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Sample records for adult rat dentate

  1. Effects of NOS inhibitor on dentate gyrus neurogenesis after diffuse brain injury in the adult rats

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    SunLi-Sha; XuJiang-ping

    2004-01-01

    Objective To investigate the effects of selective nitric oxide synthase (NOS) inhibitors on dentate gyrus neurogenesis after diffuse brain injury (DBI) in the adult rat brain. Methods Adult male SD rats were subjected to diffuse brain injury (DBI) model. By using systemic bromodeoxyuridine (BrdU) to label dividing cells, we compared the proliferation rate of

  2. Desvenlafaxine may accelerate neuronal maturation in the dentate gyri of adult male rats.

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    Aditya Asokan

    Full Text Available Adult hippocampal neurogenesis has been linked to the effects of anti-depressant drugs on behavior in rodent models of depression. To explore this link further, we tested whether the serotonin-norepinephrine reuptake inhibitor (SNRI venlafaxine impacted adult hippocampal neurogenesis differently than its primary active SNRI metabolite desvenlafaxine. Adult male Long Evans rats (n = 5-6 per group were fed vehicle, venlafaxine (0.5 or 5 mg or desvenlafaxine (0.5 or 5 mg twice daily for 16 days. Beginning the third day of drug treatment, the rats were given a daily bromodeoxyuridine (BrdU; 50 mg/kg injection for 5 days to label dividing cells and then perfused 2 weeks after the first BrdU injection to confirm total new hippocampal cell numbers and their phenotypes. The high desvenlafaxine dose increased total new BrdU+ cell number and appeared to accelerate neuronal maturation because fewer BrdU+ cells expressed maturing neuronal phenotypes and more expressed mature neuronal phenotypes in the dentate gyri of these versus vehicle-treated rats. While net neurogenesis was not increased in the dentate gyri of rats treated with the high desvenlafaxine dose, significantly more mature neurons were detected. Our data expand the body of literature showing that antidepressants impact adult neurogenesis by stimulating NPC proliferation and perhaps the survival of neuronal progeny and by showing that a high dose of the SNRI antidepressant desvenlafaxine, but neither a high nor low venlafaxine dose, may also accelerate neuronal maturation in the adult rat hippocampus. These data support the hypothesis that hippocampal neurogenesis may indeed serve as a biomarker of depression and the effects of antidepressant treatment, and may be informative for developing novel fast-acting antidepressant strategies.

  3. Novel control by the CA3 region of the hippocampus on neurogenesis in the dentate gyrus of the adult rat.

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    Jian Xin Liu

    Full Text Available The dentate gyrus is a site of continued neurogenesis in the adult brain. The CA3 region of the hippocampus is the major projection area from the dentate gyrus. CA3 sends reciprocal projections back to the dentate gyrus. Does this imply that CA3 exerts some control over neurogenesis? We studied the effects of lesions of CA3 on neurogenesis in the dentate gyrus, and on the ability of fluoxetine to stimulate mitotic activity in the progenitor cells. Unilateral ibotenic-acid generated lesions were made in CA3. Four days later there was no change on the number of either BrdU or Ki67-positive progenitor cells in the dentate gyrus. However, after 15 or 28 days, there was a marked reduction in surviving BrdU-labelled cells on the lesioned side (but no change in Ki-67+ cells. pCREB or Wnt3a did not co-localise with Ki-67 but with NeuN, a marker of mature neurons. Lesions had no effect on the basal expression of either pCREB or Wnt3a. Subcutaneous fluoxetine (10 mg/kg/day for 14 days increased the number of Ki67+ cells as expected on the control (non-lesioned side but not on that with a CA3 lesion. Nevertheless, the expected increase in BDNF, pCREB and Wnt3a still occurred on the lesioned side following fluoxetine treatment. Fluoxetine has been reported to decrease the number of "mature" calbindin-positive cells in the dentate gyrus; we found this still occurred on the side of a CA3 lesion. We then showed that the expression GAP-43 was reduced in the dentate gyrus on the lesioned side, confirming the existence of a synaptic connection between CA3 and the dentate gyrus. These results show that CA3 has a hitherto unsuspected role in regulating neurogenesis in the dentate gyrus of the adult rat.

  4. Effects of Scutellaria baicalensis on neurogenesis in the hippocampal dentate gyrus and on spatial memory of adult rats

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    Sun-Hwa Lee; Byung-II Min; Byung-soo Ahn; Bong-soo Lim; Seong-Kyu Kim; Sam-Ki Kim; Dae-II Lee; Sung-Rae Cho; Deok-Gon Kim; Jae-Bok Han

    2011-01-01

    We investigated the effects of ethanol extracted Scutellaria baicalensis (EESB) on spatial memory function and neurogenesis in the hippocampal dentate gyrus. Adult Sprague-Dawley rats were orally administered 50, 100, or 200 mg/kg of EESB for 6 successive days. The radial-arm maze test showed that 200 mg/kg of EESB improved the spatial memory of adult rats. Confocal microscopy results showed that 100 mg/kg of EESB increased the number of bromodeoxyuridine (BrdU)- and neuron-specific nuclear protein-positive cells in the granular cell layer, and that 100 and 200 mg/kg of EESB increased the number of BrdU-/neuron-specific nuclear protein-positive cells in the sub-granular zone. 200 mg/kg of EESB increased the number of BrdU-/glial fibrillary acid protein-positive cells in the subgranular zone. These findings indicate that EESB can effectively promote neurogenesis in the hippocampal dentate gyrus and improve spatial memory function.

  5. Novel Control by the CA3 Region of the Hippocampus on Neurogenesis in the Dentate Gyrus of the Adult Rat

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    Jian Xin Liu; Pinnock, Scarlett B.; Joe Herbert

    2011-01-01

    The dentate gyrus is a site of continued neurogenesis in the adult brain. The CA3 region of the hippocampus is the major projection area from the dentate gyrus. CA3 sends reciprocal projections back to the dentate gyrus. Does this imply that CA3 exerts some control over neurogenesis? We studied the effects of lesions of CA3 on neurogenesis in the dentate gyrus, and on the ability of fluoxetine to stimulate mitotic activity in the progenitor cells. Unilateral ibotenic-acid generated lesions we...

  6. Gene expression profiling of the hippocampal dentate gyrus in an adult toxicity study captures a variety of neurodevelopmental dysfunctions in rat models of hypothyroidism.

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    Shiraki, Ayako; Saito, Fumiyo; Akane, Hirotoshi; Akahori, Yumi; Imatanaka, Nobuya; Itahashi, Megu; Yoshida, Toshinori; Shibutani, Makoto

    2016-01-01

    We previously found that developmental hypothyroidism changed the expression of genes in the rat hippocampal dentate gyrus, a brain region where adult neurogenesis is known to occur. In the present study, we performed brain region-specific global gene expression profiling in an adult rat hypothyroidism model to see if it reflected the developmental neurotoxicity we saw in the developmental hypothyroidism model. Starting when male rats were 5 weeks old, we administered 6-propyl-2-thiouracil at a doses of 0, 0.1 and 10 mg kg(-1) body weight by gavage for 28 days. We selected four brain regions to represent both cerebral and cerebellar tissues: hippocampal dentate gyrus, cerebral cortex, corpus callosum and cerebellar vermis. We observed significant alterations in the expression of genes related to neural development (Eph family genes and Robo3) in the cerebral cortex and hippocampal dentate gyrus and in the expression of genes related to myelination (Plp1 and Mbp) in the hippocampal dentate gyrus. We observed only minor changes in the expression of these genes in the corpus callosum and cerebellar vermis. We used real-time reverse-transcription polymerase chain reaction to confirm Chrdl1, Hes5, Mbp, Plp1, Slit1, Robo3 and the Eph family transcript expression changes. The most significant changes in gene expression were found in the dentate gyrus. Considering that the gene expression profile of the adult dentate gyrus closely related to neurogenesis, 28-day toxicity studies looking at gene expression changes in adult hippocampal dentate gyrus may also detect possible developmental neurotoxic effects.

  7. Prolonged protein deprivation differentially affects calretinin- and parvalbumin-containing interneurons in the hippocampal dentate gyrus of adult rats.

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    Hipólito-Reis, José; Pereira, Pedro Alberto; Andrade, José Paulo; Cardoso, Armando

    2013-10-25

    Protein deprivation is a detrimental nutritional state that induces several deleterious changes in the rat hippocampal formation. In this study, we compared the effects of protein deprivation in the number of parvalbumin (PV)-immunoreactive and calretinin (CR)-immunoreactive interneurons of the dentate gyrus, which are involved in the control of calcium homeostasis and fine tuning of the hippocampal circuits. Two month-old rats were randomly assigned to control and low-protein diet groups. The rats of the latter group were fed with a low-protein diet (8% casein) for 6 months. All animals were perfused at 8 months of age. The number of neurons expressing CR in the molecular layer and in the hilus of dentate gyrus was reduced in protein-deprived rats. Conversely, protein deprivation increased the number of PV-containing interneurons in the dentate granule cell layer and hilus. These results support the view that protein deprivation may disturb calcium homeostasis, leading to neuronal death including GABAergic interneurons expressing CR. In the other hand, the up-regulation of PV cells may reflect a protective mechanism to counteract the calcium overload and protect the remaining neurons of the dentate gyrus.

  8. Effects of butternut squash extract on dentate gyrus cell proliferation and spatial learning in male adult rats

    Institute of Scientific and Technical Information of China (English)

    Mohsen Marzban; Sara Soleimani Asl; Hassan Fallah Huseini; Mahdi Tondar; Samira Choopani; Mehdi Mehdizadeh

    2011-01-01

    Previous studies reported that some plants, including butternut squash, exert positive effects on the brain. However, few studies have examined the effects of butternut squash on learning, memory, and neurogenesis. This study studied the effects of butternut squash extract on spatial learning and cell proliferation in the dentate gyrus of healthy male rats. Thirty-five male Wistar rats were intrap-eritoneally injected with 0, 50, 100, 200 and 400 mg/kg butternut squash extract once daily for 2 months. After the last administration, rat's spatial memory was studied using the Morris water maze. Finally, rats were sacrificed and hippocampal sections were prepared for light microscopy and bromodeoxyuridine immunohistochemistry studies. The results revealed that escape latency and swim distance decreased in all treatment groups compared with the control rats, and that the number of bromodeoxyuridine-positive cells in the dentate gyrus was significantly increased in the treatment groups compared with the controls. These findings suggest that butternut squash extract improves the learning and memory abilities of male rats, and increases the proliferation of dentate gyrus cells.

  9. Caffeine and modafinil promote adult neuronal cell proliferation during 48 h of total sleep deprivation in rat dentate gyrus.

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    Sahu, Surajit; Kauser, Hina; Ray, Koushik; Kishore, Krishna; Kumar, Sanjeev; Panjwani, Usha

    2013-10-01

    It has been established that sleep deprivation (SD) reduces the proliferation of neuronal precursors in the adult hippocampus. It has also been reported that psychostimulant drugs modulate adult neurogenesis. We examined the modulatory role of two psychostimulant drugs modafinil and caffeine on adult neuronal cell proliferation (NCP) during 48 h of total SD. A novel automated cage shaking stimulus was used to induce SD based on animal activity. 5-Bromo-2″-deoxyuridine (BrdU; 50mg/kg/day i.p.) was injected at the onset of the light phase for two days. Rats were successfully sleep deprived for 85-94% of total time. Stereological analysis showed that both caffeine and modafinil treatments during SD improved the number of BrdU positive cells as compared to the SD group. Caffeine treatment during SD, significantly increased early proliferative and post-mitotic stages of doublecortin (DCX) positive cells while modafinil treatment during SD, increased intermediate and post-mitotic stages of DCX positive cells compared to SD+Vehicle group. Brain-Derived Neurotrophic Factor (BDNF) expression on BrdU positive cells as well as in the dentate gyrus (DG) region was decreased significantly after sleep deprivation. Both caffeine and modafinil significantly improved BDNF expression in the DG region. Modafinil, but not caffeine, significantly decreased hippocampal adenosine level during SD in comparison to the SD+Vehicle group. It may be concluded that caffeine or modafinil treatment during 48 h of SD prevents the SD induced decline in neuronal proliferation and differentiation. Caffeine and modafinil induced alterations of NCP during SD may involve modulation of BDNF and adenosine levels.

  10. Ketogenic diets cause opposing changes in synaptic morphology in CA1 hippocampus and dentate gyrus of late-adult rats.

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    Balietti, Marta; Giorgetti, Belinda; Fattoretti, Patrizia; Grossi, Yessica; Di Stefano, Giuseppina; Casoli, Tiziana; Platano, Daniela; Solazzi, Moreno; Orlando, Fiorenza; Aicardi, Giorgio; Bertoni-Freddari, Carlo

    2008-06-01

    Ketogenic diets (KDs) have beneficial effects on several diseases, such as epilepsy, mitochondriopathies, cancer, and neurodegeneration. However, little is known about their effects on aging individuals. In the present study, late-adult (19-month-old) rats were fed for 8 weeks with two medium chain triglycerides (MCT)-KDs, and the following morphologic parameters reflecting synaptic plasticity were evaluated in stratum moleculare of hippocampal CA1 region (SM CA1) and outer molecular layer of hippocampal dentate gyrus (OML DG): average area (S), numeric density (Nv(s)), and surface density (Sv) of synapses, and average volume (V), numeric density (Nv(m)), and volume density (Vv) of synaptic mitochondria. In SM CA1, MCT-KDs induced the early appearance of the morphologic patterns typical of old animals (higher S and V, and lower Nv(s) and Nv(m)). On the contrary, in OML DG, Sv and Vv of MCT-KDs-fed rats were higher (as a result of higher Nv(s) and Nv(m)) versus controls; these modifications are known to improve synaptic function and metabolic supply. The opposite effects of MCT-KDs might reflect the different susceptibility to aging processes: OML DG is less vulnerable than SM CA1, and the reactivation of ketone bodies uptake and catabolism might occur more efficiently in this region, allowing the exploitation of their peculiar metabolic properties. Present findings provide the first evidence that MCT-KDs may cause opposite morphologic modifications, being potentially harmful for SM CA1 and potentially advantageous for OML DG. This implies risks but also promising potentialities for their therapeutic use during aging.

  11. Dentate Gyrus-Specific Knockdown of Adult Neurogenesis Impairs Spatial and Object Recognition Memory in Adult Rats

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    Jessberger, Sebastian; Clark, Robert E.; Broadbent, Nicola J.; Clemenson, Gregory D., Jr.; Consiglio, Antonella; Lie, D. Chichung; Squire, Larry R.; Gage, Fred H.

    2009-01-01

    New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons…

  12. Prolonged protein deprivation, but not food restriction, affects parvalbumin-containing interneurons in the dentate gyrus of adult rats.

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    Cardoso, Armando; Castro, João Paulo; Pereira, Pedro Alberto; Andrade, José Paulo

    2013-07-19

    Several studies have demonstrated the vulnerability of the hippocampal formation to malnutrition. In this study, we compared the effects of food restriction and protein malnutrition in the total number of neurons of the dentate gyrus and in the number of parvalbumin-immunoreactive (PV-IR) interneurons, which are related to the control of calcium homeostasis and fine tuning of the hippocampal circuits. Two month-old rats were randomly assigned to control, food-restricted and low-protein diet groups. After 6 months, 10 rats from the low-protein diet group were selected at random and fed with a normal protein diet for 2 months. The total number of granule and hilar cells was reduced in protein-deprived rats and the nutritional reestablishment with a normal protein diet did not recover neuron numbers. Protein deprivation increased the number of PV-IR interneurons in the granule cell layer and hilus, but their number returned to values similar to controls after nutritional rehabilitation. Food restriction did not affect the total number of neurons or the density of PV-IR interneurons in the dentate gyrus. These results support the view that protein deprivation may disturb calcium homeostasis, leading to neuronal death. The up-regulation of PV-IR cells may reflect a protective mechanism to counteract the calcium overload and protect the remaining neurons of the dentate gyrus. This imbalance in cell-ratio favoring GABAergic interneurons may justify some learning and memory impairments described in protein-deprived animals. This contrast between the results of food restriction and protein deprivation should be further analyzed in future studies.

  13. Physical exercise and environment exploration affect synaptogenesis in adult-generated neurons in the rat dentate gyrus: possible role of BDNF.

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    Ambrogini, P; Lattanzi, D; Ciuffoli, S; Betti, M; Fanelli, M; Cuppini, R

    2013-10-09

    A brief training in a pool maze, with or without cognitive tasks, modifies the synaptogenesis and maturation of newborn neurons in adult rat dentate gyrus. These types of trainings have many aspects, including physical activity and exploration. Therefore, to evaluate whether physical exercise and environment exploration are able to affect synapse formation and the maturation of adult-generated neurons, GFP-retrovirus infusion was performed on rats which, on the fourth day after injection, were housed under running conditions or allowed to explore an enriched environment briefly in the absence of exercise for the following three days. Afterward, at the end of the trainings, electrophysiological and morphological studies were conducted. Considering that neurotrophic factors increase after exercise or environment exploration, hippocampal BDNF levels and TrkB receptor activation were evaluated. In this study, we show that both spontaneous physical activity and enriched environment exploration induced synaptogenesis and T-type voltage-dependent Ca(2+) currents in very immature neurons. Hippocampal BDNF levels and TrkB receptor activation were determined to be increasing following physical activity and exploration. A possible contribution of BDNF signaling in mediating the observed effects was supported by the use of 7-8-dihydroxyflavone, a selective TrkB agonist, and of ANA-12, an inhibitor of TrkB receptors.

  14. Effects of exercise on neurogenesis in the dentate gyrus and ability of learning and memory after hippocampus lesion in adult rats

    Institute of Scientific and Technical Information of China (English)

    Lin CHEN; Shan GONG; Li-Dong SHAN; Wei-Ping XU; Yue-Jin ZHANG; Shi-Yu GUO; Tadashi Hisamitsu; Qi-Zhang YIN; Xing-Hong JIANG

    2006-01-01

    Objective To explore the effects of exercise on dentate gyrus (DG) neurogenesis and the ability of learning and memory in hippocampus-lesioned adult rats. Methods Hippocampus lesion was produced by intrahippocampal microinjection of kainic acid (KA). Bromodeoxyuridine (BrdU) was used to label dividing cells. Y maze test was used to evaluate the ability of learning and memory. Exercise was conducted in the form of forced running in a motor-driven running wheel. The speed of wheel revolution was regulated at 3 kinds of intensity: lightly running, moderately running, or heavily running. Results Hippocampus lesion could increase the number of BrdU-labeled DG cells, moderately running after lesion could further enhance the number of BrdU-labeled cells and decrease the error number (EN) in Y maze test,while neither lightly running, nor heavily running had such effects. There was a negative correlation between the number of DG BrdU-labeled cells and the EN in the Y maze test after running. Conclusion Moderate exercise could enhance the DG neurogenesis and ameliorate the ability of learning and memory in hippocampus-lesioned rats.

  15. Temporal changes in prosaposin expression in the rat dentate gyrus after birth.

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    Midori Morishita

    Full Text Available Neurogenesis in the hippocampal dentate gyrus occurs constitutively throughout postnatal life. Adult neurogenesis includes a multistep process that ends with the formation of a postmitotic and functionally integrated new neuron. During adult neurogenesis, various markers are expressed, including GFAP, nestin, Pax6, polysialic acid-neural cell adhesion molecule (PSA-NCAM, neuronal nuclei (NeuN, doublecortin, TUC-4, Tuj-1, and calretinin. Prosaposin is the precursor of saposins A-D; it is found in various organs and can be excreted. Strong prosaposin expression has been demonstrated in the developing brain including the hippocampus, and its neurotrophic activity has been proposed. This study investigated changes in prosaposin in the dentate gyrus of young and adult rats using double immunohistochemistry with antibodies to prosaposin, PSA-NCAM, and NeuN. Prosaposin immunoreactivity was intense in the dentate gyrus at postnatal day 3 (P3 and P7, but decreased gradually after P14. In the dentate gyrus at P28, immature PSA-NCAM-positive neurons localized exclusively in the subgranular zone were prosaposin-negative, whereas mature Neu-N-positive neurons were positive for prosaposin. Furthermore, these prosaposin-negative immature neurons were saposin B-positive, suggesting that the neurons take up and degrade prosaposin. In situ hybridization assays showed that prosaposin in the adult dentate gyrus is dominantly the Pro+9 type, a secreted type of prosaposin. These results imply that prosaposin secreted from mature neurons stimulates proliferation and maturation of immature neurons in the dentate gyrus.

  16. Adult neurogenesis in the intact and epileptic dentate gyrus.

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    Parent, Jack M

    2007-01-01

    Neurogenesis persists throughout life in the adult mammalian dentate gyrus. Adult-born dentate granule cells integrate into existing hippocampal circuitry and may provide network plasticity necessary for certain forms of hippocampus-dependent learning and memory. Neural stem cells and neurogenesis in the adult dentate gyrus are regulated by a variety of environmental, physiological, and molecular factors. These include aging, stress, exercise, neurovascular components of the stem cell niche, growth factors, neurotransmitters, and hormones. Seizure activity also influences dentate granule cell neurogenesis. Production of adult-born neurons increases in rodent models of temporal lobe epilepsy, and both newborn and pre-existing granule neurons contribute to aberrant axonal reorganization in the epileptic hippocampus. Prolonged seizures also disrupt the migration of dentate granule cell progenitors and lead to hilar-ectopic granule cells. The ectopic granule neurons appear to integrate abnormally and contribute to network hyperexcitability. Similar findings of granule cell layer dispersion and ectopic granule neurons in human TLE suggest that aberrant neurogenesis contributes to epileptogenesis or learning and memory disturbances in this epilepsy syndrome.

  17. Adult neurogenesis modifies excitability of the dentate gyrus

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    Taruna eIkrar

    2013-12-01

    Full Text Available Adult-born dentate granule neurons contribute to memory encoding functions of the dentate gyrus (DG such as pattern separation. However, local circuit-mechanisms by which adult-born neurons partake in this process are poorly understood. Computational, neuroanatomical and electrophysiological studies suggest that sparseness of activation in the granule cell layer (GCL is conducive for pattern separation. A sparse coding scheme is thought to facilitate the distribution of similar entorhinal inputs across the GCL to decorrelate overlapping representations and minimize interference. Here we used fast voltage-sensitive dye (VSD imaging combined with laser photostimulation and electrical stimulation to examine how selectively increasing adult DG neurogenesis influences local circuit activity and excitability. We show that DG of mice with more adult-born neurons exhibits decreased strength of neuronal activation and more restricted excitation spread in GCL while maintaining effective output to CA3c. Conversely, blockade of adult hippocampal neurogenesis changed excitability of the DG in the opposite direction. Analysis of GABAergic inhibition onto mature dentate granule neurons in the DG of mice with more adult-born neurons shows a modest readjustment of perisomatic inhibitory synaptic gain without changes in overall inhibitory tone, presynaptic properties or GABAergic innervation pattern. Retroviral labeling of connectivity in mice with more adult-born neurons showed increased number of excitatory synaptic contacts of adult-born neurons onto hilar interneurons. Together, these studies demonstrate that adult hippocampal neurogenesis modifies excitability of mature dentate granule neurons and that this non-cell autonomous effect may be mediated by local circuit mechanisms such as excitatory drive onto hilar interneurons. Modulation of DG excitability by adult-born dentate granule neurons may enhance sparse coding in the GCL to influence pattern

  18. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

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    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  19. Experimental hypothyroidism delays field excitatory post-synaptic potentials and disrupts hippocampal long-term potentiation in the dentate gyrus of hippocampal formation and Y-maze performance in adult rats.

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    Artis, A S; Bitiktas, S; Taşkın, E; Dolu, N; Liman, N; Suer, C

    2012-03-01

    Manipulations of thyroid hormones have been shown to influence learning and memory. Although a large body of literature is available on the effect of thyroid hormone deficiency on learning and memory functions during the developmental stage, electrophysiological and behavioural findings, particularly on propylthiouracil administration to adult normothyroid animals, are not satisfactory. The experiments in the present study were carried out on 12 adult male Wistar rats aged 6-7 months. Hypothyroidism was induced by administering 6-n-propyl-2-thiouracil in their drinking water for 21 days at a concentration of 0.05%. The spatial learning performance of hypothyroid and control rats was studied on a Y-maze. The rats were then placed in a stereotaxic frame under urethane anaesthesia. A bipolar tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted into the granule cell layer of the ipsilateral dentate gyrus to record field excitatory post-synaptic potentials. After a 15-min baseline recording of field potentials, long-term potentiation was induced by four sets of tetanic trains. The propylthiouracil-treated rats showed a significantly attenuated input-output (I/O) relationship when population spike (PS) amplitudes and field excitatory post-synaptic potentials (fEPSP) were compared. fEPSP and PS latencies were found to be longer in the hypothyroid group than in the control group. The PS amplitude and fEPSP slope potentiations in the hypothyroid rats were not statistically different from those in the control rats, except for the field EPSP slope measured in the post-tetanic and maintenance phases. The hypothyroid rats also showed lower thyroxine levels and poor performance in the spatial memory task. The present study provides in vivo evidence for the action of propylthiouracil leading to impaired synaptic plasticity, which might explain deficit in spatial memory tasks in adult hypothyroid rats.

  20. Propylthiouracil (PTU)-induced hypothyroidism in the developing rat impairs synaptic transmission and plasticity in the dentate gyrus of the adult hippocampus.

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    Gilbert, M E; Paczkowski, C

    2003-10-10

    Reductions in thyroid hormone during critical periods of brain development can have devastating effects on neurological function that are permanent. Neurochemical, molecular and structural alterations in a variety of brain regions have been well documented, but little information is available on the consequences of developmental hypothyroidism on synaptic function. Developing rats were exposed to the thyrotoxicant, propylthiouracil (PTU: 0 or 15 ppm), through the drinking water of pregnant dams beginning on GD18 and extending throughout the lactational period. Male offspring were allowed to mature after termination of PTU exposure at weaning on PND21 and electrophyiological assessments of field potentials in the dentate gyrus were conducted under urethane anesthesia between 2 and 5 months of age. PTU dramatically reduced thyroid hormones on PND21 and produced deficits in body weight that persisted to adulthood. Synaptic transmission was impaired as evidenced by reductions in excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitudes at a range of stimulus intensities. Long-term potentiation of the EPSP slope was impaired at both modest and strong intensity trains, whereas a paradoxical increase in PS amplitude was observed in PTU-treated animals in response to high intensity trains. These data are the first to describe functional impairments in synaptic transmission and plasticity in situ as a result of PTU treatment and suggest that perturbations in synaptic function may contribute to learning deficits associated with developmental hypothyroidism.

  1. Differential expression of cytoskeletal proteins in the dendrites of parvalbumin-positive interneurons versus granule cells in the adult rat dentate gyrus.

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    de Haas Ratzliff, A; Soltesz, I

    2000-01-01

    Parvalbumin-positive interneurons and granule cells of the dentate gyrus exhibit characteristic differences in morphological, cytochemical, physiological, and pathophysiological properties. Several of these defining features, including dendritic morphology, spine density, and sensitivity to insults, are likely to be influenced by the neuronal cytoskeleton. The data in this paper demonstrate striking differences in the expression levels of all three neurofilament triplet proteins, as well as alpha-internexin and beta-tubulin III, between the parvalbumin-positive interneurons and dentate granule cells. Therefore, the molecular composition of intermediate filaments and microtubules in the dendritic domain of parvalbumin-positive dentate interneurons is distinct from the cytoskeleton of neighboring granule cells, indicating the existence of highly cell type-specific cytoskeletal architecture within the dentate gyrus.

  2. 成年和老年大鼠脑出血后海马齿状回神经干细胞增殖分化的比较%Proliferation and differentiation of neural stem cells in hippocampus dentate gyrus in adult and aged rats after intracerebral hemorrhage

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    文玉军; 王登科; 孙征; 刘海洋; 张莲香; 王效军; 秦毅

    2012-01-01

    Objective To investigate the difference of the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus dentate gyrus between adult and aged rats after intracerebral hemorrhage (ICH), to explore the variation of NSCs after ICH. Methods ICH models were established by injecting collagenase Ⅶ into the brain of rats. Proliferating cells were labeled by BrdU abdominal cavity injection. Immunohistochemical single and double staining with antibodies against BrdU, NeuN and GFAP were used to determine proliferation and differentiation of hippocampus dentate gyrus. Results In non-ICH rats, BrdU positive cells in hippocampus dentate gyrus of adult rats were much more than those of aged rats. After ICH, BrdU positive cells in hippocampus dentate gyrus of rats were significantly increased. 7 d group rats had reached its peak. BrdU positive cells in hippocampus dentate gyrus of adult rats were much more than those of aged rats all the time. In non-ICH rats, a little of BrdU/NeuN and BrdU/GFAP double positive cells were found in the hippocampus dentate gyrus. After ICH, the quantity of double positive cells were increased obviously. BrdU/GFAP double positive cells of aged rats were much more than those of adult rats, but BrdU/NeuN double positive cells of aged rats were less than those of adult rats. Conclusions After ICH, NSCs in hippocampus dentate gyrus of rats are activated. Proliferation and differentiation of NSCs in hippocampus dentate gyrus of adult rats are stronger than those of aged rats.%目的 比较成年和老年大鼠脑出血后海马齿状回神经干细胞(NSCs)的增殖与分化,探讨脑出血后NSCs的变化规律.方法 制作大鼠脑出血模型,5-溴脱氧尿核苷(BrdU)腹腔注射标记增殖细胞,用免疫组化法检测大鼠海马齿状回BrdU、神经元核抗原(NeuN)、胶质纤维酸性蛋白(GFAP)阳性细胞数的变化.结果 正常组和假手术组大鼠海马齿状回均可见BrdU阳性细胞,成年大鼠明显

  3. Developmental hypothyroidism abolishes bilateral differences in sonic hedgehog gene control in the rat hippocampal dentate gyrus.

