishna; Sawant, Krutika K; Subudhi, Bharat Bhushan

2016-08-01

The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals. Immunohistochemistry was performed. Optimal MMEI was stable and non-ciliotoxic with 66.29 ± 4.15 nm as average globule size and -20.9 ± 3.98 mV as zeta potential. PDI value and transmission electron microscopy result showed the narrow globule size distribution of MMEI. The result showed that all three independent variables had a significant effect (p open-field test findings revealed the significant improvement in motor performance and gross behavioral activity of the mice. The results from in vivo study and immunohistochemistry showed that nasal administration of Ibuprofen significantly reduced the MPTP-mediated dopamine depletion. Furthermore TH neurons count in the substantia nigra and the density of striatal dopaminergic nerve terminals were found to be significant higher for ibuprofen treated groups. Findings of the investigation revealed that Ibuprofen through developed MMEI was shown to protect neurons against MPTP-induced injury in the Substantia nigra pars compacta (SNpc) and striatum and hence, could be a promising approach for brain targeting of Ibuprofen through intranasal route to treat PD.

Indirect application of near infrared light induces neuro-protection in a mouse model of parkinsonism - an abscopal neuro-protective effective evaluation

International Nuclear Information System (INIS)

Johnstone, D.M.; Spana, S.; Purushothuman, S.; Stone, J.; Mitrofanis, J.; Johnstone, D.M.; Spana, S.; Purushothuman, S.; Stone, J.; El Massri, N.; Mitrofanis, J.; Moro, C.; Torres, N.; Chabrol, C.; De Jaeger, X.; Reinhart, F.; Benabid, A.L.; Wang, X.S.

2014-01-01

We have previously shown near infrared light (NIr), directed transcranially, mitigates the loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a model of parkinsonism. These findings complement others suggesting NIr treatment protects against damage from various insults. However one puzzling feature of NIr treatment is that unilateral exposure can lead to a bilateral healing response, suggesting NIr may have 'indirect' protective effects. We investigated whether remote NIr treatment is neuro-protective by administering different MPTP doses (50-, 75-, 100-mg/kg) to mice and treating with 670-nm light directed specifically at either the head or body. Our results show that, despite no direct irradiation of the damaged tissue, remote NIr treatment produces a significant rescue of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta at the milder MPTP dose of 50-mg/kg (30% increase vs sham-treated MPTP mice, p≤ 0.05). However this protection did not appear as robust as that achieved by direct irradiation of the head (50% increase vs sham-treated MPTP mice, p ≤0.001). There was no quantifiable protective effect of NIr at higher MPTP doses, irrespective of the delivery mode. Astrocyte and microglia cell numbers in substantia nigra pars compacta were not influenced by either mode of NIr treatment. In summary, the findings suggest that treatment of a remote tissue with NIr is sufficient to induce protection of the brain, reminiscent of the 'abscopal effect' sometimes observed in radiation treatment of metastatic cancer. This discovery has implications for the clinical translation of light-based therapies, providing an improved mode of delivery over trans-cranial irradiation. (authors)

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

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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.

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.

Multi-modal and targeted imaging improves automated mid-brain segmentation

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Plassard, Andrew J.; D'Haese, Pierre F.; Pallavaram, Srivatsan; Newton, Allen T.; Claassen, Daniel O.; Dawant, Benoit M.; Landman, Bennett A.

2017-02-01

The basal ganglia and limbic system, particularly the thalamus, putamen, internal and external globus pallidus, substantia nigra, and sub-thalamic nucleus, comprise a clinically relevant signal network for Parkinson's disease. In order to manually trace these structures, a combination of high-resolution and specialized sequences at 7T are used, but it is not feasible to scan clinical patients in those scanners. Targeted imaging sequences at 3T such as F-GATIR, and other optimized inversion recovery sequences, have been presented which enhance contrast in a select group of these structures. In this work, we show that a series of atlases generated at 7T can be used to accurately segment these structures at 3T using a combination of standard and optimized imaging sequences, though no one approach provided the best result across all structures. In the thalamus and putamen, a median Dice coefficient over 0.88 and a mean surface distance less than 1.0mm was achieved using a combination of T1 and an optimized inversion recovery imaging sequences. In the internal and external globus pallidus a Dice over 0.75 and a mean surface distance less than 1.2mm was achieved using a combination of T1 and FGATIR imaging sequences. In the substantia nigra and sub-thalamic nucleus a Dice coefficient of over 0.6 and a mean surface distance of less than 1.0mm was achieved using the optimized inversion recovery imaging sequence. On average, using T1 and optimized inversion recovery together produced significantly improved segmentation results than any individual modality (p<0.05 wilcox sign-rank test).

Age-related deposition of brain iron in normal adults: an in vivo susceptibility weighted imaging study

International Nuclear Information System (INIS)

Wang Qidong; Xu Xiaojun; Zhang Minming

2008-01-01

Objective: The purpose of this study was to investigate the effect of age on the iron concentration of the human brain. Methods: The brain iron level was evaluated in vivo in 78 healthy adult volunteers using a noninvasive magnetic resonance method termed susceptibility weighted imaging. The subjects were divided intothree groups due to different ages: young (22-35 years old, n=27), middle- aged (36-55 years old, n=35), and aged (56-78 years old, n=16). The phase values were measured on the corrected phase images in the globus pallidus, putamen, caudate, substantia nigra, red nucleus, thalamus and frontal white matter. The phase values of those regions measured from the subjects over than 30 years old were correlated with published values of brain iron concentration in normal adults to check the validity of the data. Then, the phase values of the three groups were tested for significant age-related differences using one-way ANOVA, followed by post hoc testing using least significant difference (LSD) procedure. Regression analysis was used to further examine age-related effects revealed by group comparisons, and to estimate the rates of age-related changes. Results: A strong negative correlation was found between the phase values and the published values of the brain iron concentration (r=-0.796, P= 0.032), which indicated that the higher the iron deposition level, the greater the negative phase values. In the putamen (F=20.115, P<0.01) and frontal white matter (F=3.536, P=0.034), significant differences were detected in the phase values of the three age groups. Linear regression analysis showed that phase values of the putamen, frontal white matter, and red nucleus decreased with age (The regression coefficients were -0.001, -0.001, and < -0.001 respectively, and the P value were all < 0.05), which indicated that the iron concentration of those brain structures increased with age. No significant age- related changes of the iron concentration were found in the

White piedra, black piedra, tinea versicolor, and tinea nigra: contribution to the diagnosis of superficial mycosis*

Science.gov (United States)

Veasey, John Verrinder; de Avila, Ricardo Bertozzi; Miguel, Barbara Arruda Fraletti; Muramatu, Laura Hitomi

2017-01-01

Superficial mycoses are fungal infections restricted to the stratum corneum and to the hair shafts, with no penetration in the epidermis; they are: white piedra, black piedra, tinea versicolor, and tinea nigra. This study presents images of mycological tests performed in the laboratory, as well as exams performed at the authors office, in order to improve the dermatologist's knowledge about the diagnosis of these dermatoses, which are common in many countries. PMID:29186263

Research progress of rehabilitation therapy in Parkinson's disease and its mechanism

Directory of Open Access Journals (Sweden)

Jin LIU

2017-07-01

Full Text Available Parkinson's disease (PD is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta. Rehabilitation therapy can delay the development of disease, improve motor symptoms and non - motor symptoms (NMS, and consequently improve the activities of daily living (ADL in patients with PD. The mechanism of rehabilitation improving the symptoms of PD is very complex, involving a variety of molecular mechanisms. Thus, this review will focus on the effect of rehabilitation therapy on PD and the underlying molecular mechanism including neurotransmitters, trophic factors, synaptic plasticity and immune system. DOI: 10.3969/j.issn.1672-6731.2017.06.003

CT findings in a case of Japanese encephalitis

International Nuclear Information System (INIS)

Toyomasu, Teruo; Nakashima, Kenichi; Matsumoto, Tomie; Shida, Kenshiro

1982-01-01

A 44-year-old man was admitted to a hospital on August 1980, with chief complaints of high fever and consciousness disturbance. Three months later he was referred to our hospital. Neurological examination revealed mental deterioration, amnesia, bilateral pyramidal signs, tremor, truncal ataxia and others. Serum CF titer to Japanese encephalitis virus was 1 : 16. He was diagnosed as having Japanese encephalitis from the clinical features and serological response. CT scans showed low density areas in bilateral thalami, the left ganglia, left internal capsule, left substantia nigra and others. It is noticeable that the CT findings were compatible with the pathological changes of Japanese encephalitis. (author)

Recovery of neurological functions in non-human primate model of Parkinson's disease by transplantation of encapsulated neonatal porcine choroid plexus cells.

Science.gov (United States)

Luo, Xian-Ming; Lin, Hai; Wang, Wei; Geaney, Marilyn S; Law, Lee; Wynyard, Shaun; Shaikh, Shamim B; Waldvogel, Henry; Faull, Richard L M; Elliott, Robert B; Skinner, Stephen J M; Lee, Jacqueline E; Tan, Paul L-J

2013-01-01

Parkinson's disease (PD) is a neurodegenerative disease that is primarily characterized by degeneration of dopaminergic (DA) neurons in the substantia nigra (SN) and a loss of their fibre projections in the striatum. We utilized the neonatal porcine choroid plexus (CP), an organ that secretes cerebrospinal fluid containing various types of neurotrophic and neuroprotective factors, to ameliorate the Parkinsonian symptoms in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated rhesus monkeys without requiring immunosuppression. We demonstrate that transplanted encapsulated CP clusters (eCPs) significantly improved neurological functions in MPTP-treated monkeys during the course of six months after transplantation (p Parkinson's disease.