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    Tanaka, Takeshi; Wang, Liyun; Kimura, Masayuki; Abe, Hajime; Mizukami, Sayaka; Yoshida, Toshinori; Shibutani, Makoto

    2015-03-01

    Both developmental and adult-stage hypothyroidism disrupt rat hippocampal neurogenesis. We previously showed that exposing mouse offspring to manganese permanently disrupts hippocampal neurogenesis and abolishes the asymmetric distribution of cells expressing Mid1, a molecule regulated by sonic hedgehog (Shh) signaling. The present study examined the involvement of Shh signaling on the disruption of hippocampal neurogenesis in rats with hypothyroidism. Pregnant rats were treated with methimazole (MMI) at 0 or 200 ppm in the drinking water from gestation day 10-21 days after delivery (developmental hypothyroidism). Adult male rats were treated with MMI in the same manner from postnatal day (PND) 46 to PND 77 (adult-stage hypothyroidism). Developmental hypothyroidism reduced the number of Mid1(+) cells within the subgranular zone of the dentate gyrus of offspring on PND 21, and consequently abolished the normal asymmetric predominance of Mid1(+) cells on the right side through the adult stage. In control animals, Shh was expressed in a subpopulation of hilar neurons, showing asymmetric distribution with left side predominance on PND 21; however, this asymmetry did not continue through the adult stage. Developmental hypothyroidism increased Shh(+) neurons bilaterally and abolished the asymmetric distribution pattern on PND 21. Adult hypothyroidism also disrupted the asymmetric distribution of Mid1(+) cells but did not affect the distribution of Shh(+) hilar neurons. The results suggest that the hippocampal neurogenesis disruption seen in hypothyroidism involves changes in asymmetric Shh(+) neuron distribution in developmental hypothyroidism and altered Mid1 expression in both developmental and adult-stage hypothyroidism.

  4. Analyzing dendritic growth in a population of immature neurons in the adult dentate gyrus using laminar quantification of disjointed dendrites

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    Shira eRosenzweig

    2011-03-01

    Full Text Available In the dentate gyrus of the hippocampus, new granule neurons are continuously produced throughout adult life. A prerequisite for the successful synaptic integration of these neurons is the sprouting and extension of dendrites into the molecular layer of the dentate gyrus. Thus, studies aimed at investigating the developmental stages of adult neurogenesis often use dendritic growth as an important indicator of neuronal health and maturity. Based on the known topography of the dentate gyrus, characterized by distinct laminar arrangement of granule neurons and their extensions, we have developed a new method for analysis of dendritic growth in immature adult-born granule neurons. The method is comprised of laminar quantification of cell bodies, primary, secondary and tertiary dendrites separately and independently from each other. In contrast to most existing methods, laminar quantification of dendrites does not require the use of exogenous markers and does not involve arbitrary selection of individual neurons. The new method relies on immonuhistochemical detection of endogenous markers such as doublecortin to perform a comprehensive analysis of a sub-population of immature neurons. Disjointed, orphan dendrites that often appear in the thin histological sections are taken into account. Using several experimental groups of rats and mice, we demonstrate here the suitable techniques for quantifying neurons and dendrites, and explain how the ratios between the quantified values can be used in a comparative analysis to indicate variations in dendritic growth and complexity.

  5. Relationship between chewing behavior and body weight status in fully dentate healthy adults.

    Science.gov (United States)

    Zhu, Yong; Hollis, James H

    2015-03-01

    Recent research indicates that chewing behavior may influence energy intake and energy expenditure. However, little is known about the relationship between chewing behavior and body weight status. In the present study, 64 fully dentate normal-weight or overweight/obese adults were asked to consume five portions of a test food and the number of chewing cycles, chewing duration before swallowing and chewing rate were measured. Adjusting for age and gender, normal-weight participants used a higher number of chewing cycles (p = 0.003) and a longer chewing duration (p weight status in fully dentate healthy adults.

  6. Tooth loss inhibits neurogenesis in the dentate gyrus of adult mice

    Institute of Scientific and Technical Information of China (English)

    Shaochen Su; Tao Qi; Baoli Su; Huibin Gu; Jianlin Wang; Lan Yang

    2014-01-01

    Tooth loss has been shown to affect learning and memory in mice and increases the risk of Alz-heimer’s disease. The dentate gyrus is strongly associated with cognitive function. This study hypothesized that tooth loss affects neurons in the dentate gyrus. Adult male mice were random-ly assigned to either the tooth loss group or normal control group. In the tooth loss group, the left maxillary and mandibular molars were extracted. Normal control mice did not receive any intervention. Immunolfuorescence staining revealed that the density and absorbance of double-cortin-and neuronal nuclear antigen-positive cells were lower in the tooth loss group than in the normal control group. These data suggest that tooth loss may inhibit neurogenesis in the dentate gyrus of adult mice.

  7. Stereotactic injection of cerebrospinal fluid from anti-NMDA receptor encephalitis into rat dentate gyrus impairs NMDA receptor function.

    Science.gov (United States)

    Würdemann, Till; Kersten, Maxi; Tokay, Tursonjan; Guli, Xiati; Kober, Maria; Rohde, Marco; Porath, Katrin; Sellmann, Tina; Bien, Christian G; Köhling, Rüdiger; Kirschstein, Timo

    2016-02-15

    Autoimmune encephalitis is increasingly recognized in patients with otherwise unexplained encephalopathy with epilepsy. Among these, patients with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis present epileptic seizures, memory deficits, and psychiatric symptoms. However, the functional consequences of such autoantibodies are poorly understood. In order to investigate the pathophysiology of this disease, we stereotactically injected either cerebrospinal fluid (CSF) from three anti-NMDAR encephalitis patients or commercially available anti-NMDAR1 into the dentate gyrus of adult female rats. Control animals were injected with either CSF obtained from three epilepsy patients (ganglioglioma, posttraumatic epilepsy, focal cortical dysplasia) lacking anti-NMDAR or saline. Intracellular recordings from dentate gyrus granule cells showed a significant reduction of the NMDAR-evoked excitatory postsynaptic potentials (NMDAR-EPSPs) in animals treated with anti-NMDAR. As a consequence of this, action potential firing in these cells by NMDAR-EPSPs was significantly impaired. Long-term potentiation in the dentate gyrus was also significantly reduced in rats injected with anti-NMDAR as compared to control animals. This was accompanied by a significantly impaired learning performance in the Morris water maze hidden platform task when the animals had been injected with anti-NMDAR antibody-containing CSF. Our findings suggest that anti-NMDAR lead to reduced NMDAR function in vivo which could contribute to the memory impairment found in patients with anti-NMDAR encephalitis.

  8. Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus.

    Science.gov (United States)

    Fukuda, Satoshi; Kato, Fusao; Tozuka, Yusuke; Yamaguchi, Masahiro; Miyamoto, Yusei; Hisatsune, Tatsuhiro

    2003-10-15

    Neurogenesis in the dentate gyrus of the adult mammalian hippocampus has been proven in a series of studies, but the differentiation process toward newborn neurons is still unclear. In addition to the immunohistochemical study, electrophysiological membrane recordings of precursor cells could provide an alternative view to address this differentiation process. In this study, we performed green fluorescent protein (GFP)-guided selective recordings of nestin-positive progenitor cells in adult dentate gyrus by means of nestin-promoter GFP transgenic mice, because nestin is a typical marker for precursor cells in the adult dentate gyrus. The patch-clamp recordings clearly demonstrated the presence of two distinct subpopulations (type I and type II) of nestin-positive cells. Type I cells had a lower input resistance value of 77.1 M(Omega) (geometric mean), and their radial processes were stained with anti-glial fibrillary acidic protein antibody. On the other hand, type II nestin-positive cells had a higher input resistance value of 2110 MOmega and expressed voltage-dependent sodium current. In most cases, type II cells were stained with anti-polysialylated neural cell adhesion molecule. Taken together with a bromodeoxyuridine pulse-chase analysis, our results may reflect a rapid and dynamic cell conversion of nestin-positive progenitor, from type I to type II, at an early stage of adult neurogenesis in the dentate gyrus.

  9. Expression of glutamic acid decarboxylase and identification of GABAergic cells in the ischemic rat dentate gyrus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Dogonowski, Anne-Marie; Finsen, Bente;

    2006-01-01

    We have investigated the glutamic acid dexcarboxylase (GAD) mRNA and protein isoforms as markers for ischemic loss of GABAergic neurons in the dentate hilus. Stereological counts of these neurons were performed in rats surviving 8 days after 10 min of transient forebrain ischemia, and in control...

  10. Expression of glutamic acid decarboxylase and identification of GABAergic cells in the ischemic rat dentate gyrus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Dogonowski, Anne-Marie; Finsen, Bente;

    2006-01-01

    We have investigated the glutamic acid dexarboxylase (GAD) mRNA and protein isoforms as markers for ischemic loss of GABAergic neurons in the dentate hilus. Stereological counts of these neurons were performed in rats surviving 8 days after 10 min of transient forebrain ischemia, and in control...

  11. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus.

    Science.gov (United States)

    van Praag, H; Kempermann, G; Gage, F H

    1999-03-01

    Exposure to an enriched environment increases neurogenesis in the dentate gyrus of adult rodents. Environmental enrichment, however, typically consists of many components, such as expanded learning opportunities, increased social interaction, more physical activity and larger housing. We attempted to separate components by assigning adult mice to various conditions: water-maze learning (learner), swim-time-yoked control (swimmer), voluntary wheel running (runner), and enriched (enriched) and standard housing (control) groups. Neither maze training nor yoked swimming had any effect on bromodeoxyuridine (BrdU)-positive cell number. However, running doubled the number of surviving newborn cells, in amounts similar to enrichment conditions. Our findings demonstrate that voluntary exercise is sufficient for enhanced neurogenesis in the adult mouse dentate gyrus.

  12. Evaluation of Spirulina Supplementation on Intermittent Binge Ethanol - Induced Neurotoxicity in Dentate Gyrus of Rats

    Directory of Open Access Journals (Sweden)

    M A Asari

    2013-03-01

    Full Text Available Summary. Spirulina is a widely used nutritional supplement which is rich in antioxidants and proteins.  Studies have shown that intermittent binge-like ethanol consumption during adolescent period caused neuronal damage in specific parts of the brain, including the dentate gyrus. It has been suggested that antioxidant therapy may provide some level of protection against neurotoxicity of ethanol at cellular level. Therefore, the purpose of this study was to examine the preventive effects of spirulina supplementation on ethanol-induced neurotoxicity in the dentate gyrus of adolescent rats. Male Sprague-Dawley rats were given ethanol (10 g/kg/day, intermittent binge model, or spirulina platensis (1000 mg/kg/day or both from postnatal day 30 for two weeks duration. The cerebral hemispheres were processed for routine histological staining and immunohistochemistry with anti-GFAP antibody.  Ethanol-treated group showed significant deficit in the numbers of granule cells and hilar neurons of the dentate gyrus when compared to the control group. Spirulina supplementation failed to provide protection against ethanol-induced neuronal loss. Spirulina supplementation also failed to alter increased expression of GFAP immunoreactivity induced by ethanol exposure. In conclusion, these findings indicate that spirulina supplementation is not effective in reducing the ethanol-induced neurotoxicity in the dentate gyrus of adolescent rats. Industrial Relevance. Spirulina is one of the widely used nutritional supplements particularly in Asian population. Being a strong antioxidant, spirulina has been shown to have many therapeutic effects in human. However, the question of whether spirulina supplementation is able to mitigate the effect of ethanol neurotoxicity is largely unknown. Therefore, the study was undertaken to investigate the possibility that spirulina supplementation is able to provide some protection against ethanol-induced neurotoxicity in a rat model

  13. The similarity of astrocytes number in dentate gyrus and CA3 subfield of rats hippocampus.

    Science.gov (United States)

    Jahanshahi, Mehrdad; Sadeghi, Y; Hosseini, A; Naghdi, N

    2007-01-01

    The dentate gyrus is a part of hippocampal formation that it contains granule cells, which project to the pyramidal cells and interneurons of the CA3 subfield of the hippocampus. Astrocytes play a more active role in neuronal activity, including regulating ion flux currents, energy production, neurotransmitter release and synaptogenesis. Astrocytes are the only cells in the brain that contain the energy molecule glycogen. The close relationship between dentate gyrus and CA3 area can cause the similarity of the number of astrocytes in these areas. In this study 5 male albino wistar rats were used. Rats were housed in large plastic cage in animal house and were maintained under standard conditions, after histological processing, The 7 microm slides of the brains were stained with PTAH staining for showing the astrocytes. This staining is specialized for astrocytes. We showed that the number of astrocytes in different (ant., mid., post) parts of dentate gyrus and CA3 of hippocampus is the same. For example, the anterior parts of two area have the most number of astrocytes and the middle parts of two area have the least number of astrocytes. We concluded that dentate gyrus and CA3 area of hippocampus have the same group of astrocytes.

  14. The effect of amygdala kindling on hippocampal neurogenesis coincides with decreased reelin and DISC1 expression in the adult dentate gyrus.

    Science.gov (United States)

    Fournier, N M; Andersen, D R; Botterill, J J; Sterner, E Y; Lussier, A L; Caruncho, H J; Kalynchuk, L E

    2010-05-01

    Temporal lobe seizures can induce the proliferation and abnormal migration of newly generated dentate granule cells, but little is known about the molecular mechanisms that govern these pathological events. Reelin and DISC1 (disrupted-in-schizophrenia 1) are proteins that play a regulatory role in the maturation and integration of new neurons in the developing and adult brain. In this study, we examined whether amygdala kindling results in aberrant neurogenesis and altered expression of reelin and DISC1 in the adult dentate gyrus. Using doublecortin immunohistochemistry, we found that short-term kindling (i.e., 30 electrical stimulations) significantly increased the number of immature neurons in the dentate subgranular zone (SGZ), whereas long-term kindling (i.e., 99 electrical stimulations) did not. However, doublecortin-labeled neurons in long-term kindled rats showed greater dendritic complexity than they did in short-term kindled or control rats. We also found that long-term kindling decreased the number of reelin-positive cells and decreased DISC1 expression in the dentate granule cell layer and subgranular zone. Interestingly, kindling-induced changes in reelin and DISC1 expression coincided with the appearance of ectopically located Prox1-labeled granule cells in the hilus. These effects occurred independently of alterations in granule cell layer length, dentate volume, or the number of hilar neurons. Taken together, these findings suggest a novel role for DISC1 in the pathophysiology of temporal lobe epilepsy and further suggest that changes in reelin and DISC1 expression may contribute to aberrant neurogenesis in the kindling model.

  15. Effects of spaced learning in the water maze on development of dentate granule cells generated in adult mice.

    Science.gov (United States)

    Trinchero, Mariela F; Koehl, Muriel; Bechakra, Malik; Delage, Pauline; Charrier, Vanessa; Grosjean, Noelle; Ladeveze, Elodie; Schinder, Alejandro F; Abrous, D Nora

    2015-11-01

    New dentate granule cells (GCs) are generated in the hippocampus throughout life. These adult-born neurons are required for spatial learning in the Morris water maze (MWM). In rats, spatial learning shapes the network by regulating their number and dendritic development. Here, we explored whether such modulatory effects exist in mice. New GCs were tagged using thymidine analogs or a GFP-expressing retrovirus. Animals were exposed to a reference memory protocol for 10-14 days (spaced training) at different times after newborn cells labeling. Cell proliferation, cell survival, cell death, neuronal phenotype, and dendritic and spine development were examined using immunohistochemistry. Surprisingly, spatial learning did not modify any of the parameters under scrutiny including cell number and dendritic morphology. These results suggest that although new GCs are required in mice for spatial learning in the MWM, they are, at least for the developmental intervals analyzed here, refractory to behavioral stimuli generated in the course of learning in the MWM.

  16. Noradrenaline blocks potassium conductance in rat dentate granule cells in vitro.

    Science.gov (United States)

    Haas, H L; Rose, G M

    1987-07-22

    The actions of noradrenaline and the beta-adrenergic agonist, isoproterenol, were studied on the dentate gyrus in hippocampal slices from rats using extra- and intracellular recording. These agents facilitated field EPSPs (excitatory postsynaptic potentials) and population spikes evoked by perforant path stimulation. Intracellular recording revealed an attenuation of the long lasting afterhyperpolarization (AHP) and the accommodation of cell discharge in response to depolarizing current injection. It is suggested that beta-receptor activation blocks a calcium-dependent potassium current.

  17. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    Energy Technology Data Exchange (ETDEWEB)

    Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Nakagawa, Shin [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takamura, Naoki [Pharmaceutical Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Osaka (Japan); Kato, Akiko [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takebayashi, Minoru [Department of Psychiatry, National Hospital Organization Kure Medical Center, Kure (Japan); Hisaoka-Nakashima, Kazue [Department of Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima (Japan); Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2013-05-17

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

  18. Tricyclic antidepressant amitriptyline indirectly increases the proliferation of adult dentate gyrus-derived neural precursors: an involvement of astrocytes.

    Directory of Open Access Journals (Sweden)

    Shuken Boku

    Full Text Available Antidepressants increase the proliferation of neural precursors in adult dentate gyrus (DG, which is considered to be involved in the therapeutic action of antidepressants. However, the mechanism underlying it remains unclear. By using cultured adult rat DG-derived neural precursors (ADP, we have already shown that antidepressants have no direct effects on ADP. Therefore, antidepressants may increase the proliferation of neural precursors in adult DG via unknown indirect mechanism. We have also shown that amitriptyline (AMI, a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA. These suggest that AMI-induced factors in astrocytes may increase the proliferation of neural precursors in adult DG. To test this hypothesis, we examined the effects of AMI-induced factors and conditioned medium (CM from PCA treated with AMI on ADP proliferation. The effects of CM and factors on ADP proliferation were examined with BrdU immunocytochemistry. AMI had no effect on ADP proliferation, but AMI-treated CM increased it. The receptors of GDNF, BDNF and FGF2, but not VEGF, were expressed in ADP. FGF2 significantly increased ADP proliferation, but not BDNF and GDNF. In addition, both of a specific inhibitor of FGF receptors and anti-FGF2 antibody significantly counteracted the increasing effect of CM on ADP proliferation. In addition, FGF2 in brain is mainly derived from astrocytes that are key components of the neurogenic niches in adult DG. These suggest that AMI may increase ADP proliferation indirectly via PCA and that FGF2 may a potential candidate to mediate such an indirect effect of AMI on ADP proliferation via astrocytes.

  19. Tooth replacement related to number of natural teeth in a dentate adult population in Bulgaria: a cross-sectional study

    NARCIS (Netherlands)

    Damyanov, N.D.; Witter, D.J.; Bronkhorst, E.M.; Creugers, N.H.J.

    2013-01-01

    PURPOSE: This study aimed to explore the relationships among tooth replacement, number of present natural teeth, and sociodemographic and behavioral factors in an adult population in Bulgaria. MATERIALS AND METHODS: Quota sampling was used to recruit 2,531 dentate subjects aged 20 years and over fro

  20. Dental status and associated factors in a dentate adult population in bulgaria: a cross-sectional survey.

    NARCIS (Netherlands)

    Damyanov, N.D.; Witter, D.J.; Bronkhorst, E.M.; Creugers, N.H.J.

    2012-01-01

    This study aimed to determine variations in the dental status of a dentate adult population in terms of "decayed," "missing," and "filled" teeth in relation to several sociodemographic and behavioral factors. Quota sampling was used to draw 2531 subjects aged 20 years and over. Data were collected b

  1. Improvement of isolation,culture and identification of neural stem cells from adult SD rat Hippocampus den-tate gyrus%成年 SD 大鼠海马齿状回神经干细胞分离培养和鉴定的改良

    Institute of Scientific and Technical Information of China (English)

    孟磊; 周文科; 金保哲; 惠磊; 钟根深; 李武雄; 王仲伟; 黄立勇; 张新中

    2014-01-01

    Objective To improve method for isolating ,culturing and identifying neural stem cells (NSCs)derived from the hippocampus dentate gyrus in adult SD rat ,observe characteristics of growth ,multiplication and differentiation ,and prepare NSCs for subsequent experiments.Methods The whole hippocampus dentate gyrus was separated from adult SD rat. Primary cells were acquired by making use of mechanical blow. The neural cell pellet were passaged by accutase digestion method ,pro-liferation of NSCs could be determined by cck-8 method. Cultured and differentiated cells were identified with multiple immuno-fluorescence cytochemistry method. Results Primary neural stem cells could be efficiently obtained by mechanical blow ,ac-cutase digestive method was more conducive to the neural stem cells in the process of subculture ,the CCK-8 method was simple and efficient to determine the proliferation of neural stem cells ,multiple immunofluorescence innovatively dynamically displayed the differentiation process of neural stem cells after being induced.Conclusion The improved method is more simple and effi-cient in obtaining and culturing a large number of cells. The isolated and cultured cells are determined to be neural stem cells by multiple immunofluorescence.%目的:改良成年SD大鼠神经干细胞分离、培养及鉴定方法,观察神经干细胞的生长、增殖及分化特点,为后续实验提供细胞。方法从成年SD大鼠分离出完整海马齿状回,采用机械吹打法获得原代细胞,用accutase消化传代,利用cck-8法检测神经干细胞的增殖情况,利用多重免疫荧光细胞化学方法鉴定神经干细胞及其分化细胞。结果机械吹打法可高效获得原代神经干细胞,accutase消化传代更有利于神经干细胞的传代培养,cck-8法简单高效的测定了神经干细胞的增殖,多重免疫荧光创新性的动态展示了神经干细胞经诱导分化后的分化过程。结论改良

  2. Effect of chronic stress and mifepristone treatment on voltage-dependent Ca2+ currents in rat hippocampal dentate gyrus.

    NARCIS (Netherlands)

    van Gemert, N.G.; Joëls, M.

    2006-01-01

    Chronic unpredictable stress affects many properties in rat brain. In the dentate gyrus, among other things, increased mRNA expression of the Ca2+ channel alpha1C subunit has been found after 21 days of unpredictable stress in combination with acute corticosterone application (100 nM). In the presen

  3. Postischemic Anhedonia Associated with Neurodegenerative Changes in the Hippocampal Dentate Gyrus of Rats

    Directory of Open Access Journals (Sweden)

    Jiro Kasahara

    2016-01-01

    Full Text Available Poststroke depression is one of the major symptoms observed in the chronic stage of brain stroke such as cerebral ischemia. Its pathophysiological mechanisms, however, are not well understood. Using the transient right middle cerebral artery occlusion- (MCAO-, 90 min operated rats as an ischemia model in this study, we first observed that aggravation of anhedonia spontaneously occurred especially after 20 weeks of MCAO, and it was prevented by chronic antidepressants treatment (imipramine or fluvoxamine. The anhedonia specifically associated with loss of the granular neurons in the ipsilateral side of hippocampal dentate gyrus and was also prevented by an antidepressant imipramine. Immunohistochemical analysis showed increased apoptosis inside the granular cell layer prior to and associated with the neuronal loss, and imipramine seemed to recover the survival signal rather than suppressing the death signal to prevent neurons from apoptosis. Proliferation and development of the neural stem cells were increased transiently in the subgranular zone of both ipsi- and contralateral hippocampus within one week after MCAO and then decreased and almost ceased after 6 weeks of MCAO, while chronic imipramine treatment prevented them partially. Overall, our study suggests new insights for the mechanistic correlation between poststroke depression and the delayed neurodegenerative changes in the hippocampal dentate gyrus with effective use of antidepressants on them.

  4. Status epilepticus increases mature granule cells in the molecular layer of the dentate gyrus in rats

    Institute of Scientific and Technical Information of China (English)

    Zhaoliang Liang; Fei Gao; Fajun Wang; Xiaochen Wang; Xinyu Song; Kejing Liu; Ren-Zhi Zhan

    2013-01-01

    Enhanced neurogenesis in the dentate gyrus of the hippocampus following seizure activity, especially status epilepticus, is associated with ectopic residence and aberrant integration of newborn granule cells. Hilar ectopic granule cells may be detrimental to the stability of dentate circuitry by means of their electrophysiological properties and synaptic connectivity. We hypothesized that status epilepticus also increases ectopic granule cells in the molecular layer. Status epilepticus was induced in male Sprague-Dawley rats by intraperitoneal injection of pilocarpine. Immunostaining showed that many doublecortin-positive cells were present in the molecular layer and the hilus 7 days after the induction of status epilepticus. At least 10 weeks after status epilepticus, the estimated number of cells positive for both prospero homeobox protein 1 and neuron-specific nuclear protein in the hilus was significantly increased. A similar trend was also found in the molecular layer. These findings indicate that status epilepticus can increase the numbers of mature and ectopic newborn granule cells in the molecular layer.

  5. Effects of bone morphogenetic protein-4 on spatial memory and cholinergic expression in the dentate gyrus after fornix-fimbria transection in rats

    Institute of Scientific and Technical Information of China (English)

    Lei Liu; Yilong Xue; Jingkun Pan; Yazhuo Hu; Yuhong Gao; Yun Luo

    2008-01-01

    BACKGROUND: Previous experiments have confirmed bone morphogenetic proteins (BMPs) upregulate cholinergic expression in neurons isolated from the embryonic rat hippocampus and cerebral cortex. Therefore, BMPs could be useful for treating Alzheimer's disease and other neurodegenerative diseases. OBJECTIVE: BMP-4 was infused into the hippocampal dentate gyrus of fornix-fimbria transected rats to test the effects of BMP-4 on cholinergic expression in dentate gyrus neurons, and to observe changes in spatial memory behavior. DESIGN: A randomized controlled animal experiment. SETTING: Department of Neurosurgery and Laboratory for Cell Biology, Institute of Geriatrics, General Hospital of Chinese PLA.MATERIALS: Twenty-seven healthy adult male Sprague Dawley (SD) rats, weighing 250-300 g, were provided by the Laboratory Animal Center of the General Hospital of Chinese PLA. Reagents: BMP-4 (B-2680, Sigma Company) and choline acetyl transferase (ChAT) antibody (AB5042, Chemicon Company) were used in this study. Equipments: a rat stereotaxic instrument (type: SN-2N, Narushige Group, Japan) and Image-prog-plus image analysis software (Media Cybernetics company, USA) were used in this study. The protocol was carried out in accordance with ethical guidelines for the use and care of animals.METHODS: This experiment was performed in the Institute of Geriatrics, General Hospital of Chinese PLA between July 2004 and March 2005. Rats were randomly divided into 4 groups: Alzheimer's disease group (n = 7), normal control group (n = 5), BMP-4-Alzheimer's disease group (n = 8), and model group (n = 7). In the Alzheimer's disease group, the left hippocampal fornix-fimbria of rats was transected to mimic Alzheimer's disease symptoms. In the BMP-4-Alzheimer's disease group, 1 μL BMP-4 (10 mg/L) was perfused into the left dentate gyrus with a microinjector at 1 μL/min. In the model group, 1 μL saline was perfused into the same position by the same method. Twenty-eight days after injection

  6. Melatonin restores normal Bax and Bcl-2 protein expression in the subgranular zone of the dentate gyrus in pinealectomized rats

    Institute of Scientific and Technical Information of China (English)

    Shengchang Zhang; Shuang Zhao; Lu Bai; Mingming Guan; Jielin Mo; Ling Lan

    2011-01-01

    In this study, we sought to elucidate the effects of melatonin on learning and memory as well as apoptosis and expression of the Bax or Bcl-2 proteins in the subgranular zone of the dentate gyrus in pinealectomized rats. Using the Morris water maze and the olfactory memory tests, we found that the average escape latency in pinealectomized rats was clearly increased compared with sham-operated rats. Moreover, the average escape latency in the melatonin-treated and pinealectomized rats was longer than that in the sham-operated rats and shorter than that in the pinealectomized and untreated rats. Immunohistochemistry and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) showed that there were fewer Bax immunoreactive cells and TUNEL-positive (apoptotic) cells but more Bcl-2 immunoreactive cells in the melatonin-treated rats compared with the pinealectomized rats. The sham-operated rats showed numbers of these cells similar to the melatonin-treated rats. These experimental findings demonstrate that melatonin treatment may reduce abnormal apoptosis by promoting gene expression of Bax and suppressing gene expression of Bcl-2 in the subgranular zone of the dentate gyrus in pinealectomized rats. These effects appear to result in the inhibition of cellular apoptosis and the improvement of spatial learning and memory in pinealectomized rats.

  7. Neurogenesis in the dentate gyrus of the rat hippocampus enhanced by tickling stimulation with positive emotion.

    Science.gov (United States)

    Yamamuro, Takuya; Senzaki, Kouji; Iwamoto, Satomi; Nakagawa, Yoshimi; Hayashi, Takashi; Hori, Miyo; Sakamoto, Shigeko; Murakami, Kazuo; Shiga, Takashi; Urayama, Osamu

    2010-12-01

    Hippocampal neurogenesis is influenced by many factors. In this study, we examined the effect of tactile stimulation (tickling), which induced positive emotion, on neurogenesis in the dentate gyrus (DG) of the hippocampus. Four week-old rats were tickled for 5 min/day on 5 consecutive days and received 5-bromo-2'-deoxyuridine (BrdU) administration for 4 days from the second tickling day. Then they were allowed to survive for 18 h or 3 weeks after the end of BrdU treatment. Neurogenesis in the DG was compared between the tickled and untickled rats by using immunohistochemistry with anti-BrdU antibody. The result showed that the number of BrdU- and NeuN (neural cell marker)-double positive neurons on 18h as well as 3 weeks of the survival periods was significantly increased in the tickled group as compared with the untickled group. The expression of mRNA of brain-derived neurotrophic factor (BDNF) in the hippocampus of the tickled rats was not altered when compared with the control rats. In conclusion, tickling stimulation which induces positive emotion may affect the generation and survival of new neurons of the DG through the BDNF-independent pathway.

  8. Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult mouse dentate gyrus

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    Ohira, Koji

    2010-09-01

    Full Text Available Abstract New granule cells are continuously generated in the dentate gyrus of the adult hippocampus. During granule cell maturation, the mechanisms that differentiate new cells not only describe the degree of cell differentiation, but also crucially regulate the progression of cell differentiation. Here, we describe a gene, tryptophan 2,3-dioxygenase (TDO, whose expression distinguishes stem cells from more differentiated cells among the granule cells of the adult mouse dentate gyrus. The use of markers for proliferation, neural progenitors, and immature and mature granule cells indicated that TDO was expressed in mature cells and in some immature cells. In mice heterozygous for the alpha-isoform of calcium/calmodulin-dependent protein kinase II, in which dentate gyrus granule cells fail to mature normally, TDO immunoreactivity was substantially downregulated in the dentate gyrus granule cells. Moreover, a 5-bromo-2'-deoxyuridine labeling experiment revealed that new neurons began to express TDO between 2 and 4 wk after the neurons were generated, when the axons and dendrites of the granule cells developed and synaptogenesis occurred. These findings indicate that TDO might be required at a late-stage of granule cell development, such as during axonal and dendritic growth, synaptogenesis and its maturation.