Extracts of Morus nigra L. Leaves Standardized in Chlorogenic Acid, Rutin and Isoquercitrin: Tyrosinase Inhibition and Cytotoxicity.

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Marcela Medeiros de Freitas

Full Text Available Melanogenesis is a process responsible for melanin production, which is stored in melanocytes containing tyrosinase. Inhibition of this enzyme is a target in the cosmetics industry, since it controls undesirable skin conditions such as hyperpigmentation due to the overproduction of melanin. Species of the Morus genus are known for the beneficial uses offered in different parts of its plants, including tyrosinase inhibition. Thus, this project aimed to study the inhibitory activity of tyrosinase by extracts from Morus nigra leaves as well as the characterization of its chromatographic profile and cytotoxicity in order to become a new therapeutic option from a natural source. M. nigra leaves were collected, pulverized, equally divided into five batches and the standardized extract was obtained by passive maceration. There was no significant difference between batches for total solids content, yield and moisture content, which shows good reproducibility of the extraction process. Tyrosinase enzymatic activity was determined for each batch, providing the percentage of enzyme inhibition and IC50 values obtained by constructing dose-response curves and compared to kojic acid, a well-known tyrosinase inhibitor. High inhibition of tyrosinase activity was observed (above 90% at 15.625 μg/mL. The obtained IC50 values ranged from 5.00 μg/mL ± 0.23 to 8.49 μg/mL ± 0.59 and were compared to kojic acid (3.37 μg/mL ± 0.65. High Performance Liquid Chromatography analysis revealed the presence of chlorogenic acid, rutin and, its major compound, isoquercitrin. The chromatographic method employed was validated according to ICH guidelines and the extract was standardized using these polyphenols as markers. Cytotoxicity, assessed by MTT assay, was not observed on murine melanomas, human keratinocytes and mouse fibroblasts in tyrosinase IC50 values. This study demonstrated the potential of M. nigra leaf extract as a promising whitening agent of natural source

Tribal love: the neural correlates of passionate engagement in football fans.

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Duarte, Isabel C; Afonso, Sónia; Jorge, Helena; Cayolla, Ricardo; Ferreira, Carlos; Castelo-Branco, Miguel

2017-05-01

The tribal character of the affective link between football fans and their teams is a well-recognized phenomenon. Other forms of love such as romantic or maternal attachment have previously been studied from a neuroimaging point of view. Here we aimed to investigate the neural basis of this tribal form of love, which implies both the feeling of belongingness and rivalry against opposing teams. A pool of 56 participants was submitted to an fMRI experimental design involving the presentation of winning and losing football moments of their loved, rival or neutral teams. We found recruitment of amygdala and reward regions, including the ventral tegmental area (VTA) and substantia nigra (SN), as well as other limbic regions involved in emotional cognition, for 'positive vs neutral' and 'positive vs negative' conditions. The latter contrast was correlated with neuropsychological scores of fanaticism in the amygdala and regions within the reward system, as the VTA and SN. The observation of increased response patterns in critical components of the reward system, in particular for positive content related to the loved team, suggests that this kind of non-romantic love reflects a specific arousal and motivational state, which is biased for emotional learning of positive outcomes. © The Author (2017). Published by Oxford University Press.

Remembering with gains and losses: effects of monetary reward and punishment on successful encoding activation of source memories.

Science.gov (United States)

Shigemune, Yayoi; Tsukiura, Takashi; Kambara, Toshimune; Kawashima, Ryuta

2014-05-01

The motivation of getting rewards or avoiding punishments reinforces learning behaviors. Although the neural mechanisms underlying the effect of rewards on episodic memory have been demonstrated, there is little evidence of the effect of punishments on this memory. Our functional magnetic resonance imaging (fMRI) study investigated the effects of monetary rewards and punishments on activation during the encoding of source memories. During encoding, participants memorized words (item) and locations of presented words (source) under 3 conditions (Reward, Punishment, and Control). During retrieval, participants retrieved item and source memories of the words and were rewarded or penalized according to their performance. Source memories encoded with rewards or punishments were remembered better than those without such encoding. fMRI data demonstrated that the ventral tegmental area and substantia nigra and nucleus accumbens activations reflected both the processes of reward and punishment, whereas insular activation increased as a linear function of punishment. Activation in the hippocampus and parahippocampal cortex predicted subsequent retrieval success of source memories. Additionally, correlations between these reward/punishment-related regions and the hippocampus were significant. The successful encoding of source memories could be enhanced by punishments and rewards, and interactions between reward/punishment-related regions and memory-related regions could contribute to memory enhancement by reward and/or punishment.

Remembering with Gains and Losses: Effects of Monetary Reward and Punishment on Successful Encoding Activation of Source Memories

Science.gov (United States)

Shigemune, Yayoi; Tsukiura, Takashi; Kambara, Toshimune; Kawashima, Ryuta

2014-01-01

The motivation of getting rewards or avoiding punishments reinforces learning behaviors. Although the neural mechanisms underlying the effect of rewards on episodic memory have been demonstrated, there is little evidence of the effect of punishments on this memory. Our functional magnetic resonance imaging (fMRI) study investigated the effects of monetary rewards and punishments on activation during the encoding of source memories. During encoding, participants memorized words (item) and locations of presented words (source) under 3 conditions (Reward, Punishment, and Control). During retrieval, participants retrieved item and source memories of the words and were rewarded or penalized according to their performance. Source memories encoded with rewards or punishments were remembered better than those without such encoding. fMRI data demonstrated that the ventral tegmental area and substantia nigra and nucleus accumbens activations reflected both the processes of reward and punishment, whereas insular activation increased as a linear function of punishment. Activation in the hippocampus and parahippocampal cortex predicted subsequent retrieval success of source memories. Additionally, correlations between these reward/punishment-related regions and the hippocampus were significant. The successful encoding of source memories could be enhanced by punishments and rewards, and interactions between reward/punishment-related regions and memory-related regions could contribute to memory enhancement by reward and/or punishment. PMID:23314939

GERMINAÇÃO IN VITRO DE DALBERGIA NIGRA VELL. FR. ALL. EX BENTH

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João Otávio Silva Malaquias; Aline Tintori Mantovani; Tabatta Caroline Cerri França; Geisiele Silva Martins; Renan Carrari dos Santos; Mariana Spala Corrêa; Elias Terra Werner

2017-01-01

A história do Brasil é inteiramente ligada a espécies nativas que moveram a economia do país por décadas, entre essas espécies está o jacarandá-da-bahia (Dalbergia nigra Vell. Fr. All. Ex Benth), cuja madeira possui alto valor comercial. Sua exploração aliada à falta de manejo levou essa espécie a figurar na lista das espécies ameaçadas de extinção da flora brasileira. Diante do exposto, o objetivo do presente trabalho foi avaliar as condições mais favoráveis à germinação e estabelecimento in...

First Report of Korean Cyst Nematode, Heterodera koreana, Parasitic on Bamboo, Phyllostachys nigra, from Iran.

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Maafi, Zahra Tanha; Taheri, Zahra Majd

2015-09-01

Bamboo is grown sporadically in the north of Iran and is confined to very limited areas. The history of growing bamboo was to some extent simultaneous with the entrance, commencement, and growth of the tea industry in the north about a century ago. The bamboo was used for making baskets to transfer the harvested tea foliage from farm to the factory and other linked functions. A main area allocated for bamboo growing is located in Lahidjan Agricultural Research Station (LARS) in the north of Iran, where several species of bamboo were cultivated in an area of 5 ha. The species include five species of Phyllostachys (viz., P. aurea, P. bambusoides, P. decora, P. nigra, P. vivax) and one species of Arundinaria gigantean, Pleioblastus fortune, and Semiarundinaria fastuosa; however, only P. aurea and P. nigra have been precisely identified. A survey on plant parasitic nematodes associated with bamboo mainly on P. nigra in LARS revealed second-stage juveniles of cyst forming nematode in soil samples. Further analysis of root and soil samples led to recovery of a cyst nematode belonging to the genus Heterodera and the Afenestrata group. Cysts, vulval cone, and second-stage juveniles were studied for morphological and morphometric features. The classical identification was followed by amplification of the ribosomal RNA-ITS region and the D2-D3 expansion segments of 28S large-subunit rRNA gene; the amplified fragments were sequenced, edited, and compared with those of the corresponding published gene sequences. New D2-D3 and rRNA-ITS gene sequences were deposited in the GenBank database under the accession numbers KR818910 and KR818911, respectively. Based on the morphological and molecular data, the species of the cyst-forming nematode was identified as H. koreana (Vovlas et al., 1992; Mundo-Ocampo et al., 2008). The body contour of cysts was mainly subspherical, vey often with irregular shape (Fig. 1A), yellowish to light brown, thin cuticle with fine zigzag pattern

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

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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.

CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease

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Richard L. Jayaraj

2014-01-01

Full Text Available Copious experimental and postmortem studies have shown that oxidative stress mediated degeneration of nigrostriatal dopaminergic neurons underlies Parkinson’s disease (PD pathology. CNB-001, a novel pyrazole derivative of curcumin, has recently been reported to possess various neuroprotective properties. This study was designed to investigate the neuroprotective mechanism of CNB-001 in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP rodent model of PD. Administration of MPTP (30 mg/kg for four consecutive days exacerbated oxidative stress and motor impairment and reduced tyrosine hydroxylase (TH, dopamine transporter, and vesicular monoamine transporter 2 (VMAT2 expressions. Moreover, MPTP induced ultrastructural changes such as distorted cristae and mitochondrial enlargement in substantia nigra and striatum region. Pretreatment with CNB-001 (24 mg/kg not only ameliorated behavioral anomalies but also synergistically enhanced monoamine transporter expressions and cosseted mitochondria by virtue of its antioxidant action. These findings support the neuroprotective property of CNB-001 which may have strong therapeutic potential for treatment of PD.

Urban air pollution targets the dorsal vagal complex and dark chocolate offers neuroprotection.

Science.gov (United States)

Villarreal-Calderon, Rafael; Torres-Jardón, Ricardo; Palacios-Moreno, Juan; Osnaya, Norma; Pérez-Guillé, Beatriz; Maronpot, Robert R; Reed, William; Zhu, Hongtu; Calderón-Garcidueñas, Lilian

2010-12-01

Mexico City (MC) residents exposed to fine particulate matter and endotoxin exhibit inflammation of the olfactory bulb, substantia nigra, and vagus nerve. The goal of this study was to model these endpoints in mice and examine the neuroprotective effects of chocolate. Mice exposed to MC air received no treatment or oral dark chocolate and were compared to clean-air mice either untreated or treated intraperitoneally with endotoxin. Cyclooxygenase-2 (COX-2), interleukin 1 beta (IL-1β), and CD14 messenger RNA (mRNA) were quantified after 4, 8, and 16 months of exposure in target brain regions. After 16 months of exposure, the dorsal vagal complex (DVC) exhibited significant inflammation in endotoxin-treated and MC mice (COX-2 and IL-1β P<.001). Mexico City mice had olfactory bulb upregulation of CD14 (P=.002) and significant DVC imbalance in genes for antioxidant defenses, apoptosis, and neurodegeneration. These findings demonstrate sustained DVC inflammation in mice exposed to MC air, which is mitigated by chocolate administration. © The Author(s) 2010

Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry.

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Filbey, Francesca M; Claus, Eric; Audette, Amy R; Niculescu, Michelle; Banich, Marie T; Tanabe, Jody; Du, Yiping P; Hutchison, Kent E

2008-05-01

A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems.

Iron, dopamine, genetics, and hormones in the pathophysiology of restless legs syndrome.

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Khan, Farhan H; Ahlberg, Caitlyn D; Chow, Christopher A; Shah, Divya R; Koo, Brian B

2017-08-01

Restless legs syndrome (RLS) is a common, chronic neurologic condition, which causes a persistent urge to move the legs in the evening that interferes with sleep. Human and animal studies have been used to study the pathophysiologic state of RLS and much has been learned about the iron and dopamine systems in relation to RLS. Human neuropathologic and imaging studies have consistently shown decreased iron in different brain regions including substantia nigra and thalamus. These same areas also demonstrate a state of relative dopamine excess. While it is not known how these changes in dopamine or iron produce the symptoms of RLS, genetic and hormone studies of RLS have identified other biologic systems or genes, such as the endogenous opioid and melanocortin systems and BTBD9 and MEIS1, that may explain some of the iron or dopamine changes in relation to RLS. This manuscript will review what is known about the pathophysiology of RLS, especially as it relates to changes in iron, dopamine, genetics, and hormonal systems.

Widespread increases in malondialdehyde immunoreactivity in dopamine-rich and dopamine-poor regions of rat brain following multiple, high doses of methamphetamine.

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Kristen Ashley eHorner

2011-05-01

Full Text Available Treatment with multiple high doses of methamphetamine (METH can induce oxidative damage, including dopamine (DA-mediated reactive oxygen species (ROS formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu and substantia nigra pars compacta (SNpc. Malondialdehyde (MDA, a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg every 2h for 6h, sacrificed one week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir in the CPu, SNpc, cortex and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area (VTA and nucleus accumbens (NAc. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system.

Using Landsat satellite imagery to detect small-size forest stands of Pinus nigra Arn. and Pinus sylvestris L. affected by Scolytidae; Uso de imagenes satelite Landsat para la deteccion de rodales de Pinus nigra Arn. y Pinus sylvestris L. afectados por escolitidos

Energy Technology Data Exchange (ETDEWEB)

Blanco, E.; Bonet, J. A.; Eizaguirre, M.

2009-07-01

Medium resolution images from multispectral sensors like Landsat TM have been extensively used for decades in order to identify decline and defoliation generated by insects and other forest pests. The present work analyses the usefulness of these kinds of images to detect small-size stands of Pinus nigra Arn. and Pinus sylvestris L. affected by Scolytidae attacks. The study area was located in the Solsones region (Eastern Pyrenees), selecting 34 training zones (17 damaged small-size stands and 17 healthy small-size stands). The exploratory analysis of the images was conducted with the ERDAS IMAGINE 8.x. program.The results of the study showed significant differences between the affected and non-affected stands in 5 of the 7 spectral bands analysed. TM5 and TM7 bands were identified as those having the highest power to detect damaged stands. The digital levels obtained and the spaces of characteristics created, both showed trends to group small-size affected stands versus healthy, achieving improvements in the methodological procedure employed. (Author) 31 refs.

Distribuição espacial de compostos orgânicos de estanho em sedimentos costeiros e em Phallusia nigra da Baía de Todos os Santos e litoral norte da Bahia - Brasil Spatial distribution of organic tin compounds in coastal sediment and Phallusia nigra of the Todos os Santos Bay and northern coast of Bahia - Brazil

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Adelmo Lowe Pletsch

2010-01-01

Full Text Available Organic tin compounds were investigated in the sediment of twenty-four stations located in the Todos os Santos Bay and the north coast of Bahia - Brazil. The concentration of these organic tin was also determined in a ascidium species of Phallusia nigra. The speciation and quantification was performed by GC-MS/MS. The highest concentrations were: tributyltin (TBT 438 ng g-1, dibutyltin (DBT 207 ng g-1, monobutyltin (MBT 423 ng g-1, diphenyltin (DPT 25.8 ng g-1 and monophenyltin (MPT 55.0 ng g-1. DBT and MBT were found in Phallusia nigra, with highest concentrations of 294.1 and 148.5 ng g-1, respectively.

The effects of age on resting state functional connectivity of the basal ganglia from young to middle adulthood.

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Manza, Peter; Zhang, Sheng; Hu, Sien; Chao, Herta H; Leung, Hoi-Chung; Li, Chiang-Shan R

2015-02-15

The basal ganglia nuclei are critical for a variety of cognitive and motor functions. Much work has shown age-related structural changes of the basal ganglia. Yet less is known about how the functional interactions of these regions with the cerebral cortex and the cerebellum change throughout the lifespan. Here, we took advantage of a convenient sample and examined resting state functional magnetic resonance imaging data from 250 adults 18 to 49 years of age, focusing specifically on the caudate nucleus, pallidum, putamen, and ventral tegmental area/substantia nigra (VTA/SN). There are a few main findings to report. First, with age, caudate head connectivity increased with a large region of ventromedial prefrontal/medial orbitofrontal cortex. Second, across all subjects, pallidum and putamen showed negative connectivity with default mode network (DMN) regions such as the ventromedial prefrontal cortex and posterior cingulate cortex, in support of anti-correlation of the "task-positive" network (TPN) and DMN. This negative connectivity was reduced with age. Furthermore, pallidum, posterior putamen and VTA/SN connectivity to other TPN regions, such as somatomotor cortex, decreased with age. These results highlight a distinct effect of age on cerebral functional connectivity of the dorsal striatum and VTA/SN from young to middle adulthood and may help research investigating the etiologies or monitoring outcomes of neuropsychiatric conditions that implicate dopaminergic dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

Study of the relative toxicity of anions, with Polycelis nigra as test animal

Energy Technology Data Exchange (ETDEWEB)

Jones, J R.E.

1942-01-01

A brief review is given of existing knowledge regarding the physiological effects of anions, and literature dealing with their relative toxicity. The degree of toxicity of twenty-seven anions to Polycelis nigra (Mueller) has been assessed, by determining in each case the molar concentration the animal survives for 48 hr. at 15-18/sup 0/C. On this basis their order of increasing toxicity is as follows; commas separate ions of similar degree of toxicity: Clnigra is 0.165 cc O/sub 2//g./hr. This is not very much less than that of the trout. Polycelis is considerably the more resistant to cyanide. This is probably connected with its capability of surviving very many hours in water containing a very reduced supply of oxygen. 34 references, 6 figures, 1 table.

Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic activation of PKCδ in cell culture and animal models of Parkinson's disease

International Nuclear Information System (INIS)

Latchoumycandane, Calivarathan; Anantharam, Vellareddy; Jin, Huajun; Kanthasamy, Anumantha; Kanthasamy, Arthi

2011-01-01

The neurotoxicant 6-hydroxydopamine (6-OHDA) is used to investigate the cellular and molecular mechanisms underlying selective degeneration of dopaminergic neurons in Parkinson's disease (PD). Oxidative stress and caspase activation contribute to the 6-OHDA-induced apoptotic cell death of dopaminergic neurons. In the present study, we sought to systematically characterize the key downstream signaling molecule involved in 6-OHDA-induced dopaminergic degeneration in cell culture and animal models of PD. Treatment of mesencephalic dopaminergic neuronal N27 cells with 6-OHDA (100 μM) for 24 h significantly reduced mitochondrial activity and increased cytosolic cytochrome c, followed by sequential activation of caspase-9 and caspase-3. Co-treatment with the free radical scavenger MnTBAP (10 μM) significantly attenuated 6-OHDA-induced caspase activities. Interestingly, 6-OHDA induced proteolytic cleavage and activation of protein kinase C delta (PKCδ) was completely suppressed by treatment with a caspase-3-specific inhibitor, Z-DEVD-FMK (50 μM). Furthermore, expression of caspase-3 cleavage site-resistant mutant PKCδ D327A and kinase dead PKCδ K376R or siRNA-mediated knockdown of PKCδ protected against 6-OHDA-induced neuronal cell death, suggesting that caspase-3-dependent PKCδ promotes oxidative stress-induced dopaminergic degeneration. Suppression of PKCδ expression by siRNA also effectively protected N27 cells from 6-OHDA-induced apoptotic cell death. PKCδ cleavage was also observed in the substantia nigra of 6-OHDA-injected C57 black mice but not in control animals. Viral-mediated delivery of PKCδ D327A protein protected against 6-OHDA-induced PKCδ activation in mouse substantia nigra. Collectively, these results strongly suggest that proteolytic activation of PKCδ is a key downstream event in dopaminergic degeneration, and these results may have important translational value for development of novel treatment strategies for PD.

Macaque accessory optic system: I. Definition of the medial terminal nucleus

International Nuclear Information System (INIS)

Cooper, H.M.; Baleydier, C.; Magnin, M.

1990-01-01

The organization of the accessory optic system (AOS) has been studied in the macaque monkey following intravitreal injections of tritiated amino acids in one eye. Retinal projections to the dorsal (DTN) and the lateral (LTN) terminal nuclei are identical to those previously described in other primate species. We observed an additional group of retinorecipient cells of the AOS, located between the cerebral peduncle and the substantia nigra, which we define as the interstitial nucleus of the superior fasiculus, medial fibers. In this report, we focus our attention on the medial terminal nucleus (MTN). Although a ventral division of this nucleus (MTNv) was not observed in the macaque, the retina projects to a group of cells in the midbrain reticular formation (MRF), which we argue to be homologous to the dorsal division of the MTN (MTNd). To provide evidence in support of this homology, the retinal projection to the MTNv and MTNd was also examined in 21 additional species from 11 orders of mammals including carnivores, marsupials, lagomorphs, rodents, bats, insectivores, tree shrews, hyraxes, pholidotes, edentates, and five additional species of primates. Whereas the retina projects to both ventral and dorsal divisions in all species studied, in haplorhine primates only the projection to the MTNd is conserved. The relative topological position of the MTNd in the MRF, dorsomedial to the substantia nigra and ventrolateral to the red nucleus, remains constant throughout the mammals. The trajectory of fiber paths innervating the MTNd is also similar in all species. In addition, the MTNd has comparable afferent and efferent connections with retina, pretectum, and vestibular nuclei in all species thus far studied. These results support the unequivocal conclusion that the MTNd is an unvarying feature of the mammalian AOS

A pharmacological analysis elucidating why, in contrast to (-)-deprenyl (selegiline), alpha-tocopherol was ineffective in the DATATOP study.

Science.gov (United States)

Miklya, I; Knoll, B; Knoll, J

2003-04-25

The Parkinson Study Group who conducted the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial designed their study in the belief that the MAO inhibitor (-)-deprenyl (selegiline), the antioxidant alpha-tocopherol, and the combination of the two compounds will slow the clinical progression of the disease to the extent that MAO activity and the formation of oxygen radicals contribute to the pathogenesis of nigral degeneration. In fact, (-)-deprenyl only delayed the onset of disability associated with early, otherwise untreated Parkinson's disease, however, in contrast to the expectation of the authors, alpha-tocopherol proved to be ineffective in the DATATOP study. Enhancer substances, (-)-deprenyl, (-)-1-phenyl-2-propylaminopentane [(-)-PPAP] the (-)-deprenyl analogue free of MAO inhibitory potency, and R-(-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] the presently known most potent enhancer substance, are peculiar stimulants. They enhance the impulse propagation mediated release of the catecholamines in the brain. Due to their enhancer effect, the amount of catecholamines released from selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus) is significantly higher in rats treated with an enhancer substance than in saline treated rats. We compared the effect of (-)-deprenyl 0.025 and 0.25 mg/kg, (-)-PPAP 0.1 mg/kg, (-)-BPAP 0.0001 mg/kg, and alpha-tocopherol 25 and 50 mg/kg, in this test. The doses of (-)-deprenyl and alpha-tocopherol were selected to be in compliance with the dose given in the DATATOP study. Compared to saline treated rats, the enhancer substances significantly increased the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium and the amount of norepinephrine released from the locus coeruleus; alpha-tocopherol was ineffective. The results indicate that alpha-tocopherol was ineffective, because, unlike (-)-deprenyl it dose not enhance

125I-β-CIT imaging study of striatal dopamine transporters in mice model of parkinsonism

International Nuclear Information System (INIS)

Liu Zhenguo; Sun Wenshan; Weng Zhongfang; Chen Shengdi; Shen Minghua; Zhu Chengmo

2001-01-01

Objective: To detect the activity of striatal dopamine transporters (DAT) in lesions of different order of severity of MPTP-induced mice model of parkinsonism by autoradiography with 125 I-β-CIT and to evaluate the clinical use of the β-CIT imaging for DAT detection. Methods: With regard to the different duration (days) of MPTP treatment, the C57BL mice were randomly divided into 5 groups, that is MPTP 1, 3, 5 and 7 day groups and control group treated with normal saline instead of MPTP. Two hours after intravenous administration with 125 I-β-CIT of 148 kBq, the brain tissue sections were imaged by autoradiography. The levels of dopamine (DA) and its metabolites were measured by high performance liquid chromatography and electrochemical detection (HPLC-ECD). The tyrosine hydroxylase (TH)-positive cells and fibres in the substantia nigra and striatum of the mice were observed by means of immunohistochemical technique. Results: As compared with control group, the radioactivity ratios of striatum to cortex (ST/CX) in 4 MPTP-treated groups were significantly reduced, by 20%, 42%, 45% and 52%, respectively. The concentrations of DA in the striatum of 4 MPTP-treated groups were remarkably decreased, by 47%, 75%, 95% and 95%, respectively. The gradual loss of DA neurons and fibres in the substantia nigra and striatum in 4 MPTP-treated groups was observed under microscopy. Conclusions: The functional abnormality of DAT paralleled the changes observed in neurochemistry and neuropathology studies in the lesions of different order of injury of the MPTP-treated mice. The β-CIT scanning for the activity of DAT may be useful for diagnosing PD at earlier phase and for monitoring the progression of the disease

SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila.

Science.gov (United States)

Zanon, Alessandra; Kalvakuri, Sreehari; Rakovic, Aleksandar; Foco, Luisa; Guida, Marianna; Schwienbacher, Christine; Serafin, Alice; Rudolph, Franziska; Trilck, Michaela; Grünewald, Anne; Stanslowsky, Nancy; Wegner, Florian; Giorgio, Valentina; Lavdas, Alexandros A; Bodmer, Rolf; Pramstaller, Peter P; Klein, Christine; Hicks, Andrew A; Pichler, Irene; Seibler, Philip

2017-07-01

Mutations in the Parkin gene (PARK2) have been linked to a recessive form of Parkinson's disease (PD) characterized by the loss of dopaminergic neurons in the substantia nigra. Deficiencies of mitochondrial respiratory chain complex I activity have been observed in the substantia nigra of PD patients, and loss of Parkin results in the reduction of complex I activity shown in various cell and animal models. Using co-immunoprecipitation and proximity ligation assays on endogenous proteins, we demonstrate that Parkin interacts with mitochondrial Stomatin-like protein 2 (SLP-2), which also binds the mitochondrial lipid cardiolipin and functions in the assembly of respiratory chain proteins. SH-SY5Y cells with a stable knockdown of Parkin or SLP-2, as well as induced pluripotent stem cell-derived neurons from Parkin mutation carriers, showed decreased complex I activity and altered mitochondrial network morphology. Importantly, induced expression of SLP-2 corrected for these mitochondrial alterations caused by reduced Parkin function in these cells. In-vivo Drosophila studies showed a genetic interaction of Parkin and SLP-2, and further, tissue-specific or global overexpression of SLP-2 transgenes rescued parkin mutant phenotypes, in particular loss of dopaminergic neurons, mitochondrial network structure, reduced ATP production, and flight and motor dysfunction. The physical and genetic interaction between Parkin and SLP-2 and the compensatory potential of SLP-2 suggest a functional epistatic relationship to Parkin and a protective role of SLP-2 in neurons. This finding places further emphasis on the significance of Parkin for the maintenance of mitochondrial function in neurons and provides a novel target for therapeutic strategies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Radioenzymatic and immunhistochemical demonstration of mono-amine oxidase in different mammals with regard to degenerative disorders of the central nervous system

International Nuclear Information System (INIS)

Konradi, C.