  9. Ethanol extract ofOenanthe javanica increases cell proliferation and neuroblast differentiation in the adolescent rat dentate gyrus

    Institute of Scientific and Technical Information of China (English)

    Bai Hui Chen; Jae Chul Lee; Eun Joo Bae; Yun Lyul Lee; Jong Dai Kim; Moo-Ho Won; Il Jun Kang; Joon Ha Park; Jeong Hwi Cho; In Hye Kim; Bich Na Shin; Ji Hyeon Ahn; Seok Joon Hwang; Bing Chun Yan; Hyun Jin Tae

    2015-01-01

    Oenanthe javanica is an aquatic perennial herb that belongs to theOenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glu-tamate-induced neurotoxicity. However, few studies regarding effects ofOenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract ofOenanthe javanica on cell proliferation and neu-roblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 (an endogenous marker for cell proliferation) and doublecortin (a marker for neuroblast). Our results showed thatOenanthe javanica extract signiifcantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was signiifcantly increased in the dentate gyrus of theOe-nanthe javanica extract-treated group compared with the control group. However, we did not ifnd that vascular endothelial growth factor expression was increased in theOenanthe javanica extract-treated group compared with the control group. These results indicate thatOenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-de-rived neurotrophic factor immunoreactivity in the rat dentate gyrus.

  10. Ethanol extract of Oenanthe javanica increases cell proliferation and neuroblast differentiation in the adolescent rat dentate gyrus

    Directory of Open Access Journals (Sweden)

    Bai Hui Chen

    2015-01-01

    Full Text Available Oenanthe javanica is an aquatic perennial herb that belongs to the Oenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glutamate-induced neurotoxicity. However, few studies regarding effects of Oenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract of Oenanthe javanica on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 (an endogenous marker for cell proliferation and doublecortin (a marker for neuroblast. Our results showed that Oenanthe javanica extract significantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was significantly increased in the dentate gyrus of the Oenanthe javanica extract-treated group compared with the control group. However, we did not find that vascular endothelial growth factor expression was increased in the Oenanthe javanica extract-treated group compared with the control group. These results indicate that Oenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-derived neurotrophic factor immunoreactivity in the rat dentate gyrus.

  11. In vivo electrophysiological investigations into the role of histamine in the dentate gyrus of the rat.

    Science.gov (United States)

    Manahan-Vaughan, D; Reymann, K G; Brown, R E

    1998-06-01

    Drugs acting at the three known classes of histamine receptors were injected intracerebroventricularly into the rat. The effects of these drugs upon synaptic potentials recorded from the dentate gyrus of the freely-moving rat were determined. Population spikes and field excitatory postsynaptic potentials were recorded from the granule cell layer of the dentate gyrus following stimulation of the perforant path. Drugs, dissolved in 0.9% NaCl were applied into the lateral cerebral ventricle in a volume of 5 microl over a period of 6 min. The histamine H1 receptor antagonist mepyramine (0.4 or 0.8 microg) had no significant effect on population spikes or field excitatory postsynaptic potentials. In contrast the H2 receptor antagonist cimetidine (3.25, 6.5 or 13 microg) showed a biphasic effect. At the lower doses (3.25 or 6.5 microg) a small (15%) depression of the field excitatory postsynaptic potentials and population spikes was observed beginning about 1 h following the infusion. At the highest dose tested (13 microg) a marked increase of the population spike was observed beginning immediately following the infusion and lasting for 90 min. Application of the H3 receptor agonist R-alpha-methylhistamine (0.2 microg) depressed the field excitatory postsynaptic potentials (15% at 4 h post-injection) and even more strongly the population spike (50%). Surprisingly, at higher doses (0.4 and 0.8 microg) no effect was seen. The H3 receptor antagonist thioperamide (0.41 and 0.82 microg) did not cause an increase in synaptic potentials but rather at the highest dose a small depression occurred at later time points (2-4 h following the infusion). At the lower dose (0.41 microg) thioperamide blocked the effect of R-alpha-methylhistamine (0.2 microg). These results show that the histaminergic system modulates information flow through the dentate gyrus in a complex manner involving both histamine H2 and H1 receptors.

  12. Regrowing the adult brain: NF-κB controls functional circuit formation and tissue homeostasis in the dentate gyrus.

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    Yvonne Imielski

    Full Text Available Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-κB resulted in severe defects in the neurogenic region (dentate gyrus of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-κB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-κB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-κB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-κB to be a therapeutic target for treating cognitive and mood disorders.

  13. Functional Analysis of Neurovascular Adaptations to Exercise in the Dentate Gyrus of Young Adult Mice Associated With Cognitive Gain

    OpenAIRE

    Clark, Peter J.; Brzezinska, Weronika J.; Puchalski, Emily K.; Krone, David A.; Rhodes, Justin S.

    2009-01-01

    The discovery that aerobic exercise increases adult hippocampal neurogenesis and can enhance cognitive performance holds promise as a model for regenerative medicine. This study adds two new pieces of information to the rapidly growing field. First, we tested whether exercise increases vascular density in the granular layer of the dentate gyrus, whole hippocampus, and striatum in C57BL/6J mice known to display procognitive effects of exercise. Second, we determined the extent to which new neu...

  14. Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats.

    Science.gov (United States)

    Chen, Chong; Shen, Feng-Yan; Zhao, Xuan; Zhou, Tao; Xu, Dao-Jie; Wang, Zhi-Ru; Wang, Ying-Wei

    2015-01-01

    Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.

  15. Late maturation of adult-born neurons in the temporal dentate gyrus.

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    Jason S Snyder

    Full Text Available Hippocampal function varies along its septotemporal axis, with the septal (dorsal pole more frequently involved in spatial learning and memory and the temporal (ventral pole playing a greater role in emotional behaviors. One feature that varies across these subregions is adult neurogenesis. New neurons are more numerous in the septal hippocampus but are more active in the temporal hippocampus during water maze training. However, many other aspects of adult neurogenesis remain unexplored in the context of septal versus temporal subregions. In addition, the dentate gyrus contains another functionally important anatomical division along the transverse axis, with the suprapyramidal blade showing greater experience-related activity than the infrapyramidal blade. Here we ask whether new neurons differ in their rates of survival and maturation along the septotemporal and transverse axes. We found that neurogenesis is initially higher in the infrapyramidal than suprapyramidal blade, but these cells are less likely to survive, resulting in similar densities of neurons in the two blades by four weeks. Across the septotemporal axis, neurogenesis was higher in septal than temporal pole, while the survival rate of new neurons did not differ. Maturation was assessed by immunostaining for the neuronal marker, NeuN, which increases in expression level with maturation, and for the immediate-early gene, Arc, which suggests a neuron is capable of undergoing activity-dependent synaptic plasticity. Maturation occurred approximately 1-2 weeks earlier in the septal pole than in the temporal pole. This suggests that septal neurons may contribute to function sooner; however, the prolonged maturation of new temporal neurons may endow them with a longer window of plasticity during which their functions could be distinct from those of the mature granule cell population. These data point to subregional differences in new neuron maturation and suggest that changes in

  16. Neuronal apoptosis and synaptic density in the dentate gyrus of ischemic rats' response to chronic mild stress and the effects of Notch signaling.

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    Shaohua Wang

    Full Text Available Our previous research highlighted an inconsistency with Notch1 signaling-related compensatory neurogenesis after chronic mild stress (CMS in rodents suffering from cerebral ischemia, which continue to display post-stroke depressive symptoms. Here, we hypothesize that CMS aggrandized ischemia-related apoptosis injury and worsened synaptic integrity via gamma secretase-meditated Notch1 signaling. Adult rats were exposed to a CMS paradigm after left middle cerebral artery occlusion (MCAO. Open-field and sucrose consumption testing were employed to assess depression-like behavior. Gene expression of pro-apoptotic Bax, anti-apoptotic Bcl-2, and synaptic density-related synaptophysin were measured by western blotting and real-time PCR on Day 28 after MCAO surgery. CMS induced depressive behaviors in ischemic rats, which was accompanied by an elevation in Bax/bcl-2 ratio, TUNEL staining in neurons and reduced synaptophysin expression in the dentate gyrus. These collective effects were reversed by the gamma-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl]-S-phenyl-glycine t-butyl ester. We found that post-stroke stressors made neurons in the dentate gyrus vulnerable to apoptosis, which supports a putative role for Notch signaling in neural integrity, potentially in newborn cells' synaptic deficit with regard to preexisting cells. These findings suggest that post-stroke depression therapeutically benefits from blocking gamma secretase mediated Notch signaling, and whether this signaling pathway could be a therapeutic target needs to be further investigated.

  17. Estradiol and soy extract increase the production of new cells in the dentate gyrus of old rats.

    Science.gov (United States)

    Perez-Martin, Margarita; Salazar, Veronica; Castillo, Carmen; Ariznavarreta, Carmen; Azcoitia, Iñigo; Garcia-Segura, Luis M; Tresguerres, Jesus A F

    2005-05-01

    In young rodents, estradiol increases cell proliferation in the dentate gyrus of the hippocampus. However, it is unknown if the old brain retains this response to estradiol. Here we assessed the generation of new cells in the dentate gyrus of old rats after administration of estradiol or a soy extract, since soy is used as an alternative to hormonal replacement therapy in postmenopausal women. In a first experiment, 12-month-old animals were ovariectomized and studied at 14, 18 or 22 months of age. The production of new cells, assessed by the incorporation of bromodeoxyuridine (BrdU), was similar in 14- and 18-month-old rats. However, there was a significant reduction in the number of BrdU-immunoreactive cells at 22 months of age. In a second experiment, 22-month-old ovariectomized animals were treated for 10 weeks with a weekly s.c. injection of 150 microg estradiol valerianate or with 60 mg/kg per day soy extract added to the drinking water. Both treatments increased significantly the production of new cells in the dentate gyrus. These findings indicate that the brains of old rats retain the ability to increase the production of new cells in response to estradiol and soy extracts.

  18. Diffusion tensor MRI shows progressive changes in the hippocampus and dentate gyrus after status epilepticus in rat - histological validation with Fourier-based analysis.

    Science.gov (United States)

    Salo, Raimo A; Miettinen, Tuukka; Laitinen, Teemu; Gröhn, Olli; Sierra, Alejandra

    2017-03-04

    Imaging markers for monitoring disease progression, recovery, and treatment efficacy are a major unmet need for many neurological diseases, including epilepsy. Recent evidence suggests that diffusion tensor imaging (DTI) provides high microstructural contrast even outside major white matter tracts. We hypothesized that in vivo DTI could detect progressive microstructural changes in the dentate gyrus and the hippocampal CA3bc in the rat brain after status epilepticus (SE). To test this hypothesis, we induced SE with systemic kainic acid or pilocarpine in adult male Wistar rats and subsequently scanned them using in vivo DTI at five time-points: prior to SE, and 10, 20, 34, and 79 days post SE. In order to tie the DTI findings to changes in the tissue microstructure, myelin- and glial fibrillary acidic protein (GFAP)-stained sections from the same animals underwent Fourier analysis. We compared the Fourier analysis parameters, anisotropy index and angle of myelinated axons or astrocyte processes, to corresponding DTI parameters, fractional anisotropy (FA) and the orientation angle of the principal eigenvector. We found progressive detectable changes in DTI parameters in both the dentate gyrus (FA, axial diffusivity [D||], linear anisotropy [CL] and spherical anisotropy [CS], pmixed-effects model [LMEM]) and the CA3bc (FA, D||, CS, and angle, p<0.001, LMEM; CL and planar anisotropy [CP], p<0.01, LMEM) post SE. The Fourier analysis revealed that both myelinated axons and astrocyte processes played a role in the water diffusion anisotropy changes detected by DTI in individual portions of the dentate gyrus (suprapyramidal blade, mid-portion, and infrapyramidal blade). In the whole dentate gyrus, myelinated axons markedly contributed to the water diffusion changes. In CA3bc as well as in CA3b and CA3c, both myelinated axons and astrocyte processes contributed to water diffusion anisotropy and orientation. Our study revealed that DTI is a promising method for noninvasive

  19. Properties of doublecortin-(DCX)-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice.

    Science.gov (United States)

    Klempin, Friederike; Kronenberg, Golo; Cheung, Giselle; Kettenmann, Helmut; Kempermann, Gerd

    2011-01-01

    The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex) sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX) is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise), also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.

  20. Maternal Exposure to Valproic Acid Primarily Targets Interneurons Followed by Late Effects on Neurogenesis in the Hippocampal Dentate Gyrus in Rat Offspring.

    Science.gov (United States)

    Watanabe, Yousuke; Murakami, Tomoaki; Kawashima, Masashi; Hasegawa-Baba, Yasuko; Mizukami, Sayaka; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2017-01-01

    Valproic acid (VPA) is used to establish models of experimental autism. The present study investigated the developmental exposure effect of VPA on postnatal hippocampal neurogenesis in accordance with the exposure scheme of OECD Test Guideline 426 adopted for developmental neurotoxicity. Pregnant rats were administered drinking water containing 0, 667, or 2000 ppm VPA from gestational day 6 until day 21 post-delivery. In the subgranular zone (SGZ) and granule cell layer (GCL) of offspring, the number of granule cell lineage subpopulations remained unchanged upon weaning. However, in the hilus of the dentate gyrus, the number of reelin(+) interneurons decreased at ≥667 ppm, and the number of PVALB(+) or GAD67(+) interneurons decreased at 2000 ppm. Conversely, Reln and Gad1 transcript levels increased at 2000 ppm, but Pvalb and Grin2d decreased, in the dentate gyrus. At the adult stage, PCNA(+) proliferating SGZ cells, NeuN(+) postmitotic SGZ/GCL neurons, and ARC(+) or COX2(+) GCL neurons increased at ≥667 ppm. In the dentate hilus, decreases in GAD67(+) interneuron subpopulations and Grin2d transcript levels sustained at 2000 ppm. These results suggested that VPA primarily targets interneurons by developmental exposure, and this is followed by late effects on granule cell lineages, likely by influencing SGZ cell proliferation and synaptic plasticity. A reduced population of reelin(+) or PVALB(+) interneurons did not affect distribution of granule cell lineage subpopulations upon weaning. The late effect on neurogenesis, which resulted in increased GCL neurons, might be the result of a sustained decrease in GAD67(+) interneurons expressing NR2D encoded by Grin2d.

  1. Neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress in rats with streptozotocin-induced type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    Sang Gun Lee; In Koo Hwang; Seung Myung Moon; Dae Young Yoo; Hyo Young Jung; Sung Min Nam; Jong Whi Kim; Jung Hoon Choi; Sun Shin Yi; Moo-Ho Won; Yeo Sung Yoon

    2015-01-01

    In this study, we investigated the effects of streptozotocin-induced type 1 diabetes on antioxi-dant-like protein-1 immunoreactivity, protein carbonyl levels, and malondialdehyde formation, a marker for lipid peroxidation, in the hippocampus. For this study, streptozotocin (75 mg/kg) was intraperitoneally injected into adult rats to induce type 1 diabetes. The three experimental pa-rameters were determined at 2, 3, 4 weeks after streptozotocin treatment. Fasting blood glucose levels signiifcantly increased by 20.7–21.9 mM after streptozotocin treatment. The number of antioxidant-like protein-1 immunoreactive neurons signiifcantly decreased in the hippocampal CA1 region, but not the dentate gyrus, 3 weeks after streptozotocin treatment compared to the control group. Malondialdehyde and protein carbonyl levels, which are modiifed by oxidative stress, signiifcantly increased with a peak at 3 weeks after malondialdehyde treatment, and then decreased 4 weeks after malondialdehyde treatment. These results suggest that neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress 3 weeks after malondialdehyde treatment.

  2. Neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress in rats with streptozotocin-induced type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Sang Gun Lee

    2015-01-01

    Full Text Available In this study, we investigated the effects of streptozotocin-induced type 1 diabetes on antioxidant-like protein-1 immunoreactivity, protein carbonyl levels, and malondialdehyde formation, a marker for lipid peroxidation, in the hippocampus. For this study, streptozotocin (75 mg/kg was intraperitoneally injected into adult rats to induce type 1 diabetes. The three experimental parameters were determined at 2, 3, 4 weeks after streptozotocin treatment. Fasting blood glucose levels significantly increased by 20.7-21.9 mM after streptozotocin treatment. The number of antioxidant-like protein-1 immunoreactive neurons significantly decreased in the hippocampal CA1 region, but not the dentate gyrus, 3 weeks after streptozotocin treatment compared to the control group. Malondialdehyde and protein carbonyl levels, which are modified by oxidative stress, significantly increased with a peak at 3 weeks after malondialdehyde treatment, and then decreased 4 weeks after malondialdehyde treatment. These results suggest that neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress 3 weeks after malondialdehyde treatment.

  3. Activation of dentate hilar neurons by stimulation of the fimbria in rat hippocampal slices

    OpenAIRE

    SCHARFMAN, HELEN E.

    1993-01-01

    It is has been shown that the major afferent input to the dentate gyrus, the perforant path, excites dentate hilar neurons. However, little is known about the other inputs to hilar cells. Therefore, we examined the responses of hilar neurons to stimulation of the fimbria. We positioned our stimulating electrodes so that granule cells were not excited antidromically by fimbria stimulation, although action potentials were easily triggered in area CA3b and CA3c pyramidal cells by such stimulatio...

  4. Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats.

    Science.gov (United States)

    Kireev, R A; Vara, E; Tresguerres, J A F

    2013-08-01

    It has been suggested that the age-related decrease in the number of neurons in the hippocampus that leads to alterations in brain function, may be associated with an increase in apoptosis due to the reduced secretion of growth hormone (GH) and/or melatonin in old animals. In order to investigate this possibility, male Wistar rats of 22 months of age were divided into three groups. One group remained untreated and acted as the control group. The second was treated with growth hormone (hGH) for 10 weeks (2 mg/kg/d sc) and the third was subjected to melatonin treatment (1 mg/kg/d) in the drinking water for the same time. A group of 2-months-old male rats was used as young controls. All rats were killed by decapitation at more than 24 month of age and dentate gyri of the hippocampi were collected. Aging in the dentate gyrus was associated with an increase in apoptosis promoting markers (Bax, Bad and AIF) and with the reduction of some anti-apoptotic ones (XIAP, NIAP, Mcl-1). Expressions of sirtuin 1 and 2 (SIRT1 and 2) as well as levels of HSP 70 were decreased in the dentate gyrus of old rats. GH treatment was able to reduce the pro/anti-apoptotic ratio to levels observed in young animals and also to increase SIRT2. Melatonin reduced also expression of pro-apoptotic genes and proteins (Bax, Bad and AIF), and increased levels of myeloid cell leukemia-1 proteins and SIRT1. Both treatments were able to reduce apoptosis and to enhance survival markers in this part of the hippocampus.

  5. Properties of doublecortin-(DCX-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice.

    Directory of Open Access Journals (Sweden)

    Friederike Klempin

    Full Text Available The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise, also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.

  6. Strain-dependent variations in spatial learning and in hippocampal synaptic plasticity in the dentate gyrus of freely behaving rats

    Directory of Open Access Journals (Sweden)

    Denise eManahan-Vaughan

    2011-03-01

    Full Text Available Hippocampal synaptic plasticity is believed to comprise the cellular basis for spatial learning. Strain-dependent differences in synaptic plasticity in the CA1 region have been reported. However, it is not known whether these differences extend to other synapses within the trisynaptic circuit, although there is evidence for morphological variations within that path. We investigated whether Wistar and Hooded Lister (HL rat strains express differences in synaptic plasticity in the dentate gyrus in vivo. We also explored whether they exhibit differences in the ability to engage in spatial learning in an 8-arm radial maze. Basal synaptic transmission was stable over a 24h period in both rat strains, and the input-output relationship of both strains was not significantly different. Paired-pulse analysis revealed significantly less paired-pulse facilitation in the Hooded Lister strain when pulses were given 40-100 msec apart. Low frequency stimulation at 1Hz evoked long-term depression (>24h in Wistar and short-term depression (<2h in HL rats; 200Hz stimulation induced long-term potentiation (>24h in Wistar, and a transient, significantly smaller potentiation (<1h in HL rats, suggesting that HL rats have higher thresholds for expression of persistent synaptic plasticity. Training for 10d in an 8-arm radial maze revealed that HL rats master the working memory task faster than Wistar rats, although both strains show an equivalent performance by the end of the trial period. HL rats also perform more efficiently in a double working and reference memory task. On the other hand, Wistar rats show better reference memory performance on the final (8-10 days of training. Wistar rats were less active and more anxious than HL rats.These data suggest that strain-dependent variations in hippocampal synaptic plasticity occur in different hippocampal synapses. A clear correlation with differences in spatial learning is not evident however.

  7. Influence of superior cervical ganglionectomy on hippocampal neurogenesis and learning and memory in adult rats

    Institute of Scientific and Technical Information of China (English)

    Yanping Ding; Baoping Shao; Shiyuan Yu; Shanting Zhao; Jianlin Wang

    2009-01-01

    BACKGROUND: Studies have shown that neurogenesis in the dentate gyrus plays an important role in learning and memory. However, studies have not determined whether the superior cervical ganglion or the sympathetic nerve system influences hippocampal neurogenesis or learning and memory in adult rats. OBJECTIVE: To observe differences in dentate gyrus neurogenesis, as well as learning and memory, in adult rats following superior cervical ganglionectomy. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Immunohistochemistry Laboratory of the School of Life Sciences in Lanzhou University from July 2006 to July 2007.MATERIALS: Doublecortin polyclonal antibody was provided by Santa Cruz Biotechnology, USA;avidin-biotin-peroxidase complex was purchased from Zhongshan Goldenbride Biotechnology, China;Morris water maze was bought from Taimeng Technology, China. METHODS: A total of 20 adult, male, Wistar rats were randomly divided into surgery and control groups, with 10 rats in each group. In the surgery group, the bilateral superior cervical ganglions were transected. In the control group, the superior cervical ganglions were only exposed, but no ganglionectomy was performed. MAIN OUTCOME MEASURES: To examine distribution, morphology, and number of newborn neurons in the dentate gyrus using doublecortin immunohistochemistry at 36 days following surgical procedures. To examine ability of learning and memory in adult rats using the Morris water maze at 30 days following surgical procedures. RESULTS: Doublecortin immunohistochemical results showed that a reduction in the number of doublecortin-positive neurons in the surgery group compared to the control group (P<0.05), while the distribution of doublecortin-positive neurons was identical in the two groups. The surgery group exhibited significantly worse performance in learning and spatial memory tasks compared to the control group (P<0.05). CONCLUSION: Superior cervical ganglionectomy

  8. The dentate mossy fibers

    DEFF Research Database (Denmark)

    Blaabjerg, Morten; Zimmer, Jens

    2007-01-01

    Hippocampal mossy fibers are the axons of the dentate granule cells and project to hippocampal CA3 pyramidal cells and mossy cells of the dentate hilus (CA4) as well as a number of interneurons in the two areas. Besides their role in hippocampal function, studies of which are still evolving and t....... These features are the topic of this review, which will use the mossy fiber system of the rat as basis and reference in its aim to provide an up-to-date, yet historically based guide to students in the field...

  9. Melatonin and oestrogen treatments were able to improve neuroinflammation and apoptotic processes in dentate gyrus of old ovariectomized female rats.

    Science.gov (United States)

    Kireev, Roman A; Vara, Elena; Viña, Jose; Tresguerres, Jesus A F

    2014-01-01

    The aim of this study was to determine the outcomes of oestrogen and melatonin treatments following long-term ovarian hormone depletion on neuroinflammation and apoptotic processes in dentate gyrus of hippocampi. Forty-six female Wistar rats of 22 months of age were used. Twelve of them remained intact, and the other 34 were ovariectomized at 12 months of age. Ovariectomized animals were divided into three groups and treated for 10 weeks with oestrogens, melatonin or saline. All rats were killed by decapitation at 24 months of age, and dentate gyri were collected. A group of 2 month-old intact female rats was used as young control. The levels of pro-inflammatory cytokines and heat shock protein 70 (HSP 70) were analysed by ELISA. The expressions of TNFα, IL1β, GFAP, nNOS, iNOS, HO-1, NFκB, Bax, Bad, AIF, Bcl2 and SIRT1 genes were detected by real-time (RT)-PCR. Western blots were used to measure the protein expression of NFκB p65, NFκB p50/105, IκBα, IκBβ, p38 MAPK, MAP-2 and synapsin I. We have assessed the ability of 17β-oestradiol and melatonin administration to downregulate markers of neuroinflammation in the dentate gyrus of ovariectomized female rats. Results indicated that 17β-oestradiol and melatonin treatments were able to significantly decrease expression of pro-inflammatory cytokines, iNOS and HO-1 in the hippocampus when compared to non-treated animals. A similar age- and long-term ovarian hormone depletion- related increase in GFAP was also attenuated after both melatonin and oestradiol treatments. In a similar way to oestradiol, melatonin decreased the activation of p38 MAPK and NFκB pathways. The treatments enhanced the levels of synaptic molecules synapsin I and MAP-2 and have been shown to modulate the pro-antiapoptotic ratio favouring the second and to increase SIRT1 expression. These findings support the potential therapeutic role of melatonin and oestradiol as protective anti-inflammatory agents for the central nervous system

  10. A STEREOLOGICAL ANALYSIS OF THE EFFECT OF EARLY POSTNATAL ETHANOL EXPOSURE ON NEURONAL NUMBERS IN RAT DENTATE GYRUS

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    Takanori Miki

    2011-05-01

    Full Text Available Maternal ethanol ingestion during pregnancy can cause fetal alcohol syndrome (FAS in their offspring. Among the symptoms of FAS, damage to the central nervous system has emerged as one of the most serious problems. We have previously shown that a relatively high dose of ethanol exposure during early postnatal life can cause alterations in spatial learning ability. This ability is controlled, at least in part, by the hippocampal formation. The purpose of the present study was to determine whether exposure of rat pups to ethanol during early postnatal life had effects on the total number of the dentate gyrus neurons. Wistar rats were exposed to a relatively high daily dose of ethanol between postnatal days 10 to 15. Ethanol exposure was achieved by placing rat pups in a chamber containing ethanol vapour for 3 hours a day. The blood ethanol concentration was found to be about 430 mg/dL at the end of the exposure period. Groups of ethanol treated (ET, separation controls (SC and mother reared controls (MRC were anaesthetised and killed at 16-days-of-age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle was used to determine the volume of subdivisions of the dentate gyrus, and the physical disector method was used to estimate the numerical densities of neurons within each subdivision. The total number of neurons was calculated by multiplying estimates of the numerical density with the volume. There was, on average, about 421,000 granule cells in all three treatment groups. In the hilus region, ET rats had about 27,000 neuronal cells. This value was significantly smaller than the average of 38,000 such neurons estimated to be present in both MRC and SC animals. It is concluded that neurons in the hilus region of the dentate gyrus may be particularly vulnerable to the effects of a high dose of ethanol exposure during PND 10-15. It is likely that this deficit was due to neuronal death induced by some mechanisms related to

  11. Effect of low-frequency stimulation on kindling induced changes in rat dentate gyrus: an ultrastructural study.

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    Rohani, Razieh; Piryaei, Abbas; Jahanshahi, Ali; Sadeghi, Yousef; Mirnajafi-Zadeh, Javad

    2014-03-01

    It has been shown that low-frequency stimulation (LFS) can induce anticonvulsant effects. In this study, the effect of different LFS frequencies on kindling induced behavioral and ultrastructural changes was investigated. For induction of kindled seizures in rats, stimulating and recording electrodes were implanted in perforant path and dentate gyrus, respectively. Animals were stimulated in a rapid kindling manner. Different groups of animals received LFS at different frequencies (0.5, 1 and 5 Hz) following kindling stimulations and their effects on kindling rate were determined using behavioral and ultrastructural studies. Kindling stimulations were applied for 7 days. Then, the animals were sacrificed and their dentate gyrus was sampled for ultrastructural studies under electron microscopy. All three used LFS frequencies (0.5, 1 and 5 Hz) had a significant inhibitory effect on kindling rate and decreased afterdischarge duration and the number of stimulations to achieve stage 4 and 5 seizures significantly. In addition, application of LFS prevented the increase in the post-synaptic density and induction of concave synaptic vesicles following kindling. There was no significant change between anticonvulsant effects of LFS at different frequencies. Obtained results show that LFS application can prevent the neuronal hyperexcitability by preventing the ultrastructural changes during kindling and this may be one of the mechanisms of LFS anticonvulsant effects.

  12. Persistent Hyperactivity of Hippocampal Dentate Interneurons after a Silent Period in the Rat Pilocarpine Model of Epilepsy

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    Xiaochen eWang

    2016-04-01

    Full Text Available Profile of GABAergic interneuron activity after pilocarpine-induced status epilepticus (SE was examined in the rat hippocampal dentate gyrus by analyzing immediate early gene expression and recording spontaneous firing at near resting membrane potential.SE for exact 2 hours or more than 2 hours was induced in the male Sprague-Dawley rats by an intraperitoneal injection of pilocarpine. Expression of immediate early genes was examined at 1 hour, 1 week, 2 weeks or more than 10 weeks after SE. For animals to be examined at 1 hour after SE, SE lasted for exact 2 hours was terminated by an intraperitoneal injection of diazepam. Spontaneous firing at near the resting membrane potential was recorded in interneurons located along the border between the granule cell layer and the hilus more than 10 weeks after SE. Results showed that both c-fos and activity-regulated cytoskeleton associated protein (Arc in hilar GABAergic interneurons were up-regulated after SE in a biphasic manner; they were increased at 1 hour and more than 2 weeks, but not at 1 week after SE. Ten weeks after SE, nearly 60% of hilar GABAergic cells expressed c-fos. With the exception of calretinin (CR-positive cells, percentages of hilar neuronal nitric oxide synthase (nNOS-, neuropeptide Y (NPY-, parvalbumin (PV-, and somatostatin (SOM-positive cells with c-fos expression are significantly higher than those of controls more than 10 weeks after SE. Without the resting membrane potential to be more depolarizing and changed threshold potential level in SE-induced rats, cell-attached recording revealed that nearly 90% of hilar interneurons fired spontaneously at near the resting membrane potential while only 22% of the same cell population did so in the controls.In conclusion, pilocarpine-induced SE eventually leads to a state in which surviving dentate GABAergic interneurons become hyperactive with a subtype-dependent manner; this implies that a fragile balance between excitation and

  13. Effects of Imipramine and Lithium on the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in Adrenocorticotropic Hormone-treated Rats

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    Doi,Maho

    2010-08-01

    Full Text Available We examined the influence of chronic adrenocorticotropic hormone (ACTH treatment on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in rats. ACTH treatment for 14 days decreased the number of such cells. The administration of imipramine or lithium alone for 14 days had no effect in saline-treated rats. The effect of ACTH was blocked by the administration of imipramine. Furthermore, the coadministration of imipramine and lithium for 14 days significantly increased the number of Ki-67-positive cells in both the saline and ACTH-treated rats. The coadministration of imipramine and lithium normalized the cell proliferation in the dentate gyrus of the hippocampus in rats treated with ACTH.

  14. The contrasting effects of dendrotoxins and other potassium channel blockers in the CA1 and dentate gyrus regions of rat hippocampal slices

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    Southan, A P; Owen, D G

    1997-01-01

    The effects of potassium channel blocking compounds on synaptic transmission in the CA1 and dentate gyrus regions of the rat hippocampus were examined by means of simultaneous field potential recording techniques in brain slices.4-Aminopyridine (4-AP) enhanced the excitatory postsynaptic potential (e.p.s.p.) and induced multiple population spike responses in both regions. EC50 values were 6.7 μM in the CA1 (n=5) and 161.7 μM (n=5) in the dentate gyrus.Tetraethylammonium (TEA) increased the am...

  15. Functional analysis of neurovascular adaptations to exercise in the dentate gyrus of young adult mice associated with cognitive gain.

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    Clark, Peter J; Brzezinska, Weronika J; Puchalski, Emily K; Krone, David A; Rhodes, Justin S

    2009-10-01

    The discovery that aerobic exercise increases adult hippocampal neurogenesis and can enhance cognitive performance holds promise as a model for regenerative medicine. This study adds two new pieces of information to the rapidly growing field. First, we tested whether exercise increases vascular density in the granular layer of the dentate gyrus, whole hippocampus, and striatum in C57BL/6J mice known to display procognitive effects of exercise. Second, we determined the extent to which new neurons from exercise participate in the acute neuronal response to high levels of running in B6D2F1/J (F1 hybrid of C57BL/6J female by DBA/2J male). Mice were housed with or without a running wheel for 50 days (runner vs. sedentary). The first 10 days, they received daily injections of BrdU to label dividing cells. The last 10 days, mice were tested for performance on the Morris water maze and rotarod and then euthanized to measure neurogenesis, c-Fos induction from running and vascular density. In C57BL/6J, exercise increased neurogenesis, density of blood vessels in the dentate gyrus and striatum (but not whole hippocampus), and enhanced performance on the water maze and rotarod. In B6D2F1/J, exercise also increased hippocampal neurogenesis but not vascular density in the granular layer. Improvement on the water maze from exercise was marginal, and no gain was seen for rotarod, possibly because of a ceiling effect. Running increased the number of c-Fos positive neurons in the granular layer by fivefold, and level of running was strongly correlated with c-Fos within 90 min before euthanasia. In runners, approximately 3.3% (+/-0.008 S.E.) of BrdU-positive neurons in the middle of the granule layer displayed c-Fos when compared with 0.8% (+/-0.001) of BrdU-negative neurons. Results suggest that procognitive effects of exercise are associated with increased vascular density in the dentate gyrus and striatum in C57BL/6J mice, and that new neurons from exercise preferentially

  16. Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death

    Institute of Scientific and Technical Information of China (English)

    Bing Chun Yan; Yun Lyul Lee; Il-Jun Kang; Moo-Ho Won; Joon Ha Park; Bai Hui Chen; Jeong-Hwi Cho; In Hye Kim; Ji Hyeon Ahn; Jae-Chul Lee; In Koo Hwang; Jun Hwi Cho

    2014-01-01

    Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperito-neal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN;a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reac hed the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-im-munoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2′-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These ifndings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death.

  17. Effect of topiramate on partial excitatory amino acids in hippocampal dentate gyrus of rats after alcohol withdrawal

    Institute of Scientific and Technical Information of China (English)

    Qinghua Yang; Guang Wu; Haiying Jiang; Yuanzhe Jin; Songbiao Cui

    2006-01-01

    BACKGROUND: Many researches have indicated that the imbalances of various amino acid transmitters and neurotransmitters in brain are involved in the formation of alcohol withdrawal, especially that glutamic acid is one of the important transmitters for alcohol tolerance in central nervous system.OBJECTIVE: To observe the changes of excitatory amino acids in hippocampal dentate gyrus in rats with long-term alcohol drinking after withdrawal under consciousness, and investigate the therapeutic effect of topiramate on alcohol withdrawal.DESIGN: A randomized control animal experiment.SETTING: Department of Neurology, Affiliated Hospital of Yanbian University.MATERIALS: Thirty male Wistar rats of 4 months old, weighing 300-350 g, were purchased from the Experimental Animal Department, Medical College of Yanbian University. Topiramate was produced by Swish Cilag Company, and the batch number was 02CS063.METHODS: The experiments were carried out in the Department of Physiology, Medical College of Yanbian University from August 2005 to February 2006. ① The rats were divided randomly into three groups: control group (n=10), alcohol group (n=10) and topiramate-treated group (n=10). Rats in the alcohol group and topiramate-treated group were given intragastric perfusion of 500 g/L alcohol (10 mL/kg), once a day for 4 weeks successively, and then those in the topiramate-treated group were treated with 80 mg/kg topiramate at 24 hours after the last perfusion of alcohol, once a day for 3 days successively. Rats in the control group were intragastricly given isovolume saline. ② The withdrawal symptoms were assessed at 6, 30, 48 and 72 hours after the last perfusion of alcohol by using the withdrawal rating scale set by Erden et al,which had four observational indexes of stereotyped behaviors, agitation, tail stiffness and abnormal posture,each index was scored by 5 points, the higher the score, the more obvious the symptoms. ③ The contents of aspartic acid and glutamic acid

  18. Potential implications of a monosynaptic pathway from mossy cells to adult-born granule cells of the dentate gyrus.

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    Helen eScharfman

    2015-08-01

    Full Text Available The dentate gyrus (DG is important to many aspects of hippocampal function, but there are many aspects of the DG that are incompletely understood. One example is the role of mossy cells (MCs, a major DG cell type that is glutamatergic and innervates the primary output cells of the DG, the granule cells (GCs. MCs innervate the GCs as well as local circuit neurons that make GABAergic synapses on GCs, so the net effect of MCs on GCs - and therefore the output of the DG - is unclear.Here we first review fundamental information about MCs and the current hypotheses for their role in the normal DG and in diseases that involve the DG. Then we review previously published data which suggest that MCs are a source of input to a subset of GCs that are born in adulthood (adult-born GCs. In addition, we discuss the evidence that adult-born GCs may support the normal inhibitory 'gate' functions of the DG, where the GCs are a filter or gate for information from the entorhinal cortical input to area CA3. The implications are then discussed in the context of seizures and temporal lobe epilepsy (TLE. In TLE, it has been suggested that the DG inhibitory gate is weak or broken and MC loss leads to insufficient activation of inhibitory neurons, causing hyperexcitability. That idea was called the dormant basket cell hypothesis. Recent data suggest that loss of normal adult-born GCs may also cause disinhibition, and seizure susceptibility. Therefore, we propose a reconsideration of the dormant basket cell hypothesis with an intervening adult-born GC between the MC and basket cell and call this hypothesis the dormant immature granule cell hypothesis.

  19. BDNF Depresses Excitability of Parvalbumin-Positive Interneurons through an M-Like Current in Rat Dentate Gyrus.

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    Jose Luis Nieto-Gonzalez

    Full Text Available In addition to their classical roles in neuronal growth, survival and differentiation, neurotrophins are also rapid regulators of excitability, synaptic transmission and activity-dependent synaptic plasticity. We have recently shown that mature BDNF (Brain Derived Neurotrophic Factor, but not proBDNF, modulates the excitability of interneurons in dentate gyrus within minutes. Here, we used brain slice patch-clamp recordings to study the mechanisms through which BDNF modulates the firing of interneurons in rat dentate gyrus by binding to TrkB receptors. Bath application of BDNF (15 ng/ml under current-clamp decreased the firing frequency (by 80% and input resistance, blocking the delayed firing observed at near-threshold voltage ranges, with no changes in resting membrane potential or action potential waveform. Using TEA (tetraethylammonium, or XE991(a Kv7/KCNQ channel antagonist, the effect of BDNF was abolished, whereas application of retigabine (a Kv7/KCNQ channel opener mimicked the effect of BDNF, suggesting that the M-current could be implicated in the modulation of the firing. In voltage-clamp experiments, BDNF increased the M-like current amplitude with no change in holding current. This effect was again blocked by XE991 and mimicked by retigabine, the latter accompanied with a change in holding current. In agreement with the electrophysiology, parvalbumin-positive interneurons co-expressed TrkB receptors and Kv7.2/KCNQ2 channels. In conclusion, BDNF depresses the excitability of interneurons by activating an M-like current and possibly blocking Kv1 channels, thereby controlling interneuron resting membrane potential and excitability.

  20. BDNF Depresses Excitability of Parvalbumin-Positive Interneurons through an M-Like Current in Rat Dentate Gyrus.

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    Nieto-Gonzalez, Jose Luis; Jensen, Kimmo

    2013-01-01

    In addition to their classical roles in neuronal growth, survival and differentiation, neurotrophins are also rapid regulators of excitability, synaptic transmission and activity-dependent synaptic plasticity. We have recently shown that mature BDNF (Brain Derived Neurotrophic Factor), but not proBDNF, modulates the excitability of interneurons in dentate gyrus within minutes. Here, we used brain slice patch-clamp recordings to study the mechanisms through which BDNF modulates the firing of interneurons in rat dentate gyrus by binding to TrkB receptors. Bath application of BDNF (15 ng/ml) under current-clamp decreased the firing frequency (by 80%) and input resistance, blocking the delayed firing observed at near-threshold voltage ranges, with no changes in resting membrane potential or action potential waveform. Using TEA (tetraethylammonium), or XE991(a Kv7/KCNQ channel antagonist), the effect of BDNF was abolished, whereas application of retigabine (a Kv7/KCNQ channel opener) mimicked the effect of BDNF, suggesting that the M-current could be implicated in the modulation of the firing. In voltage-clamp experiments, BDNF increased the M-like current amplitude with no change in holding current. This effect was again blocked by XE991 and mimicked by retigabine, the latter accompanied with a change in holding current. In agreement with the electrophysiology, parvalbumin-positive interneurons co-expressed TrkB receptors and Kv7.2/KCNQ2 channels. In conclusion, BDNF depresses the excitability of interneurons by activating an M-like current and possibly blocking Kv1 channels, thereby controlling interneuron resting membrane potential and excitability.

  1. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease.

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    José J Rodríguez

    Full Text Available It has become generally accepted that new neurones are added and integrated mainly in two areas of the mammalian CNS, the subventricular zone and the subgranular zone (SGZ of the dentate gyrus (DG of the hippocampus, which is of central importance in learning and memory. The newly generated cells display neuronal morphology, are able to generate action potentials and receive functional synaptic inputs, i.e. their properties are similar to those found in mature neurones. Alzheimer's disease (AD is the primary and widespread cause of dementia and is an age-related, progressive and irreversible neurodegenerative disease that deteriorates cognitive functions. Here, we have used male and female triple transgenic mice (3xTg-AD harbouring three mutant genes (beta-amyloid precursor protein, presenilin-1 and tau and their respective non-transgenic (non-Tg controls at 2, 3, 4, 6, 9 and 12 months of age to establish the link between AD and neurogenesis. Using immunohistochemistry we determined the area density of proliferating cells within the SGZ of the DG, measured by the presence of phosphorylated Histone H3 (HH3, and their possible co-localisation with GFAP to exclude a glial phenotype. Less than 1% of the HH3 labeled cells co-localised with GFAP. Both non-Tg and 3xTg-AD showed an age-dependent decrease in neurogenesis. However, male 3xTg-AD mice demonstrated a further reduction in the production of new neurones from 9 months of age (73% decrease and a complete depletion at 12 months, when compared to controls. In addition, female 3xTg-AD mice showed an earlier but equivalent decrease in neurogenesis at 4 months (reduction of 63% with an almost inexistent rate at 12 months (88% decrease compared to controls. This reduction in neurogenesis was directly associated with the presence of beta-amyloid plaques and an increase in the number of beta-amyloid containing neurones in the hippocampus; which in the case of 3xgTg females was directly correlated. These

  2. Effects of amitriptyline and fluoxetine on synaptic plasticity in the dentate gyrus of hippocampal formation in rats

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    Ghasem Zarei

    2014-01-01

    Full Text Available Background: Several studies have been shown that antidepressant drugs have contradictory effects on cognitive processes. Therefore, the aim of this study was to investigate the effects of amitriptyline and fluoxetine on synaptic plasticity in the dentate gyrus (DG of the hippocampal formation in rat. Materials and Methods: Experimental groups were the control, the fluoxetine, and amitriptyline. The rats were treated for 21 days and then, paired pulse facilitation/inhibition (PPF/I and long-term potentiation (LTP in perforant path-DG synapses were assessed (by 400 Hz tetanization. Field excitatory post-synaptic potential (fEPSP slope and population spike (PS amplitude were measured. Results: The results of PPF/I showed that PS amplitude ratios were increased in 10-70 ms inter-stimulus intervals in the amitriptyline group compared to the control group. In the fluoxetine group, EPSP slope ratios were decreased in intervals 30, 40, and 50 ms inter-stimulus intervals compared to the control group. The PS-LTP was significantly lower in the fluoxetine and the amitriptyline groups with respect to the control group. Conclusion: The results showed that fluoxetine and amitriptyline affect synaptic plasticity in the hippocampus and these effects is probably due to the impact on the number of active neurons.

  3. Replacement of asymmetric synaptic profiles in the molecular layer of dentate gyrus following cycloheximide in the pilocarpine model in rats.

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    Simone eBittencourt

    2015-11-01

    Full Text Available Mossy fiber sprouting is among the best-studied forms of post-lesional synaptic plasticity and is regarded by many as contributory to seizures in both humans and animal models of epilepsy. It is not known whether mossy fiber sprouting increases the number of synapses in the molecular layer or merely replaces lost contacts. Using the pilocarpine model of status epilepticus to induce mossy fiber sprouting, and cycloheximide to block this sprouting, we evaluated at the ultrastructural level the number and type of asymmetric synaptic contacts in the molecular layer of the dentate gyrus. As expected, whereas pilocarpine-treated rats had dense silver grain deposits in the inner molecular layer (reflecting mossy fiber sprouting, pilocarpine+cycloheximide-treated animals did not differ from controls. Both groups of treated rats (Pilo group and CHX+Pilo group had reduced density of asymmetric synaptic profiles (putative excitatory synaptic contacts, which was greater for cycloheximide-treated animals. For both treated groups the loss of excitatory synaptic contacts was even greater in the outer molecular layer than in the best studied inner molecular layer (in which mossy fiber sprouting occurs. These results indicate that mossy fiber sprouting tends to replace lost synaptic contacts rather than increase the absolute number of contacts. We speculate that the overall result is more consistent with restored rather than with increased excitability.

  4. Temporal and spacial relationships between PSA-NCAM-expressing, newly generated granule cells, and radial glia-like cells in the adult dentate gyrus.

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    Seki, T; Arai, Y

    1999-08-02

    The granule cell layer of the adult dentate gyrus possesses two characteristics of an immature nervous system. The first is that granule cells continue to be generated in the innermost region of the granule cell layer, and newly generated and developing granule cells in the adult express highly polysialylated neural cell adhesion molecule (PSA-NCAM). PSA-NCAM-expressing apical dendrites have dynamically unstable processes such as irregular shafts and many stick-like or fan-shaped fine processes. The second is that radial glia-like cells expressing glial fibrillary acidic protein (GFAP) remain in a similar region of the granular layer. The numbers of PSA-NCAM-expressing granule cells and GFAP-expressing radial glia-like cells show a parallel age-dependent decrease during aging. Moreover, by using confocal laser scanning microscopy and immunoelectron microscopy, we demonstrated that PSA-NCAM-expressing dendrites and GFAP-expressing radial processes are partly in contact with each other, and occasionally the radial glial processes envelop the PSA-NCAM-positive dendritic processes. The temporal and spatial relationship between the two immature elements suggests that the processes of the radial glia-like cells are closely associated with the dendritic growth of the newly generated granule cells in the adult dentate gyrus and that these two immature features of neurons and glia in the dentate gyrus diminish with age.

  5. Evaluation of the protective effects of tocotrienol-rich fraction from palm oil on the dentate gyrus following chronic restraint stress in rats

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    Saiful Bhari Talip

    2013-06-01

    Full Text Available Exposure to chronic restraint stress has been shown to cause a number of morphological changes in the hippocampal formation of rats. Tocotrienol, an isoform of vitamin E, exhibits numerous health benefits, different from those of tocopherol. Recent studies have demonstrated that tocotrienol prevents stress-induced changes in the gastric mucosa, thus indicating that it may also protect other organs such as the brain from the damaging effects of stress. Therefore, the aim of the present study was to investigate the protective effect of tocotrienol-rich fraction (TRF extracted from palm oil on the dentate gyrus of rats following exposure to chronic restraint stress. Thirty-six male Sprague Dawley rats were divided into four groups: control, stress, tocotrienol and combination of stress and tocotrienol. Animals were stressed by restraining them for 5 hours every day for 21 consecutive days. TRF was administered via oral gavage at a dose of 200 mg/kg body weight. Our results showed that the plasma corticosterone level was significantly increased in response to stress, compared to the control. The results confirmed previous findings that chronic restraint stress suppresses cellular proliferation and reduces granule cell number in the dentate gyrus. However, TRF supplementation failed to prevent or minimize these stress-induced changes. Therefore, we conclude that TRF at the current dosage is not effective in preventing the morphological changes in the dentate gyrus induced by chronic restraint stress.

  6. Fluorescent labeling of newborn dentate granule cells in GAD67-GFP transgenic mice: a genetic tool for the study of adult neurogenesis.

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    Shengli Zhao

    Full Text Available Neurogenesis in the adult hippocampus is an important form of structural plasticity in the brain. Here we report a line of BAC transgenic mice (GAD67-GFP mice that selectively and transitorily express GFP in newborn dentate granule cells of the adult hippocampus. These GFP(+ cells show a high degree of colocalization with BrdU-labeled nuclei one week after BrdU injection and express the newborn neuron marker doublecortin and PSA-NCAM. Compared to mature dentate granule cells, these newborn neurons show immature morphological features: dendritic beading, fewer dendritic branches and spines. These GFP(+ newborn neurons also show immature electrophysiological properties: higher input resistance, more depolarized resting membrane potentials, small and non-typical action potentials. The bright labeling of newborn neurons with GFP makes it possible to visualize the details of dendrites, which reach the outer edge of the molecular layer, and their axon (mossy fiber terminals, which project to the CA3 region where they form synaptic boutons. GFP expression covers the whole developmental stage of newborn neurons, beginning within the first week of cell division and disappearing as newborn neurons mature, about 4 weeks postmitotic. Thus, the GAD67-GFP transgenic mice provide a useful genetic tool for studying the development and regulation of newborn dentate granule cells.

  7. Commissurally projecting inhibitory interneurons of the rat hippocampal dentate gyrus: a colocalization study of neuronal markers and the retrograde tracer Fluoro-gold.

    Science.gov (United States)

    Zappone, C A; Sloviter, R S

    2001-12-24

    Improved methods for detecting neuronal markers and the retrograde tracer Fluoro-Gold (FG) were used to identify commissurally projecting neurons of the rat hippocampus. In addition to the dentate hilar mossy cells and CA3 pyramidal cells shown previously to transport retrograde tracers after injection into the dorsal hippocampus, FG-positive interneurons of the dentate granule cell layer and hilus were detected in numbers greater than previously reported. FG labeling of interneurons was variable among animals, but was as high as 96% of hilar somatostatin-positive interneurons, 84% of parvalbumin-positive cells of the granule cell layer and hilus combined, and 33% of hilar calretinin-positive cells. By comparison, interneurons of the dentate molecular layer and all hippocampal subregions were conspicuously FG-negative. Whereas hilar mossy cells and CA3 pyramidal cells were FG-labeled throughout the longitudinal axis, FG-positive interneurons exhibited a relatively homotopic distribution. "Control" injections of FG into the neocortex, septum, and ventral hippocampus demonstrated that the homotopic labeling of dentate interneurons was injection site-specific, and that the CA1-CA3 interneurons unlabeled by contralateral hippocampal FG injection were nonetheless able to transport FG from the septum. These data suggest a hippocampal organizing principle according to which virtually all commissurally projecting hippocampal neurons share the property of being monosynaptic targets of dentate granule cells. Because granule cells innervate their exclusively ipsilateral target cells in a highly lamellar pattern, these results suggest that focal granule cell excitation may result in commissural inhibition of the corresponding "twin" granule cell lamella, thereby lateralizing and amplifying the influence of the initiating discharge.

  8. Despite strong behavioral disruption, Delta9-tetrahydrocannabinol does not affect cell proliferation in the adult mouse dentate gyrus.

    Science.gov (United States)

    Kochman, Linda J; dos Santos, Angela Amancio; Fornal, Casimir A; Jacobs, Barry L

    2006-10-01

    Marijuana is a widely abused illicit drug known to cause significant cognitive impairments. Marijuana has been hypothesized to target neurons in the hippocampus because of the abundance of cannabinoid receptors present in this structure. While there is no clear evidence of neuropathology in vivo, suppression of brain mitogenesis, and ultimately neurogenesis, may provide a sensitive index of marijuana's more subtle effects on neural mechanisms subserving cognitive functions. We examined the effects of different doses and treatment regimens of Delta(9)-tetrahydrocannabinol (THC), the main active ingredient in marijuana, on cell proliferation in the dentate gyrus of adult male mice. Following drug treatment, the thymidine analog 5-bromo-2'-deoxyuridine (BrdU; 200 mg/kg, i.p.) was administered two hours prior to sacrifice to assess cell proliferation, the first step in neurogenesis. Administration of THC produced dose-dependent catalepsy and suppression of motor activity. The number of BrdU-labeled cells was not significantly changed from vehicle control levels following either acute (1, 3, 10, 30 mg/kg, i.p.), sequential (two injections of 10 or 30 mg/kg, i.p., separated by 5 h), or chronic escalating (20 to 80 mg/kg, p.o.; for 3 weeks) drug administration. Furthermore, acute administration of the potent synthetic cannabinoid receptor agonist R-(+)-WIN 55,212-2 (WIN; 5 mg/kg, i.p.) also had no significant effect on cell proliferation. These findings provide no evidence for an effect of THC on hippocampal cell proliferation, even at doses producing gross behavioral intoxication. Whether marijuana or THC affects neurogenesis remains to be explored.

  9. The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats.

    Science.gov (United States)

    Walling, Susan G; Milway, J Stephen; Ingram, Matthew; Lau, Catherine; Morrison, Gillian; Martin, Gerard M

    2016-02-01

    Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200 Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30-32 days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25-30 days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60 days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this

  10. Electrophysiology and immunohistochemistry in the hippocampal ca1 and the dentate gyrus of rats chronically exposed to 1-bromopropane, a substitute for specific chlorofluorocarbons.

    Science.gov (United States)

    Fueta, Y; Fukuda, T; Ishidao, T; Hori, H

    2004-01-01

    1-Bromopropane is a newly introduced substitute for specific chlorofluorocarbons whose production was prohibited because of depletion of ozone layers. In this study, we analyzed disinhibitory effects induced by repetitive inhalation of 1-bromopropane for 12 weeks in the hippocampal CA1 and the dentate gyrus. In addition, reversal of the disinhibitory effects was examined 4 weeks after 1-bromopropane inhalation ceased. Exposure rats were placed in a stainless steel inhalation chamber at a concentration of 700 ppm, while the control group was provided only room air in the same type of chamber. Paired-pulse inhibition of population spike was considerably decreased (P1-Bromopropane-induced disinhibition was further analyzed by immunohistochemical methods. There were no apparent morphological defects in either excitatory or inhibitory neuronal components, supporting the reversibility of physiological changes. In conclusion, chronic inhalation of 1-bromopropane induces a disinhibition in the CA1 and dentate gyrus that is reversible following cessation of exposure.

  11. Actions of brain-derived neurotrophic factor in slices from rats with spontaneous seizures and mossy fiber sprouting in the dentate gyrus.

    Science.gov (United States)

    Scharfman, H E; Goodman, J H; Sollas, A L

    1999-07-01

    This study examined the acute actions of brain-derived neurotrophic factor (BDNF) in the rat dentate gyrus after seizures, because previous studies have shown that BDNF has acute effects on dentate granule cell synaptic transmission, and other studies have demonstrated that BDNF expression increases in granule cells after seizures. Pilocarpine-treated rats were studied because they not only have seizures and increased BDNF expression in granule cells, but they also have reorganization of granule cell "mossy fiber" axons. This reorganization, referred to as "sprouting," involves collaterals that grow into novel areas, i.e., the inner molecular layer, where granule cell and interneuron dendrites are located. Thus, this animal model allowed us to address the effects of BDNF in the dentate gyrus after seizures, as well as the actions of BDNF on mossy fiber transmission after reorganization. In slices with sprouting, BDNF bath application enhanced responses recorded in the inner molecular layer to mossy fiber stimulation. Spontaneous bursts of granule cells occurred, and these were apparently generated at the site of the sprouted axon plexus. These effects were not accompanied by major changes in perforant path-evoked responses or paired-pulse inhibition, occurred only after prolonged (30-60 min) exposure to BDNF, and were blocked by K252a. The results suggest a preferential action of BDNF at mossy fiber synapses, even after substantial changes in the dentate gyrus network. Moreover, the results suggest that activation of trkB receptors could contribute to the hyperexcitability observed in animals with sprouting. Because human granule cells also express increased BDNF mRNA after seizures, and sprouting can occur in temporal lobe epileptics, the results may have implications for understanding temporal lobe epilepsy.

  12. Differences in paired-pulse inhibition and facilitation in the dentate gyrus and CA3 field between dorsal and ventral rat hippocampus.

    Science.gov (United States)

    Pofantis, Hermes; Georgopoulos, Panagiotis; Petrides, Theodoros; Papatheodoropoulos, Costas

    2015-05-22

    We studied the processes of inhibition and facilitation in the dentate gyrus (DG) and the CA3 field by examining the effects of paired-pulse stimulation on the evoked population spike (PS) in dorsal (DH) and ventral (VH) hippocampal slices from the adult rat. The antidromic-orthodromic (A-O) and the orthodromic-orthodromic (O-O) paired-pulse stimulation protocols were used at varying inter-pulse intervals (IPI). In the DG, the A-O stimulation produced an early depression of PS lasting 30-40ms which was significantly stronger in the VH compared with DH. The O-O stimulation produced a biphasic pattern of effects, in both dorsal and ventral DG, consisting of an early depression of PS followed by facilitation at relatively longer intervals. In the DH but not the VH the phase of facilitation was followed by a late depression of PS (>200ms). In the CA3 field both A-O and O-O stimulation had a biphasic effect consisting of an early phase of strong depression of similar strength in DH and VH. The depression was followed by a phase of facilitation which was more pronounced with O-O stimulation. The facilitation observed with the O-O stimulation was much stronger in DH than VH and in DH only it was significantly reduced by the antagonist of GABAB receptors CGP52432. Furthermore, the facilitation was insensitive to changes in [Ca(2+)]o in both hippocampal poles. These findings suggest that the dorsal compared with ventral DG is more amenable to fast-frequency input but filters out slow-frequency inputs more reliably while the gating and amplification of the excitatory input in the CA3 circuitry is more prominent in DH than in VH.

  13. In Vivo Targeting of Adult Neural Stem Cells in the Dentate Gyrus by a Split-Cre Approach

    Directory of Open Access Journals (Sweden)

    Ruth Beckervordersandforth

    2014-02-01

    Full Text Available We describe the labeling of adult neural stem cells (aNSCs in the mouse and human dentate gyrus (DG by the combinatorial expression of glial fibrillary acidic protein (GFAP and Prominin1, as revealed by immunohistochemistry. Split-Cre-based genetic fate mapping of these double-positive cells in the adult murine DG reveals their NSC identity, as they are self-renewing and contribute to neurogenesis over several months. Their progeny reacts to stimuli such as voluntary exercise with increased neurogenesis. Prominin1+/GFAP+ cells also exist in the adult human DG, the only region in the human brain for which adult neurogenesis has been consistently reported. Our data, together with previous evidence of such double-positive NSCs in the developing murine brain and in neurogenic regions of vertebrates with widespread neurogenesis, suggest that Prominin1- and GFAP-expressing cells are NSCs in a wide range of species in development and adulthood.

  14. Effect of electroacupuncture on synaptic transmission in dentate gyrus of the hippocampus in cerebral ischemic injured rats

    Institute of Scientific and Technical Information of China (English)

    Haibo Yu; Zhuoxin Yang; Ling Wang; Min Pi; Jiawei Zhang

    2006-01-01

    BACKGROUND: Some studies suggest that the long-term potentiation (LTP) of synaptic transmission may be the basis for the neural synaptic plasticity of hippocampus, but can be evoked by various factors including electroacupuncture.OBJECTIVE: To observe the effect of electroacupuncture on the activities of basic synaptic transmission in dentate gyrus of hippocampus and the changes of high frequency stimulation (HFS) induced activity of synaptic transmission in cerebral ischemic injured rats.DESIGN: A randomized control trial.SETTING: Shenzhen Hospital of Traditional Chinese Medicine affiliated to Guangzhou University of Traditional Chinese Medicine.MATERIALS: Sixty healthy male Wistar rats, weighing 150-250 g, were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. The experiment began after adaptation of environment for 1 week under standard experimental environment. The main experimental instruments included the programming electrical acupuncture apparatus (PCEA, product of the Institute of Acupuncture and Meridians, Anhui College of Traditional Chinese Medicine) and multichannel physiologic recorder (RM-86, Nihon Konden).METHODS: The experiment was carried out in Guangzhou University of Traditional Chinese Medicine between July 2003 and July 2004. ① Embedding of brain electrodes: In reference of the Pellegrino's rat brain atlas, the bipolar electrode stimulator was embedded into the perforant path (PP) anterior to the entorhinal area with location coordinates of AP 7.5 mm, L 4.2 mm and H 3.0 mm, that is, 7.5 mm posterior to the anterior fontanelle, 4.2 mm laterally on the right side and 3.0 mm under the subcortex. The subcortex recorder electrode coordinates are AP 3.8 mm, L 2.5 mm and H 3.5 mm, located in the granular cell layer of the unilateral dentate gyrus (DG) of hippocampus, at the site of which an opening with the diameter of 1.5 mm was drilled for the purpose of embedding of the stimulating and recording

  15. Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

    Institute of Scientific and Technical Information of China (English)

    LI Ying; JI Yong-juan; JIANG Hong; LIU De-xiang; ZHANG Qian; FAN Shu-jian; PAN Fang

    2009-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals (age: F=6.173, P <0.05, stress: F=6.056, P <0.05). Stress was the main factor affecting sucrose preference (F=123.608, P <0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P <0.05). The older stress rats showed a lower sucrose preference than young stress rats (P <0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P <0.05), exhibiting fewer vertical movements (P <0.05) and less grooming (P <0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress

  16. Differential effects of the histamine H3 receptor agonist methimepip on dentate granule cell excitability, paired-pulse plasticity and long-term potentiation in prenatal alcohol-exposed rats

    Science.gov (United States)

    Varaschin, Rafael K.; Rosenberg, Martina J.; Hamilton, Derek A.; Savage, Daniel D.