1987-05-01

Monoamine oxidase (MAO), an enzyme of the outer mitochondrial membrane, is involved in the degradation of biogenic amines. Its role in the metabolism of neurotransmitters in the brain like catecholamines and serotonin is of special importance. Pharmacological interests in neurological and psychiatric disorders require detailed investigations, especially through the discovery of two MAO-subtypes (MAO-A and MAO-B). Thus MAO-inhibitors offer the possibility of specific medical therapies. Activity of MAO-subtypes in several animal species and different tissues including human brain was determined biochemically via a radioenzymatic method. Examination was carried out for mode of action of both subtypes and response to several substrates and inhibitors. Aim was a survey about distinctive characteristics of MAO-A and MAO-B in one species as well as to others. Furthermore investigations about neuronal and glial distribution took place by histochemical and immuncyto-chemical methods. The histochemical method, which proofs the advantage to clear off pharmacological questions was carried out in the locus coeruleus of Meriones unguiculatus. Monoclonal antibodies against both MAO-subtypes were applied in the human brainstem and compared to polyclonal antibodies against tyrosine hydroxylase (TH). The most striking outcome was a lack of MAO in the neurons of substantia nigra, although TH-antibodies gave positive results. Hence questions remain open to explain the beneficial effect MAO-B-inhibitor l-deprenyl in dopamine-neuron degenerative disorders affecting substantia nigra. In particular the results require rethinking of the roles of MAO-A and MAO-B in human brain and the mode and site of action of drugs affecting their efficacy. Furthermore biochemical MAO-models in animals and their transferability to pharmacology in humans should be applied with limitations. This work is a further development of techniques applicable for human post mortem brain analysis. 152 refs., 21 figs

Occupancy of pramipexole (Sifrol at cerebral dopamine D2/3 receptors in Parkinson's disease patients

Directory of Open Access Journals (Sweden)

Angela Deutschländer

2016-01-01

Full Text Available Whereas positron emission tomography (PET with the antagonist ligand [18F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [18F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0.7 mg p.d., and again at a later date, after withholding pramipexole 48–72 h (OFF-Sifrol; in that condition the serum pramipexole concentration had declined by 90% and prolactin levels had increased four-fold, in conjunction with a small but significant worsening of PD motor symptoms. Exploratory comparison with historical control material showed 14% higher dopamine D2/3 availability in the more-affected putamen of patients OFF medication. On-Sifrol there was significant (p ˂ 0.01 occupancy at [18F]fallypride binding sites in globus pallidus (8% thalamus (9% and substantia nigra (19%, as well as marginally significant occupancy in frontal and temporal cortex of patients. Contrary to expectation, comparison of ON- and OFF-Sifrol results did not reveal any discernible occupancy in nucleus accumbens, or elsewhere in the extended striatum; present methods should be sensitive to a 10% change in dopamine D2/3 receptor availability in striatum; the significant findings elsewhere in the basal ganglia and in cerebral cortex are consistent with a predominance of D3 receptors in those structures, especially in substantia nigra, and imply that therapeutic effects of pramipexole may be obtained at sites outside the extended striatum.

Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice.

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Leonora E Long

Full Text Available The cannabis constituent cannabidiol (CBD possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ(9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT received vehicle or CBD (1, 50 or 100 mg/kg i.p. for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT(2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg also selectively increased GABA(A receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT(2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes.

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

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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.

Role of the combination of FA and T2* parameters as a new diagnostic method in therapeutic evaluation of parkinson's disease.

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Fang, Yuan; Zheng, Tao; Liu, Lanxiang; Gao, Dawei; Shi, Qinglei; Dong, Yanchao; Du, Dan

2017-11-17

Simple diffusion delivery (SDD) has attained good effects with only tiny amounts of drugs. Fractional anisotropy (FA) and relaxation time T2* that indicate the integrity of fiber tracts and iron concentration within brain tissue were used to evaluate the therapeutic effect of SDD. To evaluate therapeutic effect of SDD in the Parkinson's disease (PD) rat model with FA and T2* parameters. Prospective case-control animal study. Thirty-two male Sprague Dawley rats (eight normal, eight PD, eight SDD, and eight subcutaneous injection rats). Single-shot spin echo echo-planar imaging and fast low-angle shot T 2 WI sequences at 3.0T. Parameters of FA and T2* on the treated side of the substantia nigra were measured to evaluate the therapeutic effect of SDD in a PD rat model. The effects of time on FA and T2* values were analyzed by repeated measurement tests. A one-way analysis of variance was conducted, followed by individual comparisons of the mean FA and T2* values at different timepoints. The FA values on the treated side of the substantia nigra in the SDD treatment group and subcutaneous injection treatment group were significantly higher at week 1 and lower at week 6 than that of the PD control group (SDD vs. PD, week 1, adjusted P = 0.012; subcutaneous vs. PD, week 1, adjusted P T2* parameter in the SDD treatment group and subcutaneous injection treatment group was significantly higher than that in the PD control group at week 6 (SDD vs. PD, adjusted P = 0.032; subcutaneous vs. PD, adjusted P T2* parameters can potentially serve as a new effective evaluation method of the therapeutic effect of SDD. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Motor Asymmetry and Substantia Nigra Volume Are Related to Spatial Delayed Response Performance in Parkinson Disease

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Foster, Erin R.; Black, Kevin J.; Antenor-Dorsey, Jo Ann V.; Perlmutter, Joel S.; Hershey, Tamara

2008-01-01

Studies suggest motor deficit asymmetry may help predict the pattern of cognitive impairment in individuals with Parkinson disease (PD). We tested this hypothesis using a highly validated and sensitive spatial memory task, spatial delayed response (SDR), and clinical and neuroimaging measures of PD asymmetry. We predicted SDR performance would be…

Development of a reliable method for determining sex for a primitive rodent, the Point Arena mountain beaver (Aplodontia rufa nigra)

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Kristine L. Pilgrim; William J. Zielinski; Fredrick V. Schlexer; Michael K. Schwartz

2012-01-01

The mountain beaver (Aplodontia rufa) is a primitive species of rodent, often considered a living fossil. The Point Arena mountain beaver (Aplodontia rufa nigra) is an endangered subspecies that occurs in a very restricted range in northern California. Efforts to recover this taxon have been limited by the lack of knowledge on their demography, particularly sex and age...

Overstory treatment and planting season affect survival of replacement tree species in emerald ash borer threatened Fraxinus nigra forests in Minnesota, USA

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Christopher E. Looney; Anthony W. D' Amato; Brian J. Palik; Robert A. Slesak

2015-01-01

Fraxinus nigra Marsh. (black ash) wetland forests in northern Minnesota, USA, are threatened by the invasive insect, emerald ash borer (Agrilus planipennis Fairmaire (EAB)). A potential management option is promoting regeneration of tree species that are not EAB hosts to maintain ecosystem functions. Using an operational-scale...

Effects of water stress on germination of Pinus nigra Arnold. seeds

International Nuclear Information System (INIS)

Topacoglu, O.; Sevik, H.; Akkuzu, E.

2016-01-01

Climate change, global warming and the deterioration of related environmental conditions cause an important problem for forest tree species. For this reason, it is necessary to determine the response of trees to these conditions. The Objective of this study was to investigate the effects of water stress on seed germination of fifteen Pinus nigra Arnold. provenances in Turkey. For this purpose, the water stresses between 0 and -8.0 bars were obtained using polyethylene glycol-6000 (PEG) solutions. Seeds were kept for 35 days at 20 ± 0.5 degree C. In this study, significant variations between the provenances were found. Ankara Uluhan ( percent 95, 08) and Isparta Tota ( percent 85, 41) provenances at -8.0 bars having the highest cumulative germination percentages were the most resistant provenances against the water stress. This study has shown that the water stress reduced the germination speed, germination percentage and germination value. (author)

The neurotoxicity of pyridinium metabolites of haloperidol

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Agnieszka Górska

2015-10-01

Full Text Available Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such as naursea, vomiting and delirium. Clinical problems occurs during and after administration of the drug are side effects, particularly extrapyrramidal symptoms (EPS. The neurotoxicity of haloperydol may be initiated by the cationic metabolites of haloperydol, HPP+, RHPP+, formed by oxidation and reduction pathways. These metabolites are transported by human organic cation transporters (hOCT to several brain structures for exapmle, in substantia nigra, striatum, caudate nucleus, hippocampus. After reaching the dopaminergic neurons inhibits mitochondrial complex I, evidence for free radical involvement, thus leading to neurodegeneration.

Linkage of cDNA expression profiles of mesencephalic dopaminergic neurons to a genome-wide in situ hybridization database

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Simon Horst H

2009-01-01

Full Text Available Abstract Midbrain dopaminergic neurons are involved in control of emotion, motivation and motor behavior. The loss of one of the subpopulations, substantia nigra pars compacta, is the pathological hallmark of one of the most prominent neurological disorders, Parkinson's disease. Several groups have looked at the molecular identity of midbrain dopaminergic neurons and have suggested the gene expression profile of these neurons. Here, after determining the efficiency of each screen, we provide a linked database of the genes, expressed in this neuronal population, by combining and comparing the results of six previous studies and verification of expression of each gene in dopaminergic neurons, using the collection of in situ hybridization in the Allen Brain Atlas.