    2016-01-01

    We previously reported that prenatal alcohol-induced deficits in dentate gyrus (DG) long-term potentiation (LTP) are ameliorated by the histamine H3 receptor inverse agonist ABT-239. ABT-239 did not enhance LTP in control rats, suggesting a heightened H3 receptor-mediated inhibition of glutamate release in prenatal alcohol-exposed (PAE) offspring. As the modulation of glutamate release is one important facet of LTP, we examined the effect of methimepip, a histamine H3 receptor agonist, on DG granule cell excitability, glutamate release and LTP in control and PAE rats. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution four hours daily throughout gestation. Male adult offspring were anesthetized with urethane and electrodes implanted into the entorhinal cortex and DG. PAE reduced coupling of excitatory post-synaptic field potentials to population spikes, an effect mimicked in control rats treated with 1 mg/kg methimepip. Methimepip decreased release probability in controls but not in PAE offspring. GABAergic feedback inhibition of granule cell responsiveness was not affected by either PAE or methimepip. PAE reduced LTP in the DG, another effect mimicked in methimepip-treated control rats. Again, methimepip did not exacerbate the PAE-induced LTP deficit. Thus, while methimepip treatment of control rats mimicked some baseline and activity-dependent deficits observed in saline-treated PAE offspring, methimepip treatment of PAE rats did not exacerbate these deficits. Whether the absence of an added methimepip effect in PAE offspring is a consequence of a “floor effect” for the responses measured or is due to differential drug dose responsiveness will require further investigation. Further, more detailed studies of H3 receptor-mediated responses in vitro may provide clearer insights into the role of the H3 receptor regulation of excitatory transmission at the perforant path - DG synapse in PAE rats. PMID:24818819

  17. Effects of the ephedra alkaloid methylephedrine on the basal evoked potential transportation and the long-term potentiation (LTP) in the rat hippocampal dentate granule cells in vivo

    Institute of Scientific and Technical Information of China (English)

    PENG Xiao-dong

    2008-01-01

    Objective The effect of the ephedra/ephedrine alkaloid methylephedrine (dl-methylephedrine hydrochloride for testing in this paper) on cognitive related synaptic plasticity was investigated by recording extracellular field evoked potentials and its LTP in hippocampal dentate granule cells in urethane-anaesthetized rats in vivo. Methods Single pathway recording of evoked field potentials was made from the dentate granule cells of hippocampal hemisphere in response to stimulation of the ipsilateral medial perforant path (MPP). Two parameters, the amplitude of population spike (PS amplitude) and the latency of the PS, were employed to evaluate the effects of drug on the overall changes in cellular responses. Results The present study show that methylephedrine 90 mg·kg-1 intraperitoneally, about 1/3 LD50, could increase the latency of the PS in hippocampal dentate granule cells by constant single stimulation of the MPP as the basal ransportation. However, the 30 mg·kg-1 and 10 mg·kg-1 dosage had no effect on the latency, and there are no influences of PS amplitude for all examinational groups. The methylephedrine 90 mg·kg-1 group significant enhanced the development of amplitude LTP in hippocampal dentate granule cells that induced by 60 Hz, 60 pulses conditional tetanus in medial perforant path area. Also, the 30 mg·kg-1 group can promoted the maintenance of LTP induced by this tetanus, but no promotion on PS amplitude LTP appeared in this dosage and no any changes been found in 10 mg·kg-1 dosage group. Conclusions The ephedra/ephedrine alkaloid methylephedrine can modulate the synaptic plasticity in the lateral perforant path. A possible mechanism of methylephedrine on hippocampal LTP is been discussed.

  18. Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

    Science.gov (United States)

    Pereira, Pedro A; Rocha, João P; Cardoso, Armando; Vilela, Manuel; Sousa, Sérgio; Madeira, M Dulce

    2016-05-01

    Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus.

  19. Fine processes of Nestin-GFP-positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature.

    Science.gov (United States)

    Moss, Jonathan; Gebara, Elias; Bushong, Eric A; Sánchez-Pascual, Irene; O'Laoi, Ruadhan; El M'Ghari, Imane; Kocher-Braissant, Jacqueline; Ellisman, Mark H; Toni, Nicolas

    2016-05-03

    Adult hippocampal neurogenesis relies on the activation of neural stem cells in the dentate gyrus, their division, and differentiation of their progeny into mature granule neurons. The complex morphology of radial glia-like (RGL) stem cells suggests that these cells establish numerous contacts with the cellular components of the neurogenic niche that may play a crucial role in the regulation of RGL stem cell activity. However, the morphology of RGL stem cells remains poorly described. Here, we used light microscopy and electron microscopy to examine Nestin-GFP transgenic mice and provide a detailed ultrastructural reconstruction analysis of Nestin-GFP-positive RGL cells of the dentate gyrus. We show that their primary processes follow a tortuous path from the subgranular zone through the granule cell layer and ensheathe local synapses and vasculature in the inner molecular layer. They share the ensheathing of synapses and vasculature with astrocytic processes and adhere to the adjacent processes of astrocytes. This extensive interaction of processes with their local environment could allow them to be uniquely receptive to signals from local neurons, glia, and vasculature, which may regulate their fate.

  20. Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats

    Directory of Open Access Journals (Sweden)

    Babar E.

    2002-01-01

    Full Text Available The interactions between the median raphe nucleus (MRN serotonergic system and the septohippocampal muscarinic cholinergic system in the modulation of immediate working memory storage performance were investigated. Rats with sham or ibotenic acid lesions of the MRN were bilaterally implanted with cannulae in the dentate gyrus of the hippocampus and tested in a light/dark step-through inhibitory avoidance task in which response latency to enter the dark compartment immediately after the shock served as a measure of immediate working memory storage. MRN lesion per se did not alter response latency. Post-training intrahippocampal scopolamine infusion (2 and 4 µg/side produced a more marked reduction in response latencies in the lesioned animals compared to the sham-lesioned rats. Results suggest that the immediate working memory storage performance is modulated by synergistic interactions between serotonergic projections of the MRN and the muscarinic cholinergic system of the hippocampus.

  1. Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats.

    Science.gov (United States)

    Greisen, Mia H; Altar, C Anthony; Bolwig, Tom G; Whitehead, Richard; Wörtwein, Gitta

    2005-03-15

    Repeated maternal separation of rat pups during the early postnatal period may affect brain-derived neurotrophic factor (BDNF) or neurons in brain areas that are compromised by chronic stress. In the present study, a highly significant increase in hippocampal BDNF protein concentration was found in adult rats that as neonates had been subjected to 180 min of daily separation compared with handled rats separated for 15 min daily. BDNF protein was unchanged in the frontal cortex and hypothalamus/paraventricular nucleus. Expression of BDNF mRNA in the CA1, CA3, or dentate gyrus of the hippocampus or in the paraventricular hypothalamic nucleus was not affected by maternal separation. All animals displayed similar behavioral patterns in a forced-swim paradigm, which did not affect BDNF protein concentration in the hippocampus or hypothalamus. Repeated administration of bromodeoxyuridine revealed equal numbers of surviving, newly generated granule cells in the dentate gyrus of adult rats from the 15 min or 180 min groups. The age-dependent decline in neurogenesis from 3 months to 7 months of age did not differ between the groups. Insofar as BDNF can stimulate neurogenesis and repair, we propose that the elevated hippocampal protein concentration found in maternally deprived rats might be a compensatory reaction to separation during the neonatal period, maintaining adult neurogenesis at levels equal to those of the handled rats.

  2. Differential paired-pulse responses between the CA1 region and the dentate gyrus are related to altered CLC-2 immunoreactivity in the pilocarpine-induced rat epilepsy model.

    Science.gov (United States)

    Kwak, Sung-Eun; Kim, Ji-Eun; Kim, Duk-Soo; Won, Moo Ho; Lee, Hong Jin; Choi, Soo-Young; Kwon, Oh-Shin; Kim, Jin-Sang; Kang, Tae-Cheon

    2006-10-18

    The epileptic hippocampus shows differential paired-pulse responses between the dentate gyrus and the CA1 region. However, little data are available to explain this phenomenon. In the present study, we identified the relationship between regional differences of paired-pulse response and voltage gated Cl(-) channel 2 (CLC-2)/vesicular GABA transport (VGAT) expression in a pilocarpine-induced rat model. During epileptogenic periods, paired-pulse inhibitions in the dentate gyrus and the CA1 region were markedly reduced. After recurrent seizure onset, paired-pulse inhibition in the dentate gyrus was markedly enhanced, while that in the CA1 region more reduced. Unlike VGAT, CLC-2 immunoreactivity was markedly reduced in the hippocampus during epileptogenic periods and was re-enhanced only in the dentate gyrus after recurrent seizure onset. Linear regression analysis showed an inverse proportional relationship between alterations in CLC-2 immunoreactivity and changes in normalized population spike amplitude ratio within the CA1 region and the dentate gyrus. Therefore, our findings suggest that the regionally specific alterations in CLC-2 immunoreactivity after SE may determine the properties of paired-pulse responses in the hippocampus of the pilocarpine-induced rat epilepsy model.

  3. BDNF Depresses Excitability of Parvalbumin-Positive Interneurons through an M-Like Current in Rat Dentate Gyrus

    OpenAIRE

    Jose Luis Nieto-Gonzalez; Kimmo Jensen

    2013-01-01

    In addition to their classical roles in neuronal growth, survival and differentiation, neurotrophins are also rapid regulators of excitability, synaptic transmission and activity-dependent synaptic plasticity. We have recently shown that mature BDNF (Brain Derived Neurotrophic Factor), but not proBDNF, modulates the excitability of interneurons in dentate gyrus within minutes. Here, we used brain slice patch-clamp recordings to study the mechanisms through which BDNF modulates the firing of i...

  4. NMDA-dependent mechanisms only affect the BOLD response in the rat dentate gyrus by modifying local signal processing

    Science.gov (United States)

    Tiede, Regina; Krautwald, Karla; Fincke, Anja; Angenstein, Frank

    2012-01-01

    The role of N-methyl--aspartate (NMDA) receptor-mediated mechanisms in the formation of a blood oxygen level-dependent (BOLD) response was studied using electrical stimulation of the right perforant pathway. Stimulation of this fiber bundle triggered BOLD responses in the right hippocampal formation and in the left entorhinal cortex. The perforant pathway projects to and activates the dentate gyrus monosynaptically, activation in the contralateral entorhinal cortex is multisynaptic and requires forwarding and processing of signals. Application of the NMDA receptor antagonist MK801 during stimulation had no effect on BOLD responses in the right dentate gyrus, but reduced the BOLD responses in the left entorhinal cortex. In contrast, application of MK801 before the first stimulation train reduced the BOLD response in both regions. Electrophysiological recordings revealed that the initial stimulation trains changed the local processing of the incoming signals in the dentate gyrus. This altered electrophysiological response was not further changed by a subsequent application of MK801, which is in agreement with an unchanged BOLD response. When MK801 was present during the first stimulation train, a dissimilar electrophysiological response pattern was observed and corresponds to an altered BOLD response, indicating that NMDA-dependent mechanisms indirectly affect the BOLD response, mainly via modifying local signal processing and subsequent propagation. PMID:22167232

  5. Differential effects of strain, circadian cycle, and stimulation pattern on LTP and concurrent LTD in the dentate gyrus of freely moving rats.

    Science.gov (United States)

    Bowden, Jared B; Abraham, Wickliffe C; Harris, Kristen M

    2012-06-01

    Because long-term potentiation (LTP) and long-term depression (LTD) are thought to be involved in learning and memory, it is important to delineate factors that modulate their induction and persistence, especially as studied in freely moving animals. Here, we investigated the effects of rat strain, circadian cycle, and high-frequency stimulation (HFS) pattern on LTP and concurrently induced LTD in the dentate gyrus (DG). Comparison of two commonly used rat strains revealed that medial perforant path field EPSP-population spike (E-S) coupling and LTP were greater in Long-Evans than Sprague-Dawley rats. Circadian cycle experiments conducted in Long-Evans rats revealed greater E-S coupling and enhanced LTP during the dark phase. Interestingly, concurrent LTD in the lateral perforant path did not significantly differ across strains or circadian cycle. Testing HFS protocols during the dark phase revealed that theta burst stimulation (100 Hz bursts at 5 Hz intervals) was ineffective in eliciting either LTP or concurrent LTD in DG, whereas 400 Hz bursts delivered at theta (5 Hz) or delta (1 Hz) frequencies produced substantial LTP and concurrent LTD. Thus, these natural and experimental factors regulate granule cell excitability, and differentially affect LTP and concurrent LTD in the DG of freely moving rats. © 2011 Wiley Periodicals, Inc.

  6. Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats

    Science.gov (United States)

    Shepherd, Daniel J.; Tsai, Shih-Yen; O'Brien, Timothy E.; Farrer, Robert G.; Kartje, Gwendolyn L.

    2016-01-01

    Ischemic stroke is a leading cause of adult disability, including cognitive impairment. Our laboratory has previously shown that treatment with function-blocking antibodies against the neurite growth inhibitory protein Nogo-A promotes functional recovery after stroke in adult and aged rats, including enhancing spatial memory performance, for which the hippocampus is critically important. Since spatial memory has been linked to hippocampal neurogenesis, we investigated whether anti-Nogo-A treatment increases hippocampal neurogenesis after stroke. Adult rats were subject to permanent middle cerebral artery occlusion followed 1 week later by 2 weeks of antibody treatment. Cellular proliferation in the dentate gyrus was quantified at the end of treatment, and the number of newborn neurons was determined at 8 weeks post-stroke. Treatment with both anti-Nogo-A and control antibodies stimulated the accumulation of new microglia/macrophages in the dentate granule cell layer, but neither treatment increased cellular proliferation or the number of newborn neurons above stroke-only levels. These results suggest that anti-Nogo-A immunotherapy does not increase post-stroke hippocampal neurogenesis. PMID:27803646

  7. Synaptic plasticity and the analysis of the field-EPSP as well as the population spike using separate recording electrodes in the dentate gyrus in freely moving rats.

    Science.gov (United States)

    Frey, Sabine; Frey, Julietta U

    2009-10-30

    Commonly, synaptic plasticity events such as long-term potentiation (LTP) are investigated by using a stimulation electrode and a single, monopolar field recording electrode in the dentate gyrus in intact, freely moving rats. The recording electrode is mostly positioned in the granular cell layer, or the hilar region of the dentate gyrus, i.e. far away from the place of generation of monosynaptic postsynaptic excitatory potentials (EPSP). Since LTP is a synaptic phenomenon and field recordings far away from the activated synapses do not guarantee a specific interpretation of the overlaid, mixture of complex potentials of several different electrical fields it is often difficult or even impossible to interpret the data obtained by such a single recording electrode. Therefore, at least a separate or two recording electrodes should be used to record the EPSP as well as the spike, respectively, ideally at their places of generation. Here, we describe a method by implanting a chronic bipolar recording electrode which fulfils the above requirements by recording the field-EPSP as well as the population spike at their places of generation and describe the time course of LTP measured using this "double-recording" electrode. We show that different tetanization protocols resulted in EPSP- or population spike-LTP but only if the potentials were recorded by electrodes positioned within adequate places of potential generation. Interestingly, the commonly used recording in the hilus of a distinct part of a potential, mistakenly analyzed as an "EPSP" did not reveal any LTP.

  8. Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain

    Institute of Scientific and Technical Information of China (English)

    Sung Jin Kwon; Jeongsook Park; So Yun Park; Kwang Seop Song; Sun Tae Jung; So Bong Jung; Ik Ryeul Park; Wan Sung Choi; Sun Ok Kwon

    2013-01-01

    The hippocampus is a brain region responsible for learning and memory functions. The purpose of this study was to investigate the effects of low-intensity exercise and bright light exposure on neurogenesis and brain-derived neurotrophic factor expression in adult rat hippocampus. Male Sprague-Dawley rats were randomly assigned to control, exercise, light, or exercise + light groups (n = 9 per group). The rats in the exercise group were subjected to treadmill exercise (5 days per week, 30 minutes per day, over a 4-week period), the light group rats were irradiated (5 days per week, 30 minutes per day, 10 000 lx, over a 4-week period), the exercise + light group rats were subjected to treadmill exercise in combination with bright light exposure, and the control group rats remained sedentary over a 4-week period. Compared with the control group, there was a significant increase in neurogenesis in the hippocampal dentate gyrus of rats in the exercise, light, and exercise + light groups. Moreover, the expression level of brain-derived neurotrophic factor in the rat hippocampal dentate gyrus was significantly higher in the exercise group and light group than that in the control group. Interestingly, there was no significant difference in brain-derived neurotrophic factor expression between the control group and exercise + light group. These results indicate that low-intensity treadmill exercise (first 5 minutes at a speed of 2 m/min, second 5 minutes at a speed of 5 m/min, and the last 20 minutes at a speed of 8 m/min) or bright-light exposure therapy induces positive biochemical changes in the brain. In view of these findings, we propose that moderate exercise or exposure to sunlight during childhood can be beneficial for neural development.

  9. Effects of Buyang Huanwu decoction on cell proliferation and differentiation in the hippocampal dentate gyrus of aged rats following cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Jianfeng Gao; Fenghua Lü; Changlian Zhu

    2009-01-01

    BACKGROUND: The mobilization of endogenous stem cells is an effective way to promote repair following ischemic brain damage. Buyang Huanwu decoction (BHD) can effectively improve cerebral blood flow and protect against cerebral ischemia/reperfusion damage.OBJECTIVE: To study the effects of BHD on cell proliferation and differentiation in the hippocampal dentate gyrus of rats following cerebral infarction, to investigate the protective effects of BHD against cerebral infarction, and to analyze the dose-effect relationship.DESIGN, TIME AND SETTING: This randomized, controlled, animal study was performed at the Laboratory of Department of Physiology, Henan College of Traditional Chinese Medicine, China from June 2007 to February 2008.MATERIALS: A total of 36 male, Sprague Dawley rats, aged 20-21 months, were equally and randomly assigned to the following groups: sham operation, model control, and nimodipine, as well as high-dose, moderate-dose, and low-dose BHD. BHD was composed of milkvetch root, Chinese angelica, red peony root, earthworm, peach seed, safflower, and Szechwan Iovage rhizome, which were provided by the Outpatient Department, Henan College of Traditional Chinese Medicine, China.METHODS: The Chinese medicinal ingredients described above were decocted. The external carotid artery was ligated in rats from the sham operation group. Rat models of focal cerebral infarction were established by middle cerebral artery occlusion in the model control and nimodipine groups, as well as the high-dose, moderate-dose, and low-dose BHD groups. The drugs were administered by gavage 5 days, as well as 2 hours, prior to model induction. Rats in the nimodipine group were daily administered a 6 mg/kg nimodipine suspension by gavage. Rats in the high-dose, moderate-dose, and low-dose BHD groups were administered daily 26, 13, and 6.5 g/kg BHD, respectively. Rats in the sham operation and model control groups were treated with an equal volume of saline.MAIN OUTCOME MEASURES

  10. Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat

    DEFF Research Database (Denmark)

    Madsen, Torsten Meldgaard; Kristjansen, P.E.G.; Bolwig, Tom Gert

    2003-01-01

    The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain...... days after irradiation, the animals with blocked neurogenesis performed poorer than controls in a hippocampus-dependent place-recognition task, indicating that the presence of newly generated neurons may be necessary for the normal function of this brain area. The animals were never impaired...... irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21...

  11. Age-related impairment of long-term depression in area CA1 and dentate gyrus of rat hippocampus following developmental lead exposure in vitro.

    Science.gov (United States)

    Sui, L; Ge, S Y; Ruan, D Y; Chen, J T; Xu, Y Z; Wang, M

    2000-01-01

    Chronic developmental lead exposure is known to be associated with cognitive dysfunction in children. Impairment of the induction of long-term depression (LTD) has been reported in area CA1 and dentate gyrus (DG) of rat hippocampus following chronic lead exposure. The present study was carried out to investigate age-related alterations of LTD in area CA1 and DG of rat hippocampus following developmental lead exposure in vitro. Neonatal Wistar rats were exposed to lead from parturition to weaning via milk of dams drinking 0.2% lead acetate solution. Field excitatory postsynaptic potentials (EPSPs) were recorded in hippocampal slices at various postnatal ages: postnatal day (PND) 17-23, 27-33, and 57-63. Following low-frequency stimulation (LFS, 900 pulses/1 Hz), the average magnitude of LTD is age related. In the controls, LTD magnitude in area CA1 decreased with age, whereas in DG it increased with age. In the lead-exposed groups, the magnitude of LTD declined during development in both area CA1 and DG. The differences of LTD magnitude between the control and lead-exposed rats were 27.26 +/- 9.15% (PND 17-23), 21.59 +/- 12.93% (PND 27-33), and 16.96 +/- 9.33% (PND 57-63) in area CA1, and were 6.95 +/- 9.26%, 17.60 +/- 3.91%, and 33.63 +/- 10.47% in DG, respectively. These results demonstrated that the lead-induced impairment of LTD magnitude was an age-related decline in area CA1 and an age-related increase in area DG of rat hippocampus. Published by Elsevier Science Inc.

  12. Early maternal deprivation affects dentate gyrus structure and emotional learning in adult female rats

    NARCIS (Netherlands)

    Oomen, C.A.; Soeters, H.; Audureau, N.; Vermunt, L.; van Hasselt, F.N.; Manders, E.M.M.; Joëls, M.; Krugers, H.; Lucassen, P.J.

    2011-01-01

    Rationale: Stress elicits functional and structural changes in the hippocampus. Early life stress is one of the major risk factors for stress-related pathologies like depression. Patients suffering from depression show a reduced hippocampal volume, and in women, this occurs more often when depressio

  13. Previous history of chronic stress changes the transcriptional response to glucocorticoid challenge in the dentate gyrus region of the male rat hippocampus.

    Science.gov (United States)

    Datson, Nicole A; van den Oever, Jessica M E; Korobko, Oksana B; Magarinos, Ana Maria; de Kloet, E Ronald; McEwen, Bruce S

    2013-09-01

    Chronic stress is a risk factor for several neuropsychiatric diseases, such as depression and psychosis. In response to stress glucocorticoids (GCs) are secreted that bind to mineralocorticoid and glucocorticoid receptors, ligand-activated transcription factors that regulate the transcription of gene networks in the brain necessary for coping with stress, recovery, and adaptation. Chronic stress particularly affects the dentate gyrus (DG) subregion of the hippocampus, causing several functional and morphological changes with consequences for learning and memory, which are likely adaptive but at the same time make DG neurons more vulnerable to subsequent challenges. The aim of this study was to investigate the transcriptional response of DG neurons to a GC challenge in male rats previously exposed to chronic restraint stress (CRS). An intriguing finding of the current study was that having a history of CRS had profound consequences for the subsequent response to acute GC challenge, differentially affecting the expression of several hundreds of genes in the DG compared with challenged nonstressed control animals. This enduring effect of previous stress exposure suggests that epigenetic processes may be involved. In line with this, CRS indeed affected the expression of several genes involved in chromatin structure and epigenetic processes, including Asf1, Ash1l, Hist1h3f, and Tp63. The data presented here indicate that CRS alters the transcriptional response to a subsequent GC injection. We propose that this altered transcriptional potential forms part of the molecular mechanism underlying the enhanced vulnerability for stress-related disorders like depression caused by chronic stress.

  14. The role of topography in the transformation of spatiotemporal patterns by a large-scale, biologically realistic model of the rat dentate gyrus.

    Science.gov (United States)

    Yu, Gene J; Hendrickson, Phillip J; Robinson, Brian S; Song, Dong; Berger, Theodore W

    2013-01-01

    A large-scale, biologically realistic, computational model of the rat hippocampus is being constructed to study the input-output transformation that the hippocampus performs. In the initial implementation, the layer II entorhinal cortex neurons, which provide the major input to the hippocampus, and the granule cells of the dentate gyrus, which receive the majority of the input, are modeled. In a previous work, the topography, or the wiring diagram, connecting these two populations had been derived and implemented. This paper explores the consequences of two features of the topography, the distribution of the axons and the size of the neurons' axon terminal fields. The topography converts streams of independently generated random Poisson trains into structured spatiotemporal patterns through spatiotemporal convergence achievable by overlapping axon terminal fields. Increasing the axon terminal field lengths allowed input to converge over larger regions of space resulting in granule activation across a greater area but did not increase the total activity as a function of time as the number of targets per input remained constant. Additional simulations demonstrated that the total distribution of spikes in space depends not on the distribution of the presynaptic axons but the distribution of the postsynaptic population. Analyzing spike counts emphasizes the importance of the postsynaptic distribution, but it ignores the fact that each individual input may be carrying unique information. Therefore, a metric should be created that relates and tracks individual inputs as they are propagated and integrated through hippocampus.

  15. Organization of multisynaptic inputs to the dorsal and ventral dentate gyrus: retrograde trans-synaptic tracing with rabies virus vector in the rat.

    Directory of Open Access Journals (Sweden)

    Shinya Ohara

    Full Text Available Behavioral, anatomical, and gene expression studies have shown functional dissociations between the dorsal and ventral hippocampus with regard to their involvement in spatial cognition, emotion, and stress. In this study we examined the difference of the multisynaptic inputs to the dorsal and ventral dentate gyrus (DG in the rat by using retrograde trans-synaptic tracing of recombinant rabies virus vectors. Three days after the vectors were injected into the dorsal or ventral DG, monosynaptic neuronal labeling was present in the entorhinal cortex, medial septum, diagonal band, and supramammillary nucleus, each of which is known to project to the DG directly. As in previous tracing studies, topographical patterns related to the dorsal and ventral DG were seen in these regions. Five days after infection, more of the neurons in these regions were labeled and labeled neurons were also seen in cortical and subcortical regions, including the piriform and medial prefrontal cortices, the endopiriform nucleus, the claustrum, the cortical amygdala, the medial raphe nucleus, the medial habenular nucleus, the interpeduncular nucleus, and the lateral septum. As in the monosynaptically labeled regions, a topographical distribution of labeled neurons was evident in most of these disynaptically labeled regions. These data indicate that the cortical and subcortical inputs to the dorsal and ventral DG are conveyed through parallel disynaptic pathways. This second-order input difference in the dorsal and ventral DG is likely to contribute to the functional differentiation of the hippocampus along the dorsoventral axis.

  16. Enhanced deficits in long-term potentiation in the adult dentate gyrus with 2nd trimester ethanol consumption.

    Directory of Open Access Journals (Sweden)

    Jennifer L Helfer

    Full Text Available Ethanol exposure during pregnancy can cause structural and functional changes in the brain that can impair cognitive capacity. The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of ethanol. In the present experiments we sought to determine if the functional effects of developmental ethanol exposure could be linked to ethanol exposure during any single trimester-equivalent. Ethanol exposure during the 1(st or 3(rd trimester-equivalent produced only minor changes in synaptic plasticity in adult offspring. In contrast, ethanol exposure during the 2(nd trimester equivalent resulted in a pronounced decrease in long-term potentiation, indicating that the timing of exposure influences the severity of the deficit. Together, the results from these experiments demonstrate long-lasting alterations in synaptic plasticity as the result of developmental ethanol exposure and dependent on the timing of exposure. Furthermore, these results allude to neural circuit malfunction within the hippocampal formation, perhaps relating to the learning and memory deficits observed in individuals with fetal alcohol spectrum disorders.

  17. Early life stress enhancement of limbic epileptogenesis in adult rats: mechanistic insights.

    Directory of Open Access Journals (Sweden)

    Gaurav Kumar

    Full Text Available BACKGROUND: Exposure to early postnatal stress is known to hasten the progression of kindling epileptogenesis in adult rats. Despite the significance of this for understanding mesial temporal lobe epilepsy (MTLE and its associated psychopathology, research findings regarding underlying mechanisms are sparse. Of several possibilities, one important candidate mechanism is early life 'programming' of the hypothalamic-pituitary-adrenal (HPA axis by postnatal stress. Elevated corticosterone (CORT in turn has consequences for neurogenesis and cell death relevant to epileptogenesis. Here we tested the hypotheses that MS would augment seizure-related corticosterone (CORT release and enhance neuroplastic changes in the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: Eight-week old Wistar rats, previously exposed on postnatal days 2-14 to either maternal separation stress (MS or control brief early handling (EH, underwent rapid amygdala kindling. We measured seizure-induced serum CORT levels and post-kindling neurogenesis (using BrdU. Three weeks post-kindling, rats were euthanized for histology of the hippocampal CA3c region (pyramidal cell counts and dentate gyrus (DG (to count BrdU-labelled cells and measure mossy fibre sprouting. As in our previous studies, rats exposed to MS had accelerated kindling rates in adulthood. Female MS rats had heightened CORT responses during and after kindling (p<0.05, with a similar trend in males. In both sexes total CA3c pyramidal cell numbers were reduced in MS vs. EH rats post-kindling (p = 0.002. Dentate granule cell neurogenesis in female rats was significantly increased post-kindling in MS vs. EH rats. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that early life stress results in enduring enhancement of HPA axis responses to limbic seizures, with increased hippocampal CA3c cell loss and augmented neurogenesis, in a sex-dependent pattern. This implicates important candidate mechanisms through which early life

  18. Seipin knockout in mice impairs stem cell proliferation and progenitor cell differentiation in the adult hippocampal dentate gyrus via reduced levels of PPARγ

    Directory of Open Access Journals (Sweden)

    Guoxi Li

    2015-12-01

    Full Text Available The seipin gene (BSCL2 was originally identified in humans as a loss-of-function gene associated with congenital generalized lipodystrophy type 2 (CGL2. Neuronal seipin-knockout (seipin-nKO mice display a depression-like phenotype with a reduced level of hippocampal peroxisome proliferator-activated receptor gamma (PPARγ. The present study investigated the influence of seipin deficiency on adult neurogenesis in the hippocampal dentate gyrus (DG and the underlying mechanisms of the effects. We show that the proliferative capability of stem cells in seipin-nKO mice was substantially reduced compared to in wild-type (WT mice, and that this could be rescued by the PPARγ agonist rosiglitazone (rosi. In seipin-nKO mice, neuronal differentiation of progenitor cells was inhibited, with the enhancement of astrogliogenesis; both of these effects were recovered by rosi treatment during early stages of progenitor cell differentiation. In addition, rosi treatment could correct the decline in hippocampal ERK2 phosphorylation and cyclin A mRNA level in seipin-nKO mice. The MEK inhibitor U0126 abolished the rosi-rescued cell proliferation and cyclin A expression in seipin-nKO mice. In seipin-nKO mice, the hippocampal Wnt3 protein level was less than that in WT mice, and there was a reduction of neurogenin 1 (Neurog1 and neurogenic differentiation 1 (NeuroD1 mRNA, levels of which were corrected by rosi treatment. STAT3 phosphorylation (Tyr705 was enhanced in seipin-nKO mice, and was further elevated by rosi treatment. Finally, rosi treatment for 10 days could alleviate the depression-like phenotype in seipin-nKO mice, and this alleviation was blocked by the MEK inhibitor U0126. The results indicate that, by reducing PPARγ, seipin deficiency impairs proliferation and differentiation of neural stem and progenitor cells, respectively, in the adult DG, which might be responsible for the production of the depression-like phenotype in seipin-nKO mice.

  19. Effects of mild hypothermia on the expression of microtubule-associated protein 2 in neurons of the hippocampal dentate gyrus in a rat model of cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Qian Yang; Feng Zheng; Jiami Wu

    2008-01-01

    BACKGROUND: It is widely accepted that mild hypothermia can protect against injury to cerebral ischemia/reperfusion.OBJECTIVE: To observe the effects of mild hypothermia on microtubule-associated protein 2 (MAP2) expression in the hippocampal dentate gyrus in rats following cerebral ischemia/reperfusion. Also, to study neuronal uhrastructural changes in the dentate gyrus to investigate the mechanism of the protection against injury to cerebral ischemia/reperfusion conferred by mild hypothermia.DESIGN, TIME AND SETTING: This randomized grouping, neural cell morphology trial was performed at the Laboratory Animal Center of Yijishan Hospital between March and June 2007.MATERIALS: Eighty-five healthy male Sprague Dawley rats were randomly allocated to three groups: mild hyputhermia (n = 40), normothermia (n = 40), and sham-operated (n = 5).METHODS: Cerebral ischemia/reperfusion injury was induced by the suture method in the mild hypothermia and normothermia groups, with a threading depth of 180.5 mm. In the sham-operated group, the suture was inserted 15 mm, with no vascular ligation, and was followed by reperfusion 2 hours later. In the sham-operated and normothermia groups, the rat rectal temperature was maintained at 36-37℃; in the mild hypothermia group, it was controlled at 32-33 ℃.MAIN OUTCOME MEASURES: The hippocampal dentate gyrus was serially sectioned for hematoxylin-eosin staining and MAP2 immunohistochemistry. Ultrastructural changes and the MAP2 absorbance value of the hippocampal dentate gyrus were examined by transmission electron microscopy.RESULTS: The sham-operated group exhibited approximately normal ultrastmcture of neurons in the bilateral hippocampal dentate gyms. In the normothermia group, ischemic hippocampal dentate gyms neurons were found with markedly fewer normal mitochondria, greatly proliferated rough endoplasmic reticulum, and a swollen and dysmorphic Golgi. In the mild hypothermia group, at each corresponding time point, these

  20. Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats

    OpenAIRE

    R A Kireev; Vara, E. (E.); Tresguerres, J. A. F.

    2013-01-01

    It has been suggested that the age-related decrease in the number of neurons in the hippocampus that leads to alterations in brain function, may be associated with an increase in apoptosis due to the reduced secretion of growth hormone (GH) and/or melatonin in old animals. In order to investigate this possibility, male Wistar rats of 22 months of age were divided into three groups. One group remained untreated and acted as the control group. The second was treated with growth hormone (hGH) fo...

  1. A Transient Upregulation of Glutamine Synthetase in the Dentate Gyrus Is Involved in Epileptogenesis Induced by Amygdala Kindling in the Rat.

    Directory of Open Access Journals (Sweden)

    Hong-Liu Sun

    Full Text Available Reduction of glutamine synthetase (GS function is closely related to established epilepsy, but little is known regarding its role in epileptogenesis. The present study aimed to elucidate the functional changes of GS in the brain and its involvement in epileptogenesis using the amygdala kindling model of epilepsy induced by daily electrical stimulation of basolateral amygdala in rats. Both expression and activity of GS in the ipsilateral dentate gyrus (DG were upregulated when kindled seizures progressed to stage 4. A single dose of L-methionine sulfoximine (MSO, in 2 µl, a selective GS inhibitor, was administered into the ipsilateral DG on the third day following the first stage 3 seizure (just before GS was upregulated. It was found that low doses of MSO (5 or 10 µg significantly and dose-dependently reduced the severity of and susceptibility to evoked seizures, whereas MSO at a high dose (20 µg aggravated kindled seizures. In animals that seizure acquisition had been successfully suppressed with 10 µg MSO, GS upregulation reoccurred when seizures re-progressed to stage 4 and re-administration of 10 µg MSO consistently reduced the seizures. GLN at a dose of 1.5 µg abolished the alleviative effect of 10 µg MSO and deleterious effect of 20 µg MSO on kindled seizures. Moreover, appropriate artificial microRNA interference (1 and 1.5×10(6 TU/2 µl of GS expression in the ipsilateral DG also inhibited seizure progression. In addition, a transient increase of GS expression and activity in the cortex was also observed during epileptogenesis evoked by pentylenetetrazole kindling. These results strongly suggest that a transient and region-specific upregulation of GS function occurs when epilepsy develops into a certain stage and eventually promotes the process of epileptogenesis. Inhibition of GS to an adequate degree and at an appropriate timing may be a potential therapeutic approach to interrupting epileptogenesis.

  2. An associativity requirement for locus coeruleus-induced long-term potentiation in the dentate gyrus of the urethane-anesthetized rat.

    Science.gov (United States)

    Reid, Andrew T; Harley, Carolyn W

    2010-01-01

    Norepinephrine has been hypothesized to provide a learning and memory signal. Norepinephrine long-term potentiation of perforant path input to the dentate gyrus of the hippocampus provides a model for norepinephrine initiated memory processes. However, in vitro, the pairing of perforant path stimulation and norepinephrine is not required for the occurrence of norepinephrine-dependent long-term potentiation. Since bath application of norepinephrine induces long-term changes in 2nd messenger signalling and differs in a number of ways from physiological norepinephrine release, the present study is an in vivo test of the associative requirement for the pairing of perforant path input with norepinephrine to induce long-term potentiation. Phasic activation of the locus coeruleus is provided by glutamate infusion into the locus coeruleus to initiate transient norepinephrine release in the hippocampus of urethane-anesthetized Sprague-Dawley rats. Perforant path stimulation (0.067 Hz) was given throughout the experiment in the paired condition. In the unpaired condition perforant path stimulation was interrupted 10 min prior to locus coeruleus activation and resumed 10 min after locus coeruleus activation. Locus coeruleus-induced long-term potentiation of both EPSP slope and population spike only occurred in the pairing condition. This result argues that, in vivo, temporal proximity of locus coeruleus-associated norepinephrine release and perforant path stimulation are required to induce long-term plasticity. The associativity requirement for locus coeruleus activation and perforant path stimulation in vivo is consistent with the hypothesis that norepinephrine can initiate circuit changes supporting learning and memory.

  3. Blockade of NMDA receptor subtype NR2B prevents seizures but not apoptosis of dentate gyrus neurons in bacterial meningitis in infant rats

    Directory of Open Access Journals (Sweden)

    Täuber Martin G

    2003-09-01

    Full Text Available Abstract Background Excitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis. The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S-alpha-(4-hydroxyphenyl-beta-methyl-4-(phenylmethyl-1-piperid inepropanol (RO 25-6981. Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae. Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28 or 3.75 mg (150 mg/kg; n = 15 every 3 h or an equal volume of sterile saline (250 μl; n = 40 starting at 12 h after infection. Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h. At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus. Results Treatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P Conclusions Treatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures.

  4. A Transient Upregulation of Glutamine Synthetase in the Dentate Gyrus Is Involved in Epileptogenesis Induced by Amygdala Kindling in the Rat

    Science.gov (United States)

    Zhong, Kai; Xu, Zheng-Hao; Feng, Bo; Yu, Jie; Fang, Qi; Wang, Shuang; Wu, Deng-Chang; Zhang, Jian-Min; Chen, Zhong

    2013-01-01

    Reduction of glutamine synthetase (GS) function is closely related to established epilepsy, but little is known regarding its role in epileptogenesis. The present study aimed to elucidate the functional changes of GS in the brain and its involvement in epileptogenesis using the amygdala kindling model of epilepsy induced by daily electrical stimulation of basolateral amygdala in rats. Both expression and activity of GS in the ipsilateral dentate gyrus (DG) were upregulated when kindled seizures progressed to stage 4. A single dose of L-methionine sulfoximine (MSO, in 2 µl), a selective GS inhibitor, was administered into the ipsilateral DG on the third day following the first stage 3 seizure (just before GS was upregulated). It was found that low doses of MSO (5 or 10 µg) significantly and dose-dependently reduced the severity of and susceptibility to evoked seizures, whereas MSO at a high dose (20 µg) aggravated kindled seizures. In animals that seizure acquisition had been successfully suppressed with 10 µg MSO, GS upregulation reoccurred when seizures re-progressed to stage 4 and re-administration of 10 µg MSO consistently reduced the seizures. GLN at a dose of 1.5 µg abolished the alleviative effect of 10 µg MSO and deleterious effect of 20 µg MSO on kindled seizures. Moreover, appropriate artificial microRNA interference (1 and 1.5×106 TU/2 µl) of GS expression in the ipsilateral DG also inhibited seizure progression. In addition, a transient increase of GS expression and activity in the cortex was also observed during epileptogenesis evoked by pentylenetetrazole kindling. These results strongly suggest that a transient and region-specific upregulation of GS function occurs when epilepsy develops into a certain stage and eventually promotes the process of epileptogenesis. Inhibition of GS to an adequate degree and at an appropriate timing may be a potential therapeutic approach to interrupting epileptogenesis. PMID:23825580

  5. A circuit-based gatekeeper for adult neural stem cell proliferation: Parvalbumin-expressing interneurons of the dentate gyrus control the activation and proliferation of quiescent adult neural stem cells.

    Science.gov (United States)

    Moss, Jonathan; Toni, Nicolas

    2013-01-01

    Newborn neurons are generated in the adult hippocampus from a pool of self-renewing stem cells located in the subgranular zone (SGZ) of the dentate gyrus. Their activation, proliferation, and maturation depend on a host of environmental and cellular factors but, until recently, the contribution of local neuronal circuitry to this process was relatively unknown. In their recent publication, Song and colleagues have uncovered a novel circuit-based mechanism by which release of the neurotransmitter, γ-aminobutyric acid (GABA), from parvalbumin-expressing (PV) interneurons, can hold radial glia-like (RGL) stem cells of the adult SGZ in a quiescent state. This tonic GABAergic signal, dependent upon the activation of γ(2) subunit-containing GABA(A) receptors of RGL stem cells, can thus prevent their proliferation and subsequent maturation or return them to quiescence if previously activated. PV interneurons are thus capable of suppressing neurogenesis during periods of high network activity and facilitating neurogenesis when network activity is low.

  6. Intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Ogawa, Taisuke; Takada, Shunsuke; Nakamura, Masatoshi; Fujii, Hiroaki; Ando, Masaki

    2014-11-01

    The role of perforant pathway-dentate granule cell synapses in cognitive behavior was examined focusing on synaptic Zn(2+) signaling in the dentate gyrus. Object recognition memory was transiently impaired when extracellular Zn(2+) levels were decreased by injection of clioquinol and N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylendediamine. To pursue the effect of the loss and/or blockade of Zn(2+) signaling in dentate granule cells, ZnAF-2DA (100 pmol, 0.1 mM/1 µl), an intracellular Zn(2+) chelator, was locally injected into the dentate molecular layer of rats. ZnAF-2DA injection, which was estimated to chelate intracellular Zn(2+) signaling only in the dentate gyrus, affected object recognition memory 1 h after training without affecting intracellular Ca(2+) signaling in the dentate molecular layer. In vivo dentate gyrus long-term potentiation (LTP) was affected under the local perfusion of the recording region (the dentate granule cell layer) with 0.1 mM ZnAF-2DA, but not with 1-10 mM CaEDTA, an extracellular Zn(2+) chelator, suggesting that the blockade of intracellular Zn(2+) signaling in dentate granule cells affects dentate gyrus LTP. The present study demonstrates that intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory, probably via dentate gyrus LTP expression.

  7. Impaired recruitment of seizure-generated neurons into functional memory networks of the adult dentate gyrus following long-term amygdala kindling.

    Science.gov (United States)

    Fournier, Neil M; Botterill, Justin J; Marks, Wendie N; Guskjolen, Axel J; Kalynchuk, Lisa E

    2013-06-01

    Epileptic seizures increase the birth of new neurons in the adult hippocampus. Although the consequences of aberrant neurogenesis on behavior are not fully understood, one hypothesis is that seizure-generated neurons might form faulty circuits that disrupt hippocampal functions, such as learning and memory. In the present study, we employed long-term amygdala kindling (i.e., rats receive 99-electrical stimulations) to examine the effect of repeated seizures on hippocampal neurogenesis and behavior. We labeled seizure-generated cells with the proliferation marker BrdU after 30-stimulations and continued kindling for an additional 4weeks to allow newborn neurons to mature under conditions of repeated seizures. After kindling was complete, rats were tested in a trace fear conditioning task and sacrificed 2h later to examine if 4-week old newborn cells were recruited into circuits involved in the retrieval of emotional memory. Compared to non-kindled controls, long-term kindled rats showed significant impairments in fear memory reflected in a decrease in conditioned freezing to both tone and contextual cues during testing. Moreover, long-term kindling also prevented the activation of 4-week old newborn cells in response to fear memory retrieval. These results indicate that the presence of seizure activity during cell maturation impedes the ability of new neurons to integrate properly into circuits important in memory formation. Together, our findings suggest that aberrant seizure-induced neurogenesis might contribute to the development of learning impairments in chronic epilepsy and raise the possibility that targeting the reduced activation of adult born neurons could represent a beneficial strategy to reverse cognitive deficits in some epileptic patients.

  8. Prolonged induction of c-fos in neuropeptide Y- and somatostatin-immunoreactive neurons of the rat dentate gyrus after electroconvulsive stimulation

    DEFF Research Database (Denmark)

    Woldbye, D P; Greisen, M H; Bolwig, T G;

    1996-01-01

    Induction of c-fos mRNA and Fos was studied in the hilus and granular layer of the dentate gyrus at various times up to 24 h after single electroconvulsive stimulation (ECS) using in situ hybridization and immunocytochemistry. In both areas of the dentate gyrus, a prominent induction of c-fos m....../or somatostatin (SS). Using double-labelling immunocytochemistry, we examined to what extent Fos was induced in these hilar neurons after ECS. Although a minor population of non-NPY non-SS cells displayed Fos induction early after ECS, prolonged induction of Fos almost exclusively occurred in NPY or SS neurons...

  9. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

    Science.gov (United States)

    Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

    2016-03-24

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

  10. Circadian variations in expression of the trkB receptor in adult rat hippocampus.

    Science.gov (United States)

    Dolci, Claudia; Montaruli, Angela; Roveda, Eliana; Barajon, Isabella; Vizzotto, Laura; Grassi Zucconi, Gigliola; Carandente, Franca

    2003-12-19

    The expression of brain-derived neurotrophic factor (BDNF) in the central nervous system (CNS) and the expression of its high-affinity trkB receptor on neuron surfaces are known to depend on neuron activity. The expression of BDNF (mRNA and protein) and trkB mRNA shows circadian oscillations in rat hippocampal homogenates. We investigated circadian variations in trkB expression in specific areas of the adult rat hippocampal formation by immunohistochemistry. In sets of two experiments performed in the spring, 39 2-month-old male Wistar rats were accustomed to a 12-h light-12-h dark cycle for 2 weeks. Three animals were then sacrificed every 4 h. Forty-micrometer-thick coronal sections of hippocampal formation were obtained and processed for trkB immunohistochemistry. Cell staining intensity was assessed by image analysis of different hippocampal areas on five sections per animal. Circadian rhythmicity was evaluated by the cosinor method. Statistically significant circadian variations in trkB expression were found in dentate gyrus, entorhinal cortex, and the CA3 and hilar regions of the hippocampus, with highest expression during the first half of the dark (activity) period. These findings suggest a relationship between trkB expression and the physiological neuronal activation of wakefulness. TrkB receptor expression in the hippocampal regions studied was continuous and changes were gradual over the 24-h cycle, suggesting that more complex regulatory mechanisms also intervened.

  11. An associativity requirement for locus coeruleus-induced long-term potentiation in the dentate gyrus of the urethane-anesthetized rat.

    NARCIS (Netherlands)

    Reid, A.T.; Harley, C.W.

    2010-01-01

    Norepinephrine has been hypothesized to provide a learning and memory signal. Norepinephrine long-term potentiation of perforant path input to the dentate gyrus of the hippocampus provides a model for norepinephrine initiated memory processes. However, in vitro, the pairing of perforant path stimula

  12. Repeated morphine treatment alters polysialylated neural cell adhesion molecule, glutamate decarboxylase-67 expression and cell proliferation in the adult rat hippocampus.

    Science.gov (United States)

    Kahn, Laëtitia; Alonso, Gérard; Normand, Elisabeth; Manzoni, Olivier J

    2005-01-01

    Altered synaptic transmission and plasticity in brain areas involved in reward and learning are thought to underlie the long-lasting effects of addictive drugs. In support of this idea, opiates reduce neurogenesis [A.J. Eisch et al. (2000) Proceedings of the National Academy of Sciences USA, 97, 7579-7584] and enhance long-term potentiation in adult rodent hippocampus [J.M. Harrison et al. (2002) Journal of Neurophysiology, 87, 2464-2470], a key structure of learning and memory processes. Here we studied how repeated morphine treatment and withdrawal affect cell proliferation and neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus. Our data showed a strong reduction of cellular proliferation in morphine-dependent animals (54% of control) that was followed by a rebound increase after 1 week withdrawal and a return to normal after 2 weeks withdrawal. Morphine dependence was also associated with a drastic reduction in the expression levels of the polysialylated form of neural cell adhesion molecule (68% of control), an adhesion molecule expressed by newly generated neurons and involved in cell migration and structural plasticity. Polysialylated neural cell adhesion molecule levels quickly returned to normal following withdrawal. In morphine-dependent rats, we found a significant increase of glutamate decarboxylase-67 mRNA transcription (170% of control) in dentate gyrus granular cells which was followed by a marked rebound decrease after 1 week withdrawal and a return to normal after 4 weeks withdrawal. Together, the results show, for the first time, that, in addition to reducing cell proliferation and neurogenesis, chronic exposure to morphine dramatically alters neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus.

  13. Characterization of dsRed2-positive cells in the doublecortin-dsRed2 transgenic adult rat retina.

    Science.gov (United States)

    Trost, A; Schroedl, F; Marschallinger, J; Rivera, F J; Bogner, B; Runge, C; Couillard-Despres, S; Aigner, L; Reitsamer, H A

    2014-12-01

    Doublecortin (DCX) is predominantly expressed in neuronal precursor cells and young immature neurons of the developing and adult brain, where it is involved in neuronal differentiation, migration and plasticity. Moreover, its expression pattern reflects neurogenesis, and transgenic DCX promoter-driven reporter models have been previously used to investigate adult neurogenesis. In this study, we characterize dsRed2 reporter protein-expressing cells in the adult retina of the transgenic DCX promoter-dsRed2 rat model, with the aim to identify cells with putative neurogenic activity. Additionally, we confirmed the expression of the dsRed2 protein in DCX-expressing cells in the adult hippocampal dentate gyrus. Adult DCX-dsRed2 rat retinas were analyzed by immunohistochemistry for expression of DCX, NF200, Brn3a, Sox2, NeuN, calbindin, calretinin, PKC-a, Otx2, ChAT, PSA-NCAM and the glial markers GFAP and CRALBP, followed by confocal laser-scanning microscopy. In addition, brain sections of transgenic rats were analyzed for dsRed2 expression and co-localization with DCX, NeuN, GFAP and Sox2 in the cortex and dentate gyrus. Endogenous DCX expression in the adult retina was confined to horizontal cells, and these cells co-expressed the DCX promoter-driven dsRed2 reporter protein. In addition, we encountered dsRed2 expression in various other cell types in the retina: retinal ganglion cells (RGCs), a subpopulation of amacrine cells, a minority of bipolar cells and in perivascular cells. Since also RGCs expressed dsRed2, the DCX-dsRed2 rat model might offer a useful tool to study RGCs in vivo under various conditions. Müller glial cells, which have previously been identified as cells with stem cell features and with neurogenic potential, did express neither endogenous DCX nor the dsRed2 reporter. However, and surprisingly, we identified a perivascular glial cell type expressing the dsRed2 reporter, enmeshed with the glia/stem cell marker GFAP and colocalizing with the

  14. Environmental Enrichment Increases Progenitor Cell Survival in the Dentate Gyrus following Lateral Fluid Percussion Injury

    OpenAIRE

    2005-01-01

    Neurons in the hilus of the dentate gyrus are lost following a lateral fluid percussion injury. Environmental enrichment is known to increase neurogenesis in the dentate in intact rats, suggesting that it might also do so following fluid percussion injury, and potentially provide replacements for lost neurons. We report that 1 hour of daily environmental enrichment for 3 weeks increased the number of progenitor cells in the dentate following fluid percussion injury, but only on the ipsilesion...

  15. 慢性砷中毒对小鼠齿状回GFAP表达的影响%Effects of chronic arsenic poisoning on GFAP expression in the dentate gyms of adult mice

    Institute of Scientific and Technical Information of China (English)

    康朝胜; 孙宝飞; 余资江; 李玉飞

    2011-01-01

    Objective To investigate activation of glial fibrillary acidic protein (GFAP) in the dentate gyrus of adult mice after chronic arsenic poisoning. Methods 80 healthy adult Kunming mice, weighing 20-22g, were divided into four groups: the normal control group, the low-dose group, the medium-dose group and the high-dose group ( 10 males and 10 females in each group). Mice in the four groups were respectively fed with distilled water, 1/5 LD50, 1/10 LD50 and 1/40 LD50 AS2O3 for 3 months, and the dosage was adjusted according to changes of weight. Then ability of learning and memory was tested by a Y-maze, and expression of the GFAP protein in the dentate gyrus by Western blot and immunohistochemistry. Results Ability of learning and memory in the high-dose group was significantly lower than that in the normal control group ( P < 0.05 ). Immunohistochemical results showed that the number of GFAP-positive cells in the dentate gyrus was significantly more increased in the dose groups compared with the normal control group(P<0.01 ), and the average optical density was also increased (P <0.01 ). Western blot results showed the GFAP protein content increased with the dosage increasing (P <0.01 ). Conclusion Chronic arsenic poisoning might damage ability of learning and memory in mice, which may be related to proliferation of astroeytes and expression of GFAP in the dentate gyrus.%目的 研究砷中毒后小鼠齿状回胶质原纤维酸性蛋白(GFAP)的变化.方法 选取健康成年昆明小鼠80只,雌雄各半,分为对照组及慢性砷中毒高、中、低剂量组,每组20只,分别以蒸馏水、1/5 LD50、1/10 LD50、1/40LD50 As2O3连续灌胃3个月,根据其体质量变化随时调整用药剂量,采用Y-电迷宫检测各组小鼠学习记忆行为,采用免疫组织化学和蛋白印迹技术检测不同浓度砷中毒对小鼠齿状回部位GFAP表达的影响.结果 与正常对照组比较,高剂量砷中毒组学习、记忆Y-迷

  16. Redistribution of ionotropic glutamate receptors detected by laser microdissection of the rat dentate gyrus 48 h following LTP induction in vivo.

    Directory of Open Access Journals (Sweden)

    Jeremy T T Kennard

    Full Text Available The persistence and input specificity of long-term potentiation (LTP make it attractive as a mechanism of information storage. In its initial phase, both in vivo and in vitro studies have shown that LTP is associated with increased membrane localization of AMPA receptor subunits, but the molecular basis of LTP maintenance over the long-term is still unclear. We have previously shown that expression of AMPA and NMDA receptor subunits is elevated in whole homogenates prepared from dentate gyrus 48 h after LTP induction in vivo. In the present study, we utilized laser microdissection (LMD techniques to determine whether AMPA and NMDA receptor upregulation occurs specifically in the stimulated regions of the dentate gyrus dendritic arbor. Receptor proteins GluN1, GluA1 and GluA2, as well as postsynaptic density protein of 95 kDa and tubulin were detected by Western blot analysis in microdissected samples. Gradients of expression were observed for GluN1 and GluA2, decreasing from the inner to the outer zones of the molecular layer, and were independent of LTP. When induced at medial perforant path synapses, LTP was associated with an apparent specific redistribution of GluA1 and GluN1 to the middle molecular layer that contains these synapses. These data indicate that glutamate receptor proteins are delivered specifically to dendritic regions possessing LTP-expressing synapses, and that these changes are preserved for at least 48 h.

  17. Differential roles of orexin receptors within the dentate gyrus in stress- and drug priming-induced reinstatement of conditioned place preference in rats.

    Science.gov (United States)

    Ebrahimian, Fereshte; Naghavi, Farzaneh Sadat; Yazdi, Fatemeh; Sadeghzadeh, Fatemeh; Taslimi, Zahra; Haghparast, Abbas

    2016-02-01

    Orexins are hypothalamic peptides involved in the modulation of the feeding, arousal, reward function, learning, and memory; nevertheless, the role of orexins in stress and relapse are largely unclear. Therefore, in the present study, the reinstatement model were used to examine the effects of intradentate gyrus (DG) administration of SB334867 as an orexin-1 receptor antagonist and TCS OX2 29, as an orexin-2 receptor antagonist on drug priming- and forced swim stress (FSS)-induced reinstatement of morphine. One-hundred and 44 adult male albino Wistar rats weighing 200 g-280 g were bilaterally implanted by cannulas into the DG. For induction of conditioned place preference (CPP), subcutaneous (sc) injection of morphine (5 mg/kg) was used daily during a 3-day conditioning phase. Then, the conditioning score (conditional stimulus [CS]) was calculated. After a 24 hr "off" period following achievement of extinction criterion, rats were tested for drug priming-induced reinstatement by priming dose of morphine (1 mg/kg, sc) and for FSS-induced reinstatement 10 min after FSS. In the next experiments, animals received different doses of intra-DG administration of SB334867 and TCS OX2 29 (3, 10, and 30 μg/0.5 μl 12% DMSO per side), bilaterally and were subsequently tested for morphine priming- and FSS-induced reinstatement. Our findings indicated that the FSS-induced the reinstatement of seeking behaviors. Furthermore, intra-DG administration of orexin-1 and orexin-2 receptor antagonists attenuated drug priming-induced reinstatement dose-dependently. However, they have trivial role in FSS-induced reinstatement. It is concluded that drug priming-induced reinstatement may be mediated, at least in part, by stimulation of orexin receptors in the DG.

  18. Aquisição de uma tarefa temporal (DRL por ratos submetidos a lesão seletiva do giro denteado The acquisition of a temporal task (DRL by dentate gyrus-selective colchicine lesioned rats

    Directory of Open Access Journals (Sweden)

    José Lino Oliveira Bueno

    2006-01-01

    Full Text Available A lesão seletiva do giro denteado (DG reduz a eficiência do desempenho de ratos treinados pré-operatoriamente em um esquema de reforçamento diferencial de baixas taxas (DRL; embora os animais lesados sejam capazes de suprimir a resposta de pressão na barra por determinado intervalo de tempo após a resposta anterior, eles subestimam esse intervalo, resultando em um desempenho menos eficiente. Como os animais tinham recebido treinamento pré-operatório, não ficou claro se a lesão interfere na aquisição da discriminação temporal. Este estudo avaliou o efeito da lesão do DG na aquisição de uma tarefa de DRL-20 s. Ratos foram submetidos à neurocirurgia e então ao treino na tarefa de DRL-20 s. Os resultados mostraram que embora os animais lesados se beneficiem do treinamento na tarefa, sua aquisição não é tão eficiente quanto a exibida pelos animais controle. Os resultados sugerem ainda que a lesão do giro denteado interfere na acuidade da discriminação temporal.Previous studies have shown that dentate gyrus damage render rats less efficient than sham-operated controls in the performance of a differential reinforcement of low rates of responding (DRL-20 s task acquired prior to the lesion; even though the lesioned rats were able to postpone their responses after a previous bar press, they seem to underestimate time relative to sham-operated controls, which interferes with their performance. This study investigated the effects of multiplesite, intradentate, colchicine injections on the acquisition and performance of a DRL-20 s task in rats not exposed to preoperatory training, i.e., trained after the lesion. Results showed that the lesioned rats improved along repetitive training in the DRL-20 s task; however, relative to the sham-operated controls, their acquisition rate was slower and the level of proficiency achieved was poorer, indicating that damage to the dentate gyrus interferes with temporal discrimination.

  19. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Directory of Open Access Journals (Sweden)

    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  20. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Science.gov (United States)

    Zhang, Kuan; Zhou, Yanzhao; Zhao, Tong; Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

    Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  1. Adolescent social isolation influences cognitive function in adult rats

    Institute of Scientific and Technical Information of China (English)

    Feng Shao; Xiao Han; Shuang Shao; Weiwen Wang

    2013-01-01

    Adolescence is a critical period for neurodevelopment. Evidence from animal studies suggests that isolated rearing can exert negative effects on behavioral and brain development. The present study aimed to investigate the effects of adolescent social isolation on latent inhibition and brain-derived neurotrophic factor levels in the forebrain of adult rats. Male Wistar rats were randomly divided into adolescent isolation (isolated housing, 38–51 days of age) and social groups. Latent inhibition was tested at adulthood. Brain-derived neurotrophic factor levels were measured in the medial prefrontal cortex and nucleus accumbens by an enzyme-linked immunosorbent assay. Adolescent social isolation impaired latent inhibition and increased brain-derived neurotrophic factor levels in the medial prefrontal cortex of young adult rats. These data suggest that adolescent social isolation has a profound effect on cognitive function and neurotrophin levels in adult rats and may be used as an animal model of neurodevelopmental disorders.