Transcranial Ultrasound in the Diagnosis of Parkinson’s Disease

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Aniley Martínez González

2014-10-01

Full Text Available Parkinson’s disease is the second most common neurodegenerative disorder and, since it is associated with aging, the probability of developing this disease increases with age. The diagnosis of idiopathic Parkinson’s disease is based on clinical criteria; however, its differentiation from other forms of Parkinsonism can be difficult, especially in early stages of the disease. Transcranial ultrasound has become a tool for the diagnosis of this disorder, being very useful for its early diagnosis. Ultrasonographic findings characteristic of this disease include increased echogenicity of the substantia nigra in the midbrain measured through the temporal bone window. This paper discusses the usefulness of transcranial ultrasound for early diagnosis of patients with Parkinson's disease.

Multiple sclerosis exceptionally presenting as parkinsonism responds to intravenous methylprednisolone.

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Saidha, S

2012-01-31

Parkinsonism due to multiple sclerosis (MS) is rare. In previously reported patients with MS-induced parkinsonism, MS manifested first, followed a typical clinical course, and parkinsonism developed later in the course of the illness. We report a 52-year-old male presenting with parkinsonism as the initial manifestation of MS, in whom a subsequent MS relapse consisted of marked deterioration in parkinsonism, a clinical pattern not previously described in MS. A brain MRI demonstrated involvement of the substantia nigra and basal ganglia. This patient illustrates that the clinical presentation and progression of MS may rarely be characterised by predominating parkinsonian features which are reversible by treatment with intravenous methylprednisolone and interferon beta1a.

Multiple sclerosis exceptionally presenting as parkinsonism responds to intravenous methylprednisolone.

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Saidha, S

2010-05-01

Parkinsonism due to multiple sclerosis (MS) is rare. In previously reported patients with MS-induced parkinsonism, MS manifested first, followed a typical clinical course, and parkinsonism developed later in the course of the illness. We report a 52-year-old male presenting with parkinsonism as the initial manifestation of MS, in whom a subsequent MS relapse consisted of marked deterioration in parkinsonism, a clinical pattern not previously described in MS. A brain MRI demonstrated involvement of the substantia nigra and basal ganglia. This patient illustrates that the clinical presentation and progression of MS may rarely be characterised by predominating parkinsonian features which are reversible by treatment with intravenous methylprednisolone and interferon beta1a.

Multifocal dystonia, Clinical feature of Hallervorden-Spatz

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Ghelichkhani H

1998-09-01

Full Text Available Hallervorden-spatz disease is an inherited metabolic disorder with autosomal recessive trait. Onset is in late childhood or early adolescence. Clinical manifestation is variable but pyramidal and extrapyramidal signs are often prominent. Many of patients show progressive dementia and extrapyramidal symptoms. Ataxia or myoclonus is reported in the course of the disease in individual cases. Focal dystonias including tongue, eyelids (blepharospasm and optic atrophy, retinitis pigmentosa, rarely familial parkinsonism are also reported. Pathologically pigmentary degeneration of globus pallidus, substantia nigra (pars reticular and red nucleus is characteristic. In our case the main clinical feature was multifocal dystonia without obvious pyramidal or other extrapyramidal symptoms, and diagnosis was based on clinical and MRI findings.

Effect of ZnO nanoparticles on Brassica nigra seedlings and stem explants: growth dynamics and antioxidative response

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Hira eZafar

2016-04-01

Full Text Available Nanoparticles (NPs have diverse properties in comparison to respective chemicals due to structure, surface area ratio, morphology, and reactivity. Toxicological effects of metallic NPs to organisms including plants have been reported. However, to the authors’ knowledge there is no report on the effect of NPs on in vitro culture of plant explants. In this study, ZnO NPs at 500-1500 mg/L badly affected Brassica nigra seed germination and seedling growth and raised antioxidative activities and antioxidants concentrations. On the other hand, culturing the stem explants of B. nigra on Murashige and Skoog (MS medium in presence of low concentration of ZnO NPs (1-20 mg/L produced white thin roots with thick root hairs. At 10 mg/L ZnO NPs shoots emergence was also observed. The developed calli/roots showed 79% DPPH (2,2-diphenyl-1-picryl hydrazyl radical scavenging activity at 10 mg/L. While total antioxidant and reducing power potential were also significantly different in presence of ZnO NPs. Non enzymatic antioxidative molecules, phenolics (up to 0.15 µg GAE/mg FW and flavonoids (up to 0.22 µg QE/mg FW, also raised and found NPs concentration dependent. We state that ZnO NPs may induce roots from explants cultured on appropriate medium and can be cultured for production of valuable secondary metabolites.

How specialized volatiles respond to chronic and short-term physiological and shock heat stress in Brassica nigra.

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Kask, Kaia; Kännaste, Astrid; Talts, Eero; Copolovici, Lucian; Niinemets, Ülo

2016-09-01

Brassicales release volatile glucosinolate breakdown products upon tissue mechanical damage, but it is unclear how the release of glucosinolate volatiles responds to abiotic stresses such as heat stress. We used three different heat treatments, simulating different dynamic temperature conditions in the field to gain insight into stress-dependent changes in volatile blends and photosynthetic characteristics in the annual herb Brassica nigra (L.) Koch. Heat stress was applied by either heating leaves through temperature response curve measurements from 20 to 40 °C (mild stress), exposing plants for 4 h to temperatures 25-44 °C (long-term stress) or shock-heating leaves to 45-50 °C. Photosynthetic reduction through temperature response curves was associated with decreased stomatal conductance, while the reduction due to long-term stress and collapse of photosynthetic activity after heat shock stress were associated with non-stomatal processes. Mild stress decreased constitutive monoterpene emissions, while long-term stress and shock stress resulted in emissions of the lipoxygenase pathway and glucosinolate volatiles. Glucosinolate volatile release was more strongly elicited by long-term stress and lipoxygenase product released by heat shock. These results demonstrate that glucosinolate volatiles constitute a major part of emission blend in heat-stressed B. nigra plants, especially upon chronic stress that leads to induction responses. © 2016 John Wiley & Sons Ltd.

Evaluation of anti-inflammatory activity of prenylated substances isolated from Morus alba and Morus nigra.

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Zelová, Hana; Hanáková, Zuzana; Čermáková, Zuzana; Šmejkal, Karel; Dalĺ Acqua, Stefano; Babula, Petr; Cvačka, Josef; Hošek, Jan

2014-06-27

Chromatographic separation of root extracts of Morus alba and M. nigra led to the identification of the 2-arylbenzofurans moracin C (1), mulberrofuran Y (2), and mulberrofuran H (3), and the prenylated flavonoids kuwanon E (4), kuwanon C (5), sanggenon H (6), cudraflavone B (7), and morusinol (8), and the Diels-Alder adducts soroceal (9), and sanggenon E (10). The cytotoxicity and their antiphlogistic activity, determined as the attenuation of the secretion of TNF-α and IL-1β and the inhibition of NF-κB nuclear translocation in LPS-stimulated macrophages, were evaluated for compounds 1-10.

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

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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.

Large-Scale Regeneration Patterns of Pinus nigra Subsp. salzmannii: Poor Evidence of Increasing Facilitation Across a Drought Gradient

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Pedro Antonio Tíscar

2013-12-01

Full Text Available Tree recruitment is a key process underlying stand dynamics and sustainability in managed forests. Woody plant cover is known to affect the regeneration success of Pinus nigra, suggesting the existence of facilitative plant-plant interactions. The regeneration patterns of this Mediterranean pine were analyzed across its distribution area, using data from 3226 plots of the Spanish National Forest Inventory. We aimed to test the hypothesis that seedlings establishment occurs under higher values of either canopy or shrub cover in the driest populations, as predicted by the stress-gradient hypothesis. Data were analyzed by means of Generalized Linear Models and multivariate methods. Results revealed that regeneration failure occurs on a regional scale, and that regeneration is facilitated by tree canopy cover of 55%–80%. A non-linear pattern of interaction along an aridity gradient was identified, with competition at the wettest site, high facilitation at the mid-dry sites, and low facilitation at the driest site. Evidence suggests that some shrub species may facilitate recruitment in the harsher areas. Collectively, our results reduce the possibilities of adapting forest management to drying climates by the application of alternative silvicultural prescriptions involving canopy cover.

Effective population size estimation in seed orchards: A case study of Pinus nigra ARNOLD and Fraxinus excelsior L./ F. angustifolia VAHL.

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Machanská Eva

2013-01-01

Full Text Available Effective population size as a parameter closely correlating with the genetic and genotypic diversity of the seed orchard output is an important indicator of seed orchard functioning. It is determined by the variation of male and female gametic contributions of parental genotypes (including those outside the seed orchard, influenced by the variation in male and female gamete production, reproductive phenology, pollen dispersal within seed orchard and other factors. We assessed male and female fecundity, as well as temporal course of male and female flowering in two seed orchards of Pinus nigra ARNOLD and Fraxinus excelsior L./F. angustifolia VAHL. in Slovakia. In both cases, male and female gametic contributions of plus-tree clones were modeled on the basis of fecundity and flowering phenology, and were used to calculate status number as an estimator of effective population size. In the seed orchard of Pinus nigra, marker-aided verification of clonal fidelity revealed unexpectedly high proportion of misplaced ramets (29.9% and alien genotypes (44.4%. Monitoring of reproductive processes in 2002 and 2003 showed high variation in both male and female fecundity, and pollen shedding preceding female receptivity in Pinus nigra. All these factors contributed to a very low relative status effective number, representing 8.6% to 38.6% of the population census (depending from the management option in relation to misplaced and alien genotypes. In the mixed seed orchard of Fraxinus excelsior and F. angustifolia, the proportion of misplaced and alien genotypes was much lower (22.4% and 12.3%, respectively. However, a high fecundity variation and protogyny resulted in a low relative status number (18.8% to 29.5% of the census number of clones also in this seed orchard. Practical implications of these findings are shortly discussed and practical management options are proposed.