  2. Interleukin-1 mediates long-term hippocampal dentate granule cell loss following postnatal viral infection.

    Science.gov (United States)

    Orr, Anna G; Sharma, Anup; Binder, Nikolaus B; Miller, Andrew H; Pearce, Bradley D

    2010-05-01

    Viral infections of the developing CNS can cause long-term neuropathological sequela through undefined mechanisms. Proinflammatory cytokines such as IL-1beta have gained attention in mediating neurodegeneration in corticohippocampal structures due to a variety of insults in adults, though there is less information on the developing brain. Little is known concerning the spatial-temporal pattern of IL-1beta induction in the developing hippocampus following live virus infection, and there are few studies addressing the long-term consequences of this cytokine induction. We report that infection of rats with lymphocytic choriomeningitis virus on postnatal day 4 induces IL-1beta protein in select regions of the hippocampus on 6, 15, 21, and 45 days after infection. This infection resulted in a 71% reduction of dentate granule cell neurons by the time the rats reached mid-adulthood. We further investigated the causative role of IL-1 in this dentate granule cell loss by blocking IL-1 activity using an IL-1ra-expressing adenoviral vector administered at the time of infection. Blockade of IL-1 abrogated the infection-associated neuron loss in this vivo model. Considering that IL-1 can be triggered by multiple perinatal insults, our findings suggest that early therapy with anti-inflammatory agents that block IL-1 may be effective for reducing adulthood neuropathology.

  3. Expression of mRNA coding voltage - gated sodium channel α-subunit in spontaneously epileptic rat

    Institute of Scientific and Technical Information of China (English)

    DUWa; CAIJi-Qun

    2004-01-01

    OBJECTIVE Subtypes Ⅰ,Ⅱ and Ⅲ of sodium channel α- subunit mRNA were analyzed in adult rat brain of spontaneously epileptic rats, and investigated the relationship between sodium channel expression and epilepsy. METHODS Tissue samples were microdissected from occipital neocortex, CA1 and CA3 hippocampus areas and dentate gyms, observe

  4. The effect of acute swim stress and training in the water maze on hippocampal synaptic activity as well as plasticity in the dentate gyrus of freely moving rats: revisiting swim-induced LTP reinforcement.

    Science.gov (United States)

    Tabassum, Heena; Frey, Julietta U

    2013-12-01

    Hippocampal long-term potentiation (LTP) is a cellular model of learning and memory. An early form of LTP (E-LTP) can be reinforced into its late form (L-LTP) by various behavioral interactions within a specific time window ("behavioral LTP-reinforcement"). Depending on the type and procedure used, various studies have shown that stress differentially affects synaptic plasticity. Under low stress, such as novelty detection or mild foot shocks, E-LTP can be transformed into L-LTP in the rat dentate gyrus (DG). A reinforcing effect of a 2-min swim, however, has only been shown in (Korz and Frey (2003) J Neurosci 23:7281-7287; Korz and Frey (2005) J Neurosci 25:7393-7400; Ahmed et al. (2006) J Neurosci 26:3951-3958; Sajikumar et al., (2007) J Physiol 584.2:389-400) so far. We have reinvestigated these studies using the same as well as an improved recording technique which allowed the recording of field excitatory postsynaptic potentials (fEPSP) and the population spike amplitude (PSA) at their places of generation in freely moving rats. We show that acute swim stress led to a long-term depression (LTD) in baseline values of PSA and partially fEPSP. In contrast to earlier studies a LTP-reinforcement by swimming could never be reproduced. Our results indicate that 2-min swim stress influenced synaptic potentials as well as E-LTP negatively.

  5. Expression of Caspase-3 in Dentate Gyrus of Adult Mice with Chronic Arsenic Poisoning%慢性砷中毒对小鼠齿状回caspase-3表达的影响

    Institute of Scientific and Technical Information of China (English)

    孙宝飞; 康朝胜; 余资江; 李玉飞

    2011-01-01

    目的 观察慢性砷中毒对成年小鼠齿状回神经元的形态学影响,探讨慢性砷中毒对成年小鼠脑部的神经毒性机制.方法 选取健康成年昆明小鼠80只,雌雄各半,分为对照组、高、中、低剂量砷染毒组,每组20只,高、中、低剂量砷染毒组分别以As03的1/5、1/10、1/40 LD50(9、4.5、1.1 mg/kg)灌胃染毒,对照组以蒸馏水灌胃,连续3个月.利用免疫组织化学和蛋白印迹技术观察小鼠齿状回部位神经元半胱氨酸蛋白水解酶-3(caspase-3)蛋白的表达.结果 免疫组化染色显示,与正常对照组比较,砷染毒组小鼠齿状回caspase-3阳性细胞明显增多(P<0.01),阳性反应产物平均光密度增高(P<0.01),同时蛋白印迹结果显示随砷中毒剂量的增加,小鼠齿状回caspase-3蛋白含量随之增加(P<0.01),各剂量组雌雄间各数据差异无统计学意义(P>0.05).结论 慢性砷中毒导致脑齿状回神经元细胞凋亡可能与齿状回细胞caspase-3增加有关,同时脑细胞caspase-3随砷浓度增加而增高.%Objective To investigate the effects of chronic arsenic exposure at different doses on dentate gyrus neurons in adult mice. Methods Eighty healthy adult Kunming mice, 20-22 g, were randomly divided into four groups: normal control group, low-dose group, moderate dose group and high dose group, 20 in each (10 males and 10 females in each group), each group was fed respectively with distilled water, 1/5 LD50, 1/10 LD50 and 1/40 LD50 As203 for 3 consecutive months, and adjusting the dose according to their weight changes. The content of arsenic in brain was determined. The expression of caspase-3 in dentate gyrus neurons was detected by western blotting and immunohistochemistry and analyzed by morphology methods. Results Compared with normal control group, groups of arsenic poisoning had been the main changes: caspase-3 immunohistochemical staining positive cells increased significantly (P0.05). Conclusion The obvious up

  6. Regional differences in GABAergic modulation for TEA-induced synaptic plasticity in rat hippocampal CA1, CA3 and dentate gyrus.

    Science.gov (United States)

    Suzuki, Etsuko; Okada, Takashi

    2007-10-01

    Tetraethylammonium (TEA), a K(+)-channel blocker, reportedly induces long-term potentiation (LTP) of hippocampal CA1 synaptic responses, but at CA3 and the dentate gyrus (DG), the characteristics of TEA-induced plasticity and modulation by inhibitory interneurons remain unclear. This study recorded field EPSPs from CA1, CA3 and DG to examine the involvement of GABAergic modulation in TEA-induced synaptic plasticity for each region. In Schaffer collateral-CA1 synapses and associational fiber (AF)-CA3 synapses, bath application of TEA-induced LTP in the presence and absence of picrotoxin (PTX), a GABA(A) receptor blocker, whereas TEA-induced LTP at mossy fiber (MF)-CA3 synapses was detected only in the absence of GABA(A) receptor blockers. MF-CA3 LTP showed sensitivity to Ni(2+), but not to nifedipine. In DG, synaptic plasticity was modulated by GABAergic inputs, but characteristics differed between the afferent lateral perforant path (LPP) and medial perforant path (MPP). LPP-DG synapses showed TEA-induced LTP during PTX application, whereas at MPP-DG synapses, TEA-induced long-term depression (LTD) was seen in the absence of PTX. This series of results demonstrates that TEA-induced DG and CA3 plasticity displays afferent specificity and is exposed to GABAergic modulation in an opposite manner.

  7. The effect of immature adult-born dentate granule cells on hyponeophagial behavior is related to their roles in learning and memory

    Directory of Open Access Journals (Sweden)

    Wei eDeng

    2015-03-01

    Full Text Available The neurogenesis hypothesis of depression is based on the correlation between the rate of adult hippocampal neurogenesis and the affective status of rodents. However, studies investigating the role of neurogenesis in the causation of mood regulation have reported inconsistent results. Here, we explored whether the affective state can be affected differentially by adult-born neurons with distinctive physiological characteristics at different maturation stages. We revealed that reducing the immature newborn neuron population had no effect on anxiety- or depression-like behaviors in an array of tests; however, it enhanced hyponeophagia in a novelty suppressed feeding test, but only when the novel environment was drastically different from the home cage. We further demonstrated that reducing the immature newborn neuron population led to delayed habituation to a novel environment and impaired contextual learning. Hence, rather than being directly involved in mood regulation, our studies raise the possibility that adult neurogenesis may influence hyponeophagia through its role in mnemonic processing.

  8. Hyperprolactinemia affects spermiogenesis in adult male rats.

    Science.gov (United States)

    Aleem, M; Choudhari, J; Padwal, V; Balasinor, N; Parte, P; Gill-Sharma, M K

    2005-01-01

    The mechanisms underlying the antifertility effects of hyperprolactinemia have yet to be established in an appropriate experimental model. Hyperprolactinemia is a known side effect of fluphenazine, a broad spectrum, long-acting phenothiazine known to be dopamine type-D2 receptor antagonist. In our earlier study in adult male rats, we reported that fluphenazine at a dose of 3 mg/kg/day suppressed serum FSH but not testosterone (T) through increasing dopamine (DA) metabolism in the pituitary gland, within 60 days. Fluphenazine treatment affected sperm quality and male rats treated with fluphenazine sired fewer litters. The effects of fluphenazine-induced hyperprolactinemia on sperm quality appeared to be related to reduced FSH. We now report that FSH suppression enhanced the uptake of acridine orange (AO), a DNA intercalating, fluorescent dye by the fluphenazine-treated caput epididymal sperms with concomitant reduction in the uptake of thiol-specific monobromobimane (mBBr) fluorescent dye in vitro, suggesting greater accessibility of DNA intercalating dye to sperm chromatin and reduction in free sperm protein thiols. The concomitant increase in AO and decrease in mBBr fluorescence was suggestive of loose chromatin packaging in caput epididymal sperms after treatment with fluphenazine at 3 mg/kg/day for 60 days. The suppression in levels of protamine (P1) in caput epididymal sperms suggested that chromatin hypocompaction was due to reduced deposition of protamines in sperm chromatin. Reduction in testicular levels of cyclic adenosyl 3', 5' monophosphate response element modulator (CREMtau) and P1 further suggested that reduced deposition was indeed due to reduced synthesis. The concomitant reduction in testicular levels of transition protein 1 (TP1) and transition protein 2 (TP2) also suggested that hypoprotamination was due to reduced synthesis of these proteins crucial for facilitating P1 deposition. The effect appeared to have occurred at the level of translation

  9. Dobutamine stress echocardiography in healthy adult male rats

    OpenAIRE

    Couet Jacques; Roussel Élise; Drolet Marie-Claude; Lachance Dominic; Plante Eric; Arsenault Marie

    2005-01-01

    Abstract Background Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intra...

  10. Hypertension after bilateral kidney irradiation in young and adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-09-01

    The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension.

  11. Statins Increase Neurogenesis in the Dentate Gyrus, Reduce Delayed Neuronal Death in the Hippocampal CA3 Region, and Improve Spatial Learning in Rat after Traumatic Brain Injury

    OpenAIRE

    Lu, Dunyue; Qu, Changsheng; Goussev, Anton; Jiang, Hao; Lu, Chang; Schallert, Timothy; Mahmood, Asim; Chen, Jieli; Li, Yi; Chopp, Michael

    2007-01-01

    Traumatic brain injury (TBI) remains a major public health problem globally. Presently, there is no way to restore cognitive deficits caused by TBI. In this study, we seek to evaluate the effect of statins (simvastatin and atorvastatin) on the spatial learning and neurogenesis in rats subjected to controlled cortical impact. Rats were treated with atorvastatin and simvastatin 1 day after TBI and daily for 14 days. Morris water maze tests were performed during weeks 2 and 5 after TBI. Bromodeo...

  12. Early natural stimulation through environmental enrichment accelerates neuronal development in the mouse dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Na Liu

    Full Text Available The dentate gyrus is the primary afferent into the hippocampal formation, with important functions in learning and memory. Granule cells, the principle neuronal type in the dentate gyrus, are mostly formed postnatally, in a process that continues into adulthood. External stimuli, including environmental enrichment, voluntary exercise and learning, have been shown to significantly accelerate the generation and maturation of dentate granule cells in adult rodents. Whether, and to what extent, such environmental stimuli regulate the development and maturation of dentate granule cells during early postnatal development is largely unknown. Furthermore, whether natural stimuli affect the synaptic properties of granule cells had been investigated neither in newborn neurons of the adult nor during early development. To examine the effect of natural sensory stimulation on the dentate gyrus, we reared newborn mice in an enriched environment (EE. Using immunohistochemistry, we showed that dentate granule cells from EE-reared mice exhibited earlier morphological maturation, manifested as faster peaking of doublecortin expression and elevated expression of mature neuronal markers (including NeuN, calbindin and MAP2 at the end of the second postnatal week. Also at the end of the second postnatal week, we found increased density of dendritic spines across the entire dentate gyrus, together with elevated levels of postsynaptic scaffold (post-synaptic density 95 and receptor proteins (GluR2 and GABA(ARγ2 of excitatory and inhibitory synapses. Furthermore, dentate granule cells of P14 EE-reared mice had lower input resistances and increased glutamatergic and GABAergic synaptic inputs. Together, our results demonstrate that EE-rearing promotes morphological and electrophysiological maturation of dentate granule cells, underscoring the importance of natural environmental stimulation on development of the dentate gyrus.

  13. The impact of chronic stress on neurogenesis in hippocampal dentate gyrus in rats%慢性应激对大鼠海马齿状回神经发生的影响

    Institute of Scientific and Technical Information of China (English)

    吴萍

    2012-01-01

    Objective:To investigate the impact of chronic stress on proliferation and maturation of newborn nerve cells in hippocampal dentate gyrus in rats. Methods: The chronic stress rat models were established by chronic bondage method and evaluated their spatial learning and memory abilities by the Morris water maze. Furthermore, immunofluorescence staining and confocal microscopy were used to observe the changes of DCX-positive cell number and the length of dendrites in the DC region of dentate gyrus after chronic stress. Results: The escape latency in model group (48. 13 ±4. 7) second was significantly longer than that in control group (13. 64 ±3. 55) second. The number of platform crossing was significantly less in model group ( 1. 33 ±0. 09) than in the control group (2.75 ±0. 16) (both P<0.05). Compared with control group (37.89 ±9.4) .model group (37. 89 ±9.4) had significantly decreased DCX positive cell number in DC region in hippocampal denate gyrus. The total length of dendrites of DCX positive cells in DC region in hippocampal denate gyrus was significantly shorter in model group ( 168. 44 ±9. 46) μm than in control group (235. 67 ± 19. 57) μm ( both P < 0.05). Conclusion:Chronic stress could inhibit the proliferation and maturation of newborn nerve cells in rats, which might affect the learning and memory abilities of rats.%目的:探讨慢性应激对大鼠海马齿状回(DG)新生神经细胞增殖及成熟的影响.方法:用慢性束缚法制作大鼠慢性应激模型,利用Morris水迷宫试验对其进行空间学习记忆功能的评价,并通过免疫荧光染色及共聚焦显微镜成像技术观察慢性应激后海马DG区DCX阳性细胞的数量及树突长度的变化.结果:模型组大鼠在水迷宫实验中的逃避潜伏期为(48.13±4.7)s,明显长于对照组的(13.64±3.55)s;模型组大鼠在限定时间内穿越平台的次数为(1.33 ±0.09)次,明显少于对照组的(2.75±0.16)次,差异均有统计学意义(均P <0

  14. Differential dendritic targeting of AMPA receptor subunit mRNAs in adult rat hippocampal principal neurons and interneurons.

    Science.gov (United States)

    Cox, David J; Racca, Claudia

    2013-06-15

    In hippocampal neurons, AMPA receptors (AMPARs) mediate fast excitatory postsynaptic responses at glutamatergic synapses, and are involved in various forms of synaptic plasticity. Dendritic local protein synthesis of selected AMPAR subunit mRNAs is considered an additional mechanism to independently and rapidly control the strength of individual synapses. We have used fluorescent in situ hybridization and immunocytochemistry to analyze the localization of AMPAR subunit (GluA1-4) mRNAs and their relationship with the translation machinery in principal cells and interneurons of the adult rat hippocampus. The mRNAs encoding all four AMPAR subunits were detected in the somata and dendrites of CA3 and CA1 pyramidal cells and those of six classes of CA1 γ-aminobutyric acid (GABA)ergic interneurons. GluA1-4 subunit mRNAs were highly localized to the apical dendrites of pyramidal cells, whereas in interneurons they were present in multiple dendrites. In contrast, in the dentate gyrus, GluA1-4 subunit mRNAs were virtually restricted to the somata and were absent from the dendrites of granule cells. These different regional and cell type-specific labeling patterns also correlated with the localization of markers for components of the protein synthesis machinery. Our results support the local translation of GluA1-4 mRNAs in dendrites of hippocampal pyramidal cells and CA1 interneurons but not in granule cells of the dentate gyrus. Furthermore, the regional and cell type-specific differences we observed suggest that each cell type uses distinct ways of regulating the local translation of AMPAR subunits.

  15. Influx mechanisms in the embryonic and adult rat choroid plexus

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and a...

  16. Oscillatory dynamics in the hippocampus support dentate gyrus–CA3 coupling.

    OpenAIRE

    Akam T; Oren I; Mantoan L; Ferenczi E; Kullmann DM.

    2012-01-01

    Gamma oscillations in the dentate gyrus and hippocampal CA3 show variable coherence in vivo, but the mechanisms and relevance for information flow are unknown. We found that carbachol-induced oscillations in rat CA3 have biphasic phase-response curves, consistent with the ability to couple with oscillations in afferent projections. Differences in response to stimulation of either the intrinsic feedback circuit or the dentate gyrus were well described by varying an impulse vector in a two-dime...

  17. Breaches of the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies.

    Science.gov (United States)

    Li, Jing; Yu, Miao; Feng, Gang; Hu, Huaiyu; Li, Xiaofeng

    2011-11-07

    A subset of congenital muscular dystrophies (CMDs) has central nervous system manifestations. There are good mouse models for these CMDs that include POMGnT1 knockout, POMT2 knockout and Large(myd) mice with all exhibiting defects in dentate gyrus. It is not known how the abnormal dentate gyrus is formed during the development. In this study, we conducted a detailed morphological examination of the dentate gyrus in adult and newborn POMGnT1 knockout, POMT2 knockout, and Large(myd) mice by immunofluorescence staining and electron microscopic analyses. We observed that the pial basement membrane overlying the dentate gyrus was disrupted and there was ectopia of granule cell precursors through the breached pial basement membrane. Besides these, the knockout dentate gyrus exhibited reactive gliosis in these mouse models. Thus, breaches in the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies.

  18. Effect of a antisense oligonucleotide to noggin on the expression of nestin and GFAP in the hippocampus of adult rats%反义Noggin基因对成年大鼠海马内Nestin及GFAP表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐海伟; 范晓棠

    2005-01-01

    目的探讨Noggin基因对成年大鼠海马内Nestin及GFAP表达的影响.方法反义寡核苷酸技术封闭内源性Noggin基因的表达,免疫组化法检测成年大鼠海马内Nestin与GFAP的表达.结果侧脑室连续4 d注射Noggin基因的反义寡核苷酸后,可见海马齿状回(dentate gyrus,DG)内Nestin阳性细胞数与GFAP阳性细胞数较对照组显著增加;室下区GFAP阳性细胞数亦明显增加.结论Noggin对成年海马干细胞的分化有重要作用,内源性Noggin基因的表达可使神经干细胞向神经元方向分化.%Objective To examine the role of noggin on the expression of nestin and glial fibrillary acidic protein (GFAP) in the hippocampus of adult rats. Methods Antisense oligodeoxynucleotide (ASODN) technique was employed to inhibit endogenous noggin expression and immunohistochemistry was used to detect the expressions of Nestin and GFAP in the hippocampus of adult rats. Results It was observed that the number of nestin and GFAP immunoreactive cells in the dentate gyrus (DG) of hippocampus was increased in adult rats treated with antisense oligodeoxynucleotide to noggin. Moreover, the number of GFAP immunoreactive cells was increased in the subventricular zone of the rats treated with antisense oligodeoxynucleotide to noggin. Conclusion The results in the present study indicates that noggin may play a role in the differentiation of neural stem cells in the adult hippocampus, and it promotes the differentiation of neural stem cells in the DG to neuronal fate.

  19. Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat

    Energy Technology Data Exchange (ETDEWEB)

    Oleskevich, S.; Descarries, L.; Lacaille, J.C. (Universite de Montreal, Quebec (Canada))

    1989-11-01

    A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus.

  20. Ultrasonic Vocalizations by Adult Rats (Rattus norvegicus)

    Science.gov (United States)

    1991-12-01

    begun. Diazepam , chlordiazepoxide , morphine, or naloxone was administered I.P. prior to placing the rat in the tailshock apparatus. Four different...by chlordiazepoxide and diazepam . Drug Dev. Res., 5, 185-193 (1985). Gardner, C.R., and Budhram, P. Effects of agents which interact with central... diazepam , and chlorpromazine, attenuate these vocalizations. Recent work by Kaltwasser (1990) examined the occurrence of vocalizations in response to

  1. Evolution of the mammalian dentate gyrus.

    Science.gov (United States)

    Hevner, Robert F

    2016-02-15

    The dentate gyrus (DG), a part of the hippocampal formation, has important functions in learning, memory, and adult neurogenesis. Compared with homologous areas in sauropsids (birds and reptiles), the mammalian DG is larger and exhibits qualitatively different phenotypes: 1) folded (C- or V-shaped) granule neuron layer, concave toward the hilus and delimited by a hippocampal fissure; 2) nonperiventricular adult neurogenesis; and 3) prolonged ontogeny, involving extensive abventricular (basal) migration and proliferation of neural stem and progenitor cells (NSPCs). Although gaps remain, available data indicate that these DG traits are present in all orders of mammals, including monotremes and marsupials. The exception is Cetacea (whales, dolphins, and porpoises), in which DG size, convolution, and adult neurogenesis have undergone evolutionary regression. Parsimony suggests that increased growth and convolution of the DG arose in stem mammals concurrently with nonperiventricular adult hippocampal neurogenesis and basal migration of NSPCs during development. These traits could all result from an evolutionary change that enhanced radial migration of NSPCs out of the periventricular zones, possibly by epithelial-mesenchymal transition, to colonize and maintain nonperiventricular proliferative niches. In turn, increased NSPC migration and clonal expansion might be a consequence of growth in the cortical hem (medial patterning center), which produces morphogens such as Wnt3a, generates Cajal-Retzius neurons, and is regulated by Lhx2. Finally, correlations between DG convolution and neocortical gyrification (or capacity for gyrification) suggest that enhanced abventricular migration and proliferation of NSPCs played a transformative role in growth and folding of neocortex as well as archicortex.

  2. Fast, potent pharmacological expansion of endogenous hes3+/sox2+ cells in the adult mouse and rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Simone Pacioni

    Full Text Available The adult hippocampus is involved in learning and memory. As a consequence, it is a brain region of remarkable plasticity. This plasticity exhibits itself both as cellular changes and neurogenesis. For neurogenesis to occur, a population of local stem cells and progenitor cells is maintained in the adult brain and these are able to proliferate and differentiate into neurons which contribute to the hippocampal circuitry. There is much interest in understanding the role of immature cells in the hippocampus, in relation to learning and memory. Methods and mechanisms that increase the numbers of these cells will be valuable in this research field. We show here that single injections of soluble factors into the lateral ventricle of adult rats and mice induces the rapid (within one week increase in the number of putative stem cells/progenitor cells in the hippocampus. The established progenitor marker Sox2 together with the more recently established marker Hes3, were used to quantify the manipulation of the Sox2/Hes3 double-positive cell population. We report that in both adult rodent species, Sox2+/Hes3+ cell numbers can be increased within one week. The most prominent increase was observed in the hilus of the dentate gyrus. This study presents a fast, pharmacological method to manipulate the numbers of endogenous putative stem cells/progenitor cells. This method may be easily modified to alter the degree of activation (e.g. by the use of osmotic pumps for delivery, or by repeat injections through implanted cannulas, in order to be best adapted to different paradigms of research (neurodegenerative disease, neuroprotection, learning, memory, plasticity, etc.

  3. A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three-dimensional ultrastructural study

    DEFF Research Database (Denmark)

    Popov, Victor I; Medvedev, Nikolay I; Kraev, Igor V

    2008-01-01

    The FGL peptide is a neural cell adhesion molecule (NCAM) mimetic comprising a 15-amino-acid-long sequence of the FG loop region of the second fibronectin type III module of NCAM. It corresponds to the binding site of NCAM for the fibroblast growth factor receptor 1. FGL improves cognitive function...... through enhancement of synaptic function. We examined the effect of FGL on synaptic and dendritic structure in the brains of aged (22-month-old) rats that were injected subcutaneously (8 mg/kg) at 2-day intervals until 19 days after the start of the experiment. Animals were perfused with fixative, brains...... removed and coronal sections cut at 50 microm. The hippocampal volume was measured, tissue embedded and ultrathin sections viewed in a JEOL 1010 electron microscope. Analyses were made of synaptic and dendritic parameters following three-dimensional reconstruction via images from a series of approximately...

  4. Pre- and Posttreatment With Edaravone Protects CA1 Hippocampus and Enhances Neurogenesis in the Subgranular Zone of Dentate Gyrus After Transient Global Cerebral Ischemia in Rats

    Directory of Open Access Journals (Sweden)

    Shan Lei

    2014-11-01

    Full Text Available Edaravone is clinically used for treatment of patients with acute cerebral infarction. However, the effect of double application of edaravone on neurogenesis in the hippocampus following ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of edaravone had any effect on neural stem/progenitor cells (NSPCs in the subgranular zone of hippocampus in a rat model of transient global cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups: sham-operated (n = 15, control (n = 15, and edaravone-treated (n = 15 groups. Newly generated cells were labeled by 5-bromo-2-deoxyuridine. Immunohistochemistry was used to detect neurogenesis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling was used to detect cell apoptosis. Reactive oxygen species (ROS were detected by 2,7-dichlorofluorescien diacetate assay in NSPCs in vitro. Hypoxia-inducible factor-1α (HIF-1α and cleaved caspase-3 proteins were quantified by western blot analysis. Treatment with edaravone significantly increased the number of NSPCs and newly generated neurons in the subgranular zone (p < .05. Treatment with edaravone also decreased apoptosis of NSPCs (p < .01. Furthermore, treatment with edaravone significantly decreased ROS generation and inhibited HIF-1α and cleaved caspase-3 protein expressions. These findings indicate that pre- and posttreatment with edaravone enhances neurogenesis by protecting NSPCs from apoptosis in the hippocampus, which is probably mediated by decreasing ROS generation and inhibiting protein expressions of HIF-1α and cleaved caspase-3 after cerebral ischemia.

  5. Proliferation and differentiation of neural stem cells in hippocampus dentate gyrus in aged rats after intracerebral hemorrhage%老年大鼠脑出血后海马齿状回神经干细胞的增殖与分化

    Institute of Scientific and Technical Information of China (English)

    文玉军; 王登科; 孙征; 刘海洋; 张莲香; 王效军; 秦毅

    2011-01-01

    Objective To investigate proliferation and differentiation of neural stem cells (NSCs) in the hippocampus dentate gyrus in aged rats after intracerebral hemorrhage ( ICH) , and to explore the variation of NSCs after ICH. Methods ICH models were established by injecting collagenase VH into the brain of aged rats. Proliferating cells were labeled by BrdU through abdominal cavity injection. Immunohistochemical single and double staining with antibodies agaist BrdU, NeuN and GFAP were used to determine proliferation and differentiation of hippocampus dentate gyrus. Results In non-ICH aged rats, BrdU positive cells in hippocampus dentate gyrus were little. After ICH, BrdU positive cells in hippocampus dentate gyrus of aged rats were significantly increased and reached peak after 7d. In non-ICH aged rats, BrdU/NeuN and BrdU/GFAP double positive cells were found in the hippocampus dentate gyrus. After ICH,the quantity of double positive cells increased obviously. Conclusion After ICH,NSCs in hippocampus dentate gyrus of aged rats are activated,which can proliferate and differentiate to neuron or astrocytes.%目的 观察老年大鼠脑出血后海马齿状回神经干细胞(NSCs)的增殖与分化,探讨脑出血后NSCs的变化规律.方法 制作老年大鼠脑出血模型,5-溴脱氧尿核苷(BrdU)腹腔注射标记增殖细胞,用免疫组化法检测大鼠海马齿状回BrdU、神经元核抗原(NeuN)、胶质纤维酸性蛋白(GFAP)阳性细胞数的变化.结果 正常组和假手术组老年大鼠海马齿状回均有少量BrdU阳性细胞,脑出血后大鼠各时间段的BrdU阳性细胞数目均较正常组和假手术组明显增加,7d组达到峰值后逐渐下降,28d组仍高于正常组和假手术组.正常老年大鼠海马齿状回可见少量BrdU/NeuN和BrdU/GFAP双标阳性细胞,脑出血后双标阳性细胞数较正常组明显增加.结论 脑出血后老年大鼠海马齿状回NSCs增殖明显,且可以向神经元和神经胶质细胞分化.

  6. Projection neurons in the cortex and hippocampus: differential effects of chronic khat and ethanol exposure in adult male rats

    Science.gov (United States)

    Alele, Paul E; Matovu, Daniel; Imanirampa, Lawrence; Ajayi, Abayomi M; Kasule, Gyaviira T

    2016-01-01

    Background Recent evidence suggests that many individuals who chew khat recreationally also drink ethanol to offset the stimulating effect of khat. The objective of this study was to describe the separate and interactive effects of chronic ethanol and khat exposure on key projection neurons in the cortex and hippocampus of young adult male rats. Methods Young adult male Sprague Dawley rats were divided into six treatment groups: 2 g/kg khat, 4 g/kg khat, 4 g/kg ethanol, combined khat and ethanol (4 g/kg each), a normal saline control, and an untreated group. Treatments were administered orally for 28 continuous days; brains were then harvested, sectioned, and routine hematoxylin–eosin staining was done. Following photomicrography, ImageJ® software captured data regarding neuron number and size. Results No differences occurred in counts of both granular and pyramidal projection neurons in the motor cortex and all four subfields of the hippocampal formation. Khat dose-dependently increased pyramidal neuron size in the motor cortex and the CA3 region, but had different effects on granular neuron size in the dentate gyrus and the motor cortex. Mean pyramidal neuron size for the ethanol-only treatment was larger than that for the 2 g/kg khat group, and the saline control group, in CA3 and in the motor cortex. Concomitant khat and ethanol increased granular neuron size in the motor cortex, compared to the 2 g/kg khat group, the 4 g/kg khat group, and the 4 g/kg ethanol group. In the CA3 region, the 4 g/kg ethanol group showed a larger mean pyramidal neuron size than the combined khat and ethanol group. Conclusion These results suggest that concomitant khat and ethanol exposure changes granular and pyramidal projection neuron sizes differentially in the motor cortex and hippocampus, compared to the effects of chronic exposure to these two drugs separately.