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)

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)

Gender Differences in Verbal and Visuospatial Working Memory Performance and Networks.

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Zilles, David; Lewandowski, Mirjana; Vieker, Henning; Henseler, Ilona; Diekhof, Esther; Melcher, Tobias; Keil, Maria; Gruber, Oliver

2016-01-01

Working memory (WM) has been a matter of intensive basic and clinical research for some decades now. The investigation of WM function and dysfunction may facilitate the understanding of both physiological and pathological processes in the human brain. Though WM paradigms are widely used in neuroscientific and psychiatric research, conclusive knowledge about potential moderating variables such as gender is still missing. We used functional magnetic resonance imaging to investigate the effects of gender on verbal and visuospatial WM maintenance tasks in a large and homogeneous sample of young healthy subjects. We found significant gender effects on both the behavioral and neurofunctional level. Females exhibited disadvantages with a small effect size in both WM domains accompanied by stronger activations in a set of brain regions (including bilateral substantia nigra/ventral tegmental area and right Broca's area) independent of WM modality. As load and task difficulty effects have been shown for some of these regions, the stronger activations may reflect a slightly lower capacity of both WM domains in females. Males showed stronger bilateral intraparietal activations next to the precuneus which were specific for the visuospatial WM task. Activity in this specific region may be associated with visuospatial short-term memory capacity. These findings provide evidence for a slightly lower capacity in both WM modalities in females. © 2016 S. Karger AG, Basel.

Laboratory-scale measurements of N2O and CH4 emissions from hybrid poplars (Populus deltoides x Populus nigra).

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McBain, M C; Warland, J S; McBride, R A; Wagner-Riddle, C

2004-12-01

The purpose of this study was to determine whether or not young hybrid poplar (Populus deltoides x Populus nigra) could transport landfill biogas internally from the root zone to the atmosphere, thereby acting as conduits for landfill gas release. Fluxes of methane (CH4) and nitrous oxide (N2O) from the seedlings to the atmosphere were measured under controlled conditions using dynamic flux chambers and a tunable diode laser trace gas analyser (TDLTGA). Nitrous oxide was emitted from the seedlings, but only when extremely high soil N2O concentrations were applied to the root zone. In contrast, no detectable emissions of CH4 were measured in a similar experimental trial. Visible plant morphological responses, characteristic of flood-tolerant trees attempting to cope with the negative effects of soil hypoxia, were observed during the CH4 experiments. Leaf chlorosis, leaf abscission and adventitious roots were all visible plant responses. In addition, seedling survival was observed to be highest in the biogas 'hot spot' areas of a local municipal solid waste landfill involved in this study. Based on the available literature, these observations suggest that CH4 can be transported internally by Populus deltoides x Populus nigra seedlings in trace amounts, although future research is required to fully test this hypothesis.

RAPD markers and black pine (Pinus nigra Arnold intraspecies taxonomy - Evidence from the study of nine populations

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Zlatko Liber

2011-01-01

Full Text Available Although intraspecies researches within the black pine (Pinus nigra Arnold have a long tradition, the intraspecies taxonomy, classification and chorology are still unclear. Among the numerous reasons that have caused this situation the most important are: the absence of a study that would completely cover the whole range of this species, the impossibility of connection of results of the existing detailed studies of certain areas, and the high variability of traits which have been used so far. Since the characteristics of the molecular systematic techniques could make possible the research free of the mentioned shortages, the intention of this study was to determine the relationships among nine populations of black pine using the random amplified polymorphic DNA (RAPD. The obtained results were compared to the recent results of the morphological and anatomical analysis of the leaves of the same populations. The RAPD results clearly divided the Croatian populations from populations of Austria (subsp. nigra and Turkey (subsp. pallasiana, while among Croatian populations, as in previous study, the existence of several groups (subsp. illyrica, subsp. dalmatica and transitional population between them was noticed. It is assumed that the optimisations conducted in this study will finally make possible estimating the relationships on the level of the whole range of the black pine and the classification based on molecular traits that are probably less dependent on environmental influences than it has been the case with the characteristics mostly used so far.

Rhabdomyosarcoma in a terrestrial tortoise (Geochelone nigra in Nigeria: A case report

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Oghenemega D. Eyarefe

2012-11-01

Full Text Available A skeletal muscle tumour (rhabdomysarcoma was diagnosed in a 4-year-old captive female terrestrial tortoise (Geochelone nigra weighing 7 kg presented at the Veterinary Teaching Hospital, University of Ibadan, Ibadan, Nigeria. The tumour was located at the anterior right portion of the body and ventral to the carapace. The location of the tumour prevented the tortoise from extending its head from the body. The tumour was a sessile, smooth white mass, with a soft myxomatous consistency. The histological features that were diagnostic of rhabdomyosarcoma included a sparse population of haphazardly arranged spindle-shaped cells within a homogenous matrix (anisocytosis, occasional tumour giant and binucleate cells, and some well differentiated myofibrils with cross striations within the cytoplasm. The paucity of information on tumours in the land tortoise was the reason for this report, which appears to be the first report of rhabdomyosarcoma in the tortoise.

Diffusion tensor imaging of nigral degeneration in Parkinson's disease: A region-of-interest and voxel-based study at 3 T and systematic review with meta-analysis☆

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Schwarz, Stefan T.; Abaei, Maryam; Gontu, Vamsi; Morgan, Paul S.; Bajaj, Nin; Auer, Dorothee P.

2013-01-01

There is increasing interest in developing a reliable, affordable and accessible disease biomarker of Parkinson's disease (PD) to facilitate disease modifying PD-trials. Imaging biomarkers using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) can describe parameters such as fractional anisotropy (FA), mean diffusivity (MD) or apparent diffusion coefficient (ADC). These parameters, when measured in the substantia nigra (SN), have not only shown promising but also varying and controversial results. To clarify the potential diagnostic value of nigral DTI in PD and its dependency on selection of region-of-interest, we undertook a high resolution DTI study at 3 T. 59 subjects (32 PD patients, 27 age and sex matched healthy controls) were analysed using manual outlining of SN and substructures, and voxel-based analysis (VBA). We also performed a systematic literature review and meta-analysis to estimate the effect size (DES) of disease related nigral DTI changes. We found a regional increase in nigral mean diffusivity in PD (mean ± SD, PD 0.80 ± 0.10 vs. controls 0.73 ± 0.06 · 10− 3 mm2/s, p = 0.002), but no difference using a voxel based approach. No significant disease effect was seen using meta-analysis of nigral MD changes (10 studies, DES = + 0.26, p = 0.17, I2 = 30%). None of the nigral regional or voxel based analyses of this study showed altered fractional anisotropy. Meta-analysis of 11 studies on nigral FA changes revealed a significant PD induced FA decrease. There was, however, a very large variation in results (I2 = 86%) comparing all studies. After exclusion of five studies with unusual high values of nigral FA in the control group, an acceptable heterogeneity was reached, but there was non-significant disease effect (DES = − 0.5, p = 0.22, I2 = 28%). The small PD related nigral MD changes in conjunction with the negative findings on VBA and meta-analysis limit the usefulness of nigral MD measures as

The alterations of cortical volume, thickness, surface and density in the intermediate sporadic Parkinson's disease from the Han population of Mainland China

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Xia Deng

2016-08-01

Full Text Available Many symptoms of sporadic Parkinson's disease (sPD can’t be completely explained by the lesion of simple typical extrapyramidal circuit between striatum and substantia nigra. Therefore, we investigated the alteration of cortical volume, thickness, surface and density in the intermediate sPD from the Han population of Mainland China in order to find the new pathological brain regions associated with the complex clinical manifestations of sPD. The cortical volume, thickness, surface and density were examined using the voxel-based cortical morphometry and corticometry on magnetic resonance image (MRI in 67 intermediate sPD and 35 controls, the multiple adjusted comparisons analysis of all MRI data were employed to assess the relationships between the cortical morphometric alteration in the specific brain regions and sPD. Results showed that a significantly shrunk volume, thinned thickness and enlarged or reduced surface of cortex in some specific brain regions were closely associated with sPD, but all cortical densities were not different. The majority of morphometric alteration of hemisphere cortex was symmetric, but that in the left hemisphere was more significant. The cortical morphometric alterations in the frontal, temporal, parietal, occipital and limbic lobe, cerebellum, caudate and thalamus were closely related to the clinical neural dysfunction (Clinical manifestations of sPD. Our data indicated that the deficits of extensive brain regions involved in the development of sPD, resulted in a series of correspondent complex clinical manifestations in the disease.

GABA and benzodiazepine receptors in the gerbil brain after transient ischemia: demonstration by quantitative receptor autoradiography

International Nuclear Information System (INIS)

Onodera, H.; Sato, G.; Kogure, K.

1987-01-01

Quantitative receptor autoradiography was used to measure the binding of gamma-aminobutyric acid (GABA) and benzodiazepine receptors after ischemia by means of transient occlusion of bilateral common carotid arteries in the gerbil. [ 3 H]Muscimol was used to label the GABAA receptors and [ 3 H]flunitrazepam to label central type benzodiazepine receptors. In the superolateral convexities of the frontal cortices, [ 3 H]muscimol binding was increased in 60% of the animals killed 3 days after ischemia, and decreased in 67% of the animals killed 27 days after ischemia. Twenty-seven days after ischemia, [ 3 H]flunitrazepam binding in the substantia nigra pars reticulata increased to 252% of the control, though the increase in [ 3 H]muscimol binding was not significant. In the dorsolateral region of the caudate putamen, marked neuronal necrosis and depletion of both [ 3 H]muscimol and [ 3 H]flunitrazepam binding sites were observed 27 days after ischemia, the ventromedial region being left intact. In spite of the depletion of pyramidal cells in the CA1 region of the hippocampus, both [ 3 H]muscimol and [ 3 H]flunitrazepam binding sites were preserved 27 days after ischemia. Since our previous study revealed that adenosine A1 binding sites were depleted in the CA1 subfield of the hippocampus after ischemia correlating with neuronal damage, GABAA and benzodiazepine receptors may not be distributed predominantly on the pyramidal cells in the CA1 region

Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

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Taysa Bervian Bassani

2015-07-01

Full Text Available Parkinson’s disease (PD is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.

Attenuated neural response to gamble outcomes in drug-naive patients with Parkinson’s disease

DEFF Research Database (Denmark)

van der Vegt, Joyce P M; Hulme, Oliver J; Zittel, Simone

2013-01-01

healthy age-matched control subjects underwent whole-brain functional magnetic resonance imaging while they performed a simple two-choice gambling task resulting in stochastic and parametrically variable monetary gains and losses. In patients with Parkinson's disease, the neural response to reward outcome......Parkinson's disease results from the degeneration of dopaminergic neurons in the substantia nigra, manifesting as a spectrum of motor, cognitive and affective deficits. Parkinson's disease also affects reward processing, but disease-related deficits in reinforcement learning are thought to emerge...... at a slower pace than motor symptoms as the degeneration progresses from dorsal to ventral striatum. Dysfunctions in reward processing are difficult to study in Parkinson's disease as most patients have been treated with dopaminergic drugs, which sensitize reward responses in the ventral striatum, commonly...

Dose-dependent striatal changes in dopaminergic terminals and alpha-synuclein reactivity in a porcine model of progressive Parkinson’s disease

DEFF Research Database (Denmark)

Nielsen, Mette Slot; Glud, Andreas Nørgaard; Møller, Arne

2011-01-01

to discover effective compounds halting PD progression have so far failed in clinical trials, perhaps because current animal models do not imitate the neuropathological progression of PD well enough. We recently established a progressive large animal PD model in Göttingen minipigs based on chronic infusion......Parkinson disease (PD) is a common neurodegenerative disorder, resulting from a progressive dopaminergic neuron loss in the substantia nigra (SN). Alpha-synuclein positive neuronal inclusion bodies and progressive loss of dopaminergic striatal terminals is also well described in PD. Attempts...... the SN were paraffin embedded and immunohistochemically stained for tyrosine hydroxylase (TH) and alpha-synuclein. Stereological examination of the SN showed progressive nigral neuron loss with increased MPTP dosages. Occasional neuronal staining confined to the cytoplasm and cell membrane was observed...

Synthesis and preliminary biological evaluation of [{sup 123}I]Me{sub 2}Pyr, a new potential ligand for imaging of central cannabinoid CB{sub 1} receptors

Energy Technology Data Exchange (ETDEWEB)

Gielow, P. [Department of Nuclear Medicine, University School of Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany)]. E-mail: gielow.peter@mh-hannover.de; Klinge, P. [International Neuroscience Institute, Alexis Carrel Str. 4, D-30625 Hannover (Germany); Knapp, W.H. [Department of Nuclear Medicine, University School of Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany); Berding, G. [Department of Nuclear Medicine, University School of Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany)

2006-07-15

A synthesis of 1-(2,4-dichlorophenyl)-5-(4-[{sup 123}I]iodophenyl)-4-methyl-1H-pyrazole -3-carboxylic acid N',N'-dimethyl-hydrazide ([{sup 123}I]Me{sub 2}Pyr), a new radioiodinated analogue of the high-affinity cannabinoid CB{sub 1} receptor antagonist SR141716A, is described. Labelling was achieved by radioiododestannylation of the tributylstannyl precursor with [{sup 123}I]iodide in the presence of chloramine T. HPLC purification afforded the labelled product in 48% radiochemical yield. Preliminary rat brain biodistribution studies with the {sup 125}I labelled compound revealed high uptake in the substantia nigra, the globus pallidus externus and the cerebellum, which is consistent with the known distribution of CB{sub 1} receptors.

Magnetic resonance imaging of dystonic states

International Nuclear Information System (INIS)

Rutledge, J.N.; Hilal, S.K.; Silver, A.J.; Defendini, R.; Fahn, S.

1988-01-01

Interest in movement disorders is heightened by the recent capability of mapping the distribution of macromolecular complexes of Fe(III) in the brain using heavily T2-weighted images. This is accomplished through contrast caused by their T2 effect, a local inhomogeneity in the magnetic field which dephases spin and results in loss of signal. It is a unique characteristic of the extra-pyramidal system that its nuclei contain high concentrations of iron. The areas especially rich are the substantia nigra and globus pallidus. Lesser amounts of iron are found in the red nucleus, dentate nucleus, nigrostriatal tract, putamen, and caudate nucleus. The reasons for increased concentration of iron in nuclei related to movement are incompletely understood and are reviewed in this chapter

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....

Gamma radiation effect on Populus nigra assimilatory pigments

International Nuclear Information System (INIS)

Creanga, I. A.; Tudorie, Marcela; Mocanasu, C.; Creanga, Dorina

2002-01-01

The influence of low intensity gamma radiation on the photosynthesis in young poplar saplings was studied. Black poplar (Populus nigra) was chosen due to its ecological importance, as fast growing tree species with many hybrids, in the frame of a polluted environment. Assimilatory pigments in the leaves of irradiated saplings were assayed using standard spectrophotometric method in acetone extract. Series of five saplings formed the experimental samples. Chlorophyll a and chlorophyll b levels appeared as diminished in exposed samples in comparison to the controls. Linear regression was established in every case, the line slope showing the higher effect in chlorophyll b. Carotene pigments presented a slight increasing tendency in the exposed samples. Assimilatory pigment sum was shown to be affected by the same decreasing tendency. Student t-test was applied (two tailed, pair type) to reveal statistical significance of observed modifications. Though not very deep, the modifications induced by exposure to gamma radiation of low intensity (comparable to the local atmospheric variations, caused by both natural and artificial sources) represent putative inhibitory factors in young plant photosynthesis. The main mechanism of radiation action seems to be water radiolysis, triggering peroxide cascade, generally producing toxic products for the cell metabolism. Nevertheless, living cell ability to repair some damages caused by external stress could be revealed in the present case by the enhancing tendency of the carotenes which sustain photosynthesis as secondary pigments. (authors)

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 formation in organotypic cultures.

Antimalarial activity of 80 % methanolic extract of Brassica nigra (L.) Koch. (Brassicaceae) seeds against Plasmodium berghei infection in mice.

Science.gov (United States)

Muluye, Abrham Belachew; Melese, Eshetie; Adinew, Getnet Mequanint

2015-10-15

Resistances to currently available drugs and insecticides, significant drug toxicities and costs and lack of vaccines currently complicated the treatment of malaria. A continued search for safe, effective and affordable plant-based antimalarial agents thus becomes crucial and vital in the face of these difficulties. The aim of the study was to evaluate the antimalarial activity of 80 % methanolic extract of the seeds of Brassica nigra against Plasmodium berghei infection in mice. Chloroquine sensitive Plasmodium berghei (ANKA strain) was used to test the antimalarial activity of the extract. In suppressive and prophylactic models, Swiss albino male mice were randomly grouped into five groups of five mice each. Group I mice were treated with the vehicle, group II, III and IV were treated with 100, 200, and 400 mg/kg of the extract, respectively and the last group (V) mice were treated with chloroquine (10 mg/kg). The level of parasitemia, survival time and variation in weight of mice were used to determine the antimalarial activity of the extract. Chemosuppressive activities produced by the extract of the seeds of Brassica nigra were 21.88, 50.00 (P activities were 17.42, 21.21 and 53.79 % (P activities and the plant may contain biologically active principles which are relevant in the treatment and prophylaxis of malaria, thus supporting further studies of the plant for its active components.

Black Ash (Fraxinus nigra Marsh.): Local ecological knowledge of site characteristics and morphology associated with basket-grade specimens in New England (USA)

Science.gov (United States)

Allaire K. Diamond; Marla R. Emery

2011-01-01

Fraxinus nigra Marsh. is a small, relatively uncommon tree with large social significance. Known as black ash or brown ash, it rarely exceeds 18 meters (60 feet) in height or 30-50 centimeters (12-20 inches) in diameter. In the U.S. states where the species occurs, its percentage of forest composition ranges from 0.01% in Kentucky to 6.00% in...

Simultaneous T1 and T2 Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting.

Science.gov (United States)

Badve, Chaitra; Yu, Alice; Rogers, Matthew; Ma, Dan; Liu, Yiying; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Gulani, Vikas

2015-12-01

Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T 1 and T 2 maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T 1 and T 2 in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T 1 and T 2 of temporal regions, cerebellum and pons. Males were also found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored.

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.