  7. Contextual fear conditioning differs for infant, adolescent, and adult rats.

    Science.gov (United States)

    Esmorís-Arranz, Francisco J; Méndez, Cástor; Spear, Norman E

    2008-07-01

    Contextual fear conditioning was tested in infant, adolescent, and adult rats in terms of Pavlovian-conditioned suppression. When a discrete auditory-conditioned stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the largely olfactory context, infants and adolescents conditioned to the context with substantial effectiveness, but adult rats did not. When unpaired presentations of the CS and US occurred within the context, contextual fear conditioning was strong for adults, weak for infants, but about as strong for adolescents as when pairings of CS and US occurred in the context. Nonreinforced presentations of either the CS or context markedly reduced contextual fear conditioning in infants, but, in adolescents, CS extinction had no effect on contextual fear conditioning, although context extinction significantly reduced it. Neither CS extinction nor context extinction affected responding to the CS-context compound in infants, suggesting striking discrimination between the compound and its components. Female adolescents showed the same lack of effect of component extinction on response to the compound as infants, but CS extinction reduced responding to the compound in adolescent males, a sex difference seen also in adults. Theoretical implications are discussed for the development of perceptual-cognitive processing and hippocampus role.

  8. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

    Directory of Open Access Journals (Sweden)

    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  9. Effects of lithium on the synaptic plasticity in dentate gyrus region of rat hippocampus%锂对大鼠海马齿状回区神经元突触可塑性的影响

    Institute of Scientific and Technical Information of China (English)

    钟桂生; 阮迪云; 葛少宇; 汪铭; 陈聚涛

    2002-01-01

    AIM To investigate the mechanism of the-rapeutic action of lithium with respect to long-term potentiation(LTP) elicited in dentate gyrus(DG) region of rat hippocampus. METHODS To use conventional extracellular recording technique in hippocampal slices in vitro. RESULTS Lithium was found to reversibly increase excitatory postsynaptic potentials in the DG region of rat hippocampus. Under control conditions, titanic stimulation (100 Hz, 1 s) of medial perforans pathway induced LTP. Acute treatment of low concentration lithium (2, 6 mmol*L-1) did not affect the LTP induced by titanic stimulation, while its higher concentration (10 mmol*L-1) inhibited the amplitude of LTP in the DG region of rat hippocampus. Furthermore, lithium treatment (10 mmol*L-1) decreased paired-pulse facilitation (PPF) measured at 50 ms inter-pulse interval while, at lower concentrations, lithium treatments (2, 6 mmol*L-1) did not affect PPF significantly. We also found that the effects of lithium (10 mmol*L-1) on PPF were different at different [Ca2+]o. CONCLUSIONLithium can inhibit the LTP magnitude in rat hippocampus probably through presynaptic mechanisms. These alterations of neurophysiological responses may be related to the therapeutic action of lithium salts in mania and depression as well as producing side effects of lithium chemotherapy.%目的从齿状回长时程增强效应(LTP)方面研究锂的治疗作用机理.方法细胞外记录离体海马脑片神经元兴奋性突触后电位(EPSP).结果锂可逆地增强EPSP的幅度.高频刺激 (100 Hz, 1 s)对照组大鼠海马穿通纤维,在海马齿状回(DG)区记录的EPSP幅度会持续增高,可以诱导出明显的突触后LTP.若用10 mmol*L-1锂处理大鼠海马脑片,则诱导的LTP幅度明显降低,但低浓度锂(2, 6 mmol*L-1)不影响LTP的幅度;10 mmol*L-1锂明显抑制海马脑片DG区的脉冲间隔(IPI)为50 ms的双脉冲易化效应(PPF),而低浓度锂(2, 6 mmol*L-1)处理则不影响PPF(IPI, 50 ms);在不

  10. Comparative study on influence of fetal bovine serum and serum of adult rat on cultivation of newborn rat neural cells

    Directory of Open Access Journals (Sweden)

    Sukach A. N.

    2014-09-01

    Full Text Available Aim. To study the influence of fetal bovine serum and serum of adult rats on behavior of newborn rat isolated neural cells during their cultivation in vitro. Methods. The isolation of neural cells from neonatal rat brain. The determination of the dynamics of cellular monolayer formation. Immunocytochemical staining of cells for β-tubulin III, nestin and vimentin. Results. It has been determined that the addition of serum of adult rats to the cultivation medium creates more favorable conditions for survival, attachment and spread of differentiated, and proliferation of the stem/progenitor neural cells of newborn rats during cultivation in vitro compared with the fetal bovine serum. Conclusions. Using the serum of adult rats is preferable for the cultivation of isolated neural cells of newborn rats compared with the fetal bovine serum.

  11. Prenatal protein malnutrition alters the proportion but not numbers of parvalbumin-immunoreactive interneurons in the hippocampus of the adult Sprague-Dawley rat.

    Science.gov (United States)

    Lister, James P; Blatt, Gene J; Kemper, Thomas L; Tonkiss, John; DeBassio, William A; Galler, Janina R; Rosene, Douglas L

    2011-07-01

    Prenatal protein malnutrition alters the structure and function of the adult rat hippocampal formation. The current study examines the effect of prenatal protein malnutrition on numbers of parvalbumin-immunoreactive (PV-IR) GABAergic interneurons, which are important for perisomatic inhibition of hippocampal pyramidal neurons. Brain sections from prenatally protein malnourished and normally nourished rats were stained for parvalbumin and PV-IR neurons were quantified using stereology in the dentate gyrus, CA3/2 and CA1 subfields, and the subiculum for both cerebral hemispheres. Results demonstrated that prenatal malnutrition did not affect the number of PV-IR interneurons in the hippocampus. Since prenatal protein malnutrition reduces total neuron numbers in the CA1 subfield (1), this results in an altered ratio of PV-IR interneurons to total neuronal numbers (from 1:22.9 in controls to 1:20.5 in malnourished rats). Additionally, there was no hemispheric asymmetry of either PV-IR neuron numbers or ratio of PV-IR:total neuron numbers.

  12. Behavior modification after inactivation of cerebellar dentate nuclei.

    Science.gov (United States)

    Peterson, Todd C; Villatoro, Lee; Arneson, Tom; Ahuja, Brittany; Voss, Stephanie; Swain, Rodney A

    2012-08-01

    Effort-based decision making occurs when subjects are given a choice between a reward available at a high response cost and a reward available at a low response cost and is altered in individuals with disorders such as autism or particular patterns of brain injury. The current study explored the relationship between effort-based decision making and reinforcement characteristics in the T maze. This was done using both normal animals and animals with bilateral inactivation of the cerebellar dentate nuclei. Rats chose between alternatives in which one arm contained high-density reinforcement (HR) and the other arm contained low-density reinforcement (LR). During training, the HR arm was obstructed and the point at which the animal no longer worked for reinforcement (breaking point) was determined. The cerebellar dentate nuclei were then transiently inactivated and once again breaking points were assessed. The results indicated that inactivation of the dentate nucleus disrupted effort-based decision making. Additionally, altering both the palatability and the magnitude of the reinforcement were assessed in an attempt to reestablish the original preinactivation breaking point. It was hypothesized that an increase in the strength or magnitude of the reinforcement would promote an increase in the breaking point of the animal even when the cerebellum was inactivated. The results indicated that with both strategies animals effectively reestablished original breaking points. The results of this study will inform the current literature regarding the modification of behavior after brain injury and further the understanding of the behavioral deficits associated with cerebellar dysfunction.

  13. Amygdala kindling alters protein kinase C activity in dentate gyrus.

    Science.gov (United States)

    Chen, S J; Desai, M A; Klann, E; Winder, D G; Sweatt, J D; Conn, P J

    1992-11-01

    Kindling is a use-dependent form of synaptic plasticity and a widely used model of epilepsy. Although kindling has been widely studied, the molecular mechanisms underlying induction of this phenomenon are not well understood. We determined the effect of amygdala kindling on protein kinase C (PKC) activity in various regions of rat brain. Kindling stimulation markedly elevated basal (Ca(2+)-independent) and Ca(2+)-stimulated phosphorylation of an endogenous PKC substrate (which we have termed P17) in homogenates of dentate gyrus, assayed 2 h after kindling stimulation. The increase in P17 phosphorylation appeared to be due at least in part to persistent PKC activation, as basal PKC activity assayed in vitro using an exogenous peptide substrate was increased in kindled dentate gyrus 2 h after the last kindling stimulation. A similar increase in basal PKC activity was observed in dentate gyrus 2 h after the first kindling stimulation. These results document a kindling-associated persistent PKC activation and suggest that the increased activity of PKC could play a role in the induction of the kindling effect.

  14. Effect of piperine on the epididymis of adult male rats

    Institute of Scientific and Technical Information of China (English)

    S. C. D'cruz; P. P. Mathur

    2005-01-01

    Aim: To study the effect of piperine on the epididymal antioxidant system of adult male rats. Methods: Adult male rats were orally administered piperine at doses of 1 mg/kg, 10 mg/kg and 100 mg/kg body weight each day for 30consecutive days. Twenty-four hours after the last treatment, the rats were weighed and killed with ether and the epididymis was dissected from the bodies. Sperm collected from the cauda region of the epididymis was used for the assessment of its count, motility and viability. Caput, corpus and cauda regions of the epididymis were separated and homogenized separately to obtain 10 % homogenates. The supernatants were used for the assays of sialic acid,superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, lipid peroxidation and hydrogen peroxide generation. Results: Body weight of the piperine-treated rats remained unchanged. The weights of the caput,corpus and cauda regions of the epididymis significantly decreased at dose of 100 mg/kg. Epididymal sperm count and motility decreased at 10 mg/kg and 100 mg/kg, and sperm viability decreased significantly at 100 mg/kg. Sialic acid levels in the epididymis decreased significantly at 100 mg/kg while significant decrease in the cauda region alone was observed at 10 mg/kg. A significant decline in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, along with an increase in hydrogen peroxide generation and lipid peroxidation were observed at 10 mg/kg and 100 mg/kg. Conclusion: Piperine caused a decrease in the activity of antioxidant enzymes and sialic acid levels in the epididymis and thereby increased reactive oxygen species levels that could damage the epididymal environment and sperm function.

  15. Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

    DEFF Research Database (Denmark)

    McCarthy, K J; Couchman, J R

    1990-01-01

    Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... sulfate proteoglycans previously described....

  16. Protective role of melatonin in domoic acid-induced neuronal damage in the hippocampus of adult rats.

    Science.gov (United States)

    Ananth, C; Gopalakrishnakone, P; Kaur, C

    2003-01-01

    Domoic acid (DA), a kainite-receptor agonist and potent inducer of neurotoxicity, has been administered intravenously in adult rats in the present study (0.75 mg/kg body weight) to demonstrate neuronal degeneration followed by glial activation and their involvement with inducible nitric oxide synthase (iNOS) in the hippocampus. An equal volume of normal saline was administered in control rats. The pineal hormone melatonin, which protects the neurons efficiently against excitotoxicity mediated by sensitive glutamate receptor, was administered intraperitoneally (10 mg/kg body weight), 20 min before, immediately after, and 1 h and 2 h after the DA administration, to demonstrate its role in therapeutic strategy. Histopathological analysis (Nissl staining) demonstrated extensive neuronal damage in the pyramidal neurons of CA1, CA3 subfields and hilus of the dentate gyrus (DG) in the hippocampus at 5 days after DA administration. Sparsely distributed glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were observed in the hippocampus at 4-24 h after DA administration and in the control rats. Astrogliosis was evidenced by increased GFAP immunoreactivity in the areas of severe neuronal degeneration at 5 days after DA administration. Along with this, microglial cells exhibited an intense immunoreaction with OX-42, indicating upregulation of complement type 3 receptors (CR3). Ultrastructural study revealed swollen or shrunken degenerating neurons in the CA1, CA3 subfields and hilus of the DG and hypertrophied astrocytes showing accumulation of intermediate filament bundles in the cytoplasm were observed after administration of DA. Although no significant change could be observed in the mRNA level of iNOS expression between the DA-treated rats and controls at 4-24 h and at 5-day time intervals, double immunofluorescense revealed co-expression of induced iNOS with GFAP immunoreactive astrocytes, but not in the microglial cells, and iNOS expression in the neurons

  17. High Threshold, Proximal Initiation, and Slow Conduction Velocity of Action Potentials in Dentate Granule Neuron Mossy Fibers

    OpenAIRE

    Kress, Geraldine J.; Dowling, Margaret J.; Meeks, Julian P.; Mennerick, Steven

    2008-01-01

    Dentate granule neurons give rise to some of the smallest unmyelinated fibers in the mammalian CNS, the hippocampal mossy fibers. These neurons are also key regulators of physiological and pathophysiological information flow through the hippocampus. We took a comparative approach to studying mossy fiber action potential initiation and propagation in hippocampal slices from juvenile rats. Dentate granule neurons exhibited axonal action potential initiation significantly more proximal than CA3 ...

  18. Density of mu-opioid receptors in the hippocampus of adult male and female rats is altered by prenatal morphine exposure and gonadal hormone treatment.

    Science.gov (United States)

    Slamberová, Romana; Rimanóczy, Agnes; Bar, Noffar; Schindler, Cheryl J; Vathy, Ilona

    2003-01-01

    The present in vitro autoradiography study demonstrates that prenatal exposure to morphine alters the density of mu-opioid receptors in the hippocampus of adult female but not adult male rats. Prenatal morphine exposure increased the mu-opioid receptor density in the CA1 of ovariectomized (OVX) females and in the CA3 of OVX, estradiol benzoate-plus progesterone (EB+P)-treated females, but decreased it in CA3 of OVX females. There were also hormonal effects on mu-opioid receptor density in adult female rats. In the CA1, only morphine-exposed but not saline-exposed, hormone-treated females (EB, P, or EB+P) had a decrease in mu-opioid receptor density relative to OVX females. Both saline-exposed and morphine-exposed, OVX females after gonadal hormone replacement had a lower density of mu-opioid receptors in the CA3 and in the dentate gyrus (DG) than OVX females. In male rats, there was a decrease in mu-opioid receptor density in the CA1 and CA3 of gonadectomized (GNX), testosterone 17beta-proprionate (TP)-treated males relative to GNX males regardless of prenatal morphine exposure. In the DG, the mu-opioid receptor density was reduced only in morphine-exposed but not in saline-exposed, TP-treated males compared with GNX males. Thus, our data demonstrate that mu-opioid receptor density in the hippocampus is affected by prenatal morphine exposure and by male and female gonadal hormones.

  19. Neurogenesis induced by seizures in the dentate gyrus is not related to mossy fiber sprouting but is age dependent in developing rats A neurogênese induzida por crises no giro denteado não está relacionada ao brotamento de fibras musgosas, mas é dependente da idade, em ratos durante o desenvolvimento

    Directory of Open Access Journals (Sweden)

    Yaima del Carmen Garrido Sanabria

    2008-12-01

    Full Text Available Neurogenesis in the dentate gyrus (DG has attracted attention since abnormal supragranular mossy fiber sprouting occurs in the same region, in temporal lobe epilepsy. Thus, we submitted developing rats to pilocarpine-induced status epilepticus (SE to study the relationship between neurogenesis and mossy fiber sprouting. Groups were submitted to SE at: I-P9, II-P7, P8 and P9, III-P17 e IV-P21. Neurogenesis was quantified using BrdU protocol and confirmed through double staining, using neuronal pentraxin. Other animals were monitored by video system until P120 and their brain was studied (Timm and Nissl staining. The neurogenesis at P17 (p=0.007 and P21 (p=0.006 were increased. However, only P21 group showed recurrent seizures and the mossy fiber sprouting in the same region, during adult life, while P17 did not. Thus, our results suggest that neurogenesis is not related to mossy fiber sprouting neither to recurrent spontaneous seizures in pilocarpine model.A neurogênese no giro dentado tem atraído atenção já que ela ocorre na mesma região do hipocampo que o brotamento das fibras musgosas, na epilepsia do lobo temporal. Assim, submetemos ratos em desenvolvimento ao status epilepticus induzido (SE por pilocarpine. Grupos foram submetidos em I-P9, II-P7, P8, P9; III-P17 e IV-P21. A neurogênese foi observada usando o protocolo do BrdU e confirmada por dupla marcação com pentraxina neuronal. Outros animais foram monitorados até P120 e seus cérebros analisados (Nissl e Timm. A neurogênese nos grupos P17 (p=0,007 e P21 (p=0,006 aumentaram. Entretanto, o P21 apresentou crises espontâneas e brotamento de fibras musgosas, na mesma região onde ocorreu a neurogênese, enquanto o grupo P17 apresentou somente aumento na neurogênese. Assim, nossos resultados sugerem que o fenômeno da neurogênese não está relacionado com o brotamento de fibras musgosas nem com o aparecimento de crises espontâneas e recorrentes no modelo da pilocarpina.

  20. Antisense to the glucocorticoid receptor in hippocampal dentate gyrus reduces immobility in forced swim test

    NARCIS (Netherlands)

    Korte, S.M.; de Kloet, E.R.; Buwalda, B; Bouman, S.D.; Bohus, B

    1996-01-01

    Immobility time of rats in the forced swim test was reduced after bilateral infusion of an 18-mer antisense phosphorothioate oligodeoxynucleotide targeted to the glucocorticoid receptor mRNA into the dentate gyrus of the hippocampus. Vehicle-, sense- and scrambled sequence-treated animals spent sign

  1. Dobutamine stress echocardiography in healthy adult male rats

    Directory of Open Access Journals (Sweden)

    Couet Jacques

    2005-10-01

    Full Text Available Abstract Background Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe. Results Dobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate. Conclusion DSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.

  2. Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

    Science.gov (United States)

    Aly, Hamdy A A; Mansour, Ahmed M; Hassan, Memy H; Abd-Ellah, Mohamed F

    2016-08-01

    The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016.

  3. Acute behavioral toxicity of carbaryl and propoxur in adult rats.

    Science.gov (United States)

    Ruppert, P H; Cook, L L; Dean, K F; Reiter, L W

    1983-04-01

    Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8, 16 or 28 mg/kg carbaryl in corn oil 20 min before testing. All doses of propoxur reduced 2 hr activity in a figure-eight maze, and crossovers and rears in an open field. For carbaryl, dosages of 8, 16 and 28 mg/kg decreased maze activity whereas 16 and 28 mg/kg reduced open field activity. In order to determine the time course of effects, rats received a single IP injection of either corn oil, 2 mg/kg propoxur or 16 mg/kg carbaryl, and were tested for 5 min in a figure-eight maze either 15, 30, 60, 120 or 240 min post-injection. Immediately after testing, animals were sacrificed and total cholinesterase was measured. Maximum effects of propoxur and carbaryl on blood and brain cholinesterase and motor activity were seen within 15 min. Maze activity had returned to control levels within 30 and 60 min whereas cholinesterase levels remained depressed for 120 and 240 min for propoxur and carbaryl, respectively. These results indicate that both carbamates decrease motor activity, but behavioral recovery occurs prior to that of cholinesterase following acute exposure.

  4. Effects of neonatal peripheral tissue injury on pain-related behaviors in adult rats

    Directory of Open Access Journals (Sweden)

    Meng-meng LI

    2013-09-01

    Full Text Available Objective To observe the effects of peripheraltissueinjury in the developmental stage of newborn rats on pain-related behaviors in adult rats. Methods SD rats 1,4,7,14,21 and 28days after birth were selected in thepresent study(4litters at each time point and 10 rats per litter.Each litter of rats was randomly divided intoinjury group(receiving subcutaneous injection of 20μl bee venomand control group(receiving subcutaneous injection of 20μl normal saline, with20 in each group, and then raised for 2 months to adulthood. The baseline pain threshold was observed by measuring spontaneous paw flinching reflex,paw withdrawal thermal latency(PWTLand paw withdrawal mechanical threshold(PWMT, then 50μl 0.4% bee venom was subcutaneously injected to each rat, and the changesinpa in reaction and pain threshold were determined. Results The baseline thermal pain threshold in adult rats receiving bee venom or normal saline at different time points after birth was similar,but baseline mechanical pain threshold in adult rats receiving bee venom at1,4,7and14 days after birth was decreased significantly compared with the adult rats receiving normal saline at corresponding time points(P0.05.Mechanical hyperalgesia was not induced in rats injected with bee venom but induced in adult ratsinjected with normal saline4-21days after birth.Injection of bee venom 21 and 28 days after birth could obviously enhance the bee venom-induced hyperalgesiain adult rats compared with control group(P<0.01. Conclusions Bee venom stimuli at different time points after birth could affect the baseline PWMT and mechanical pain hypersensitivityin adult rats but not the baseline PWTL and thermal pain hypersensitivity. The 21st day maybe a key time point of nervous system development in rats.

  5. Neonatal caffeine exposure and seizure susceptibility in adult rats.

    Science.gov (United States)

    Guillet, R; Dunham, L

    1995-08-01

    Early developmental exposure to caffeine in rats results in changes in brain excitability that persist to adulthood. The mechanism of these alterations is unknown. To identify potential neurotransmitter systems involved, we exposed neonatal rats to caffeine and determined seizure thresholds for chemoconvulsants active at different CNS receptors in the adult animal. Rats were unhandled (NH) or received by gavage (0.05 ml/10 g) either vehicle (water) or caffeine (15-20 mg/kg/day) for postnatal days 2-6. At age 70-90 days, each rat was infused intravenously (i.v.) with picrotoxin (PIC), bicuculline (BIC) [convulsants acting at the gamma-aminobutyric acid/benzodiazepine (GABA/BDZ) receptor], pentylenetetrazol [PTZ, possibly acting at both GABA/BDZ and N-methyl-D-aspartate (NMDA) receptors], caffeine (acting at adenosine receptors), strychnine (STR, acting at glycine receptors), or kainic acid (KA, acting at the NMDA receptor). Seizure thresholds were analyzed as a function of neonatal treatment and sex. Thresholds for caffeine, PTZ, PIC, and KA were increased as a function of neonatal caffeine exposure (p = 0.01, 0.02, 0.02, and 0.005, respectively). The thresholds for BIC and STR were not altered. There were also gender differences in seizure susceptibility. Thresholds for seizures produced by BIC, caffeine, PIC, and STR were higher in females (p = 0.005, 0.005, 0.001, and 0.0001, respectively), but were not different for seizures caused by PTZ. These results suggest that early developmental exposure to caffeine affects later seizure susceptibility. Moreover, some of these effects are gender specific.

  6. Increases in Doublecortin Immunoreactivity in the Dentate Gyrus following Extinction of Heroin-Seeking Behavior

    Directory of Open Access Journals (Sweden)

    Megan P. Hicks

    2012-01-01

    Full Text Available Adult-generated neurons in the dentate gyrus (DG of the hippocampus play a role in various forms of learning and memory. However, adult born neurons in the DG, while still at an immature stage, exhibit unique electrophysiological properties and are also functionally implicated in learning and memory processes. We investigated the effects of extinction of drug-seeking behavior on the formation of immature neurons in the DG as assessed by quantification of doublecortin (DCX immunoreactivity. Rats were allowed to self-administer heroin (0.03 mg/kg/infusion for 12 days and then subjected either to 10 days of extinction training or forced abstinence. We also examined extinction responding patterns following heroin self-administration in glial fibrillary acidic protein thymidine kinase (GFAP-tk transgenic mice, which have been previously demonstrated to show reduced formation of immature and mature neurons in the DG following treatment with ganciclovir (GCV. We found that extinction training increased DCX immunoreactivity in the dorsal DG as compared with animals undergoing forced abstinence, and that GCV-treated GFAP-tk mice displayed impaired extinction learning as compared to saline-treated mice. Our results suggest that extinction of drug-seeking behavior increases the formation of immature neurons in the DG and that these neurons may play a functional role in extinction learning.

  7. Increases in doublecortin immunoreactivity in the dentate gyrus following extinction of heroin-seeking behavior.

    Science.gov (United States)

    Hicks, Megan P; Wischerath, Kelly C; Lacrosse, Amber L; Olive, M Foster

    2012-01-01

    Adult-generated neurons in the dentate gyrus (DG) of the hippocampus play a role in various forms of learning and memory. However, adult born neurons in the DG, while still at an immature stage, exhibit unique electrophysiological properties and are also functionally implicated in learning and memory processes. We investigated the effects of extinction of drug-seeking behavior on the formation of immature neurons in the DG as assessed by quantification of doublecortin (DCX) immunoreactivity. Rats were allowed to self-administer heroin (0.03 mg/kg/infusion) for 12 days and then subjected either to 10 days of extinction training or forced abstinence. We also examined extinction responding patterns following heroin self-administration in glial fibrillary acidic protein thymidine kinase (GFAP-tk) transgenic mice, which have been previously demonstrated to show reduced formation of immature and mature neurons in the DG following treatment with ganciclovir (GCV). We found that extinction training increased DCX immunoreactivity in the dorsal DG as compared with animals undergoing forced abstinence, and that GCV-treated GFAP-tk mice displayed impaired extinction learning as compared to saline-treated mice. Our results suggest that extinction of drug-seeking behavior increases the formation of immature neurons in the DG and that these neurons may play a functional role in extinction learning.

  8. Contractile force measured in unskinned isolated adult rat heart fibres.

    Science.gov (United States)

    Brady, A J; Tan, S T; Ricchiuti, N V

    1979-12-13

    A number of investigators have succeeded in preparing isolated cardiac cells by enzymatic digestion which tolerate external [Ca2+] in the millimolar range. However, a persistent problem with these preparations is that, unlike in situ adult ventricular fibres, the isolated fibres usually beat spontaneously. This spontaneity suggests persistent ionic leakage not present in situ. A preferable preparation for mechanical and electrical studies would be one which is quiescent but excitable in response to electrical stimulation and which does not undergo contracture with repeated stimulation. We report here a modified method of cardiac fibre isolation and perfusion which leaves the fibre membrane electrically excitable and moderately resistant to mechanical stress so that the attachment of suction micropipettes to the fibre is possible for force measurement and length control. Force generation in single isolated adult rat heart fibres is consistent with in situ contractile force. The negative staircase effect (treppe) characteristic of adult not heart tissue is present with increased frequency of stimulation. Isometric developed tension increases with fibre length as in in situ ventricular tissue.

  9. Effects of combined nicotine and fluoxetine treatment on adult hippocampal neurogenesis and conditioned place preference.

    Science.gov (United States)

    Faillace, M P; Zwiller, J; Bernabeu, R O

    2015-08-06

    Adult neurogenesis occurs in mammals within the dentate gyrus, a hippocampal subarea. It is known to be induced by antidepressant treatment and reduced in response to nicotine administration. We checked here whether the antidepressant fluoxetine would inverse the decrease in hippocampal neurogenesis caused by nicotine. It is shown that repeated, but not a single injection of rats with fluoxetine was able to abolish the decrease in adult dentate cell proliferation produced by nicotine treatment. We measured the expression of several biochemical parameters known to be associated with neurogenesis in the dentate gyrus. Both drugs increased the expression of p75 neurotrophin receptor, which promotes proliferation and early maturation of dentate gyrus cells. Using the conditioned place preference (CPP) paradigm, we also gave both drugs in a context in which their rewarding properties could be measured. Fluoxetine produced a significant but less robust CPP than nicotine. A single injection of fluoxetine was found to reduce nicotine-induced CPP. Moreover, the rewarding properties of nicotine were completely abolished in response to repeated fluoxetine injections. Expression of nicotine-induced CPP was accompanied by an increase of phospho-CREB (cyclic AMP-responsive element-binding protein) and HDAC2 (histone deacetylase 2) expression in the nucleus accumbens. The data suggest that fluoxetine reward, as opposed to nicotine reward, depends on dentate gyrus neurogenesis. Since fluoxetine was able to disrupt the association between nicotine and the environment, this antidepressant may be tested as a treatment for nicotine addiction using cue exposure therapy.

  10. Status Epilepticus Induced Spontaneous Dentate Gyrus Spikes: In Vivo Current Source Density Analysis.

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    Sean P Flynn

    Full Text Available The dentate gyrus is considered to function as an inhibitory gate limiting excitatory input to the hippocampus. Following status epilepticus (SE, this gating function is reduced and granule cells become hyper-excitable. Dentate spikes (DS are large amplitude potentials observed in the dentate gyrus (DG of normal animals. DS are associated with membrane depolarization of granule cells, increased activity of hilar interneurons and suppression of CA3 and CA1 pyramidal cell firing. Therefore, DS could act as an anti-excitatory mechanism. Because of the altered gating function of the dentate gyrus following SE, we sought to investigate how DS are affected following pilocarpine-induced SE. Two weeks following lithium-pilocarpine SE induction, hippocampal EEG was recorded in male Sprague-Dawley rats with 16-channel silicon probes under urethane anesthesia. Probes were placed dorso-ventrally to encompass either CA1-CA3 or CA1-DG layers. Large amplitude spikes were detected from EEG recordings and subject to current source density analysis. Probe placement was verified histologically to evaluate the anatomical localization of current sinks and the origin of DS. In 9 of 11 pilocarpine-treated animals and two controls, DS were confirmed with large current sinks in the molecular layer of the dentate gyrus. DS frequency was significantly increased in pilocarpine-treated animals compared to controls. Additionally, in pilocarpine-treated animals, DS displayed current sinks in the outer, middle and/or inner molecular layers. However, there was no difference in the frequency of events when comparing between layers. This suggests that following SE, DS can be generated by input from medial and lateral entorhinal cortex, or within the dentate gyrus. DS were associated with an increase in multiunit activity in the granule cell layer, but no change in CA1. These results suggest that following SE there is an increase in DS activity, potentially arising from

  11. Postnatal morphine administration alters hippocampal development in rats.

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    Traudt, Christopher M; Tkac, Ivan; Ennis, Kathleen M; Sutton, Leah M; Mammel, Daniel M; Rao, Raghavendra

    2012-01-01

    Morphine is frequently used as an analgesic and sedative in preterm infants. Adult rats exposed to morphine have an altered hippocampal neurochemical profile and decreased neurogenesis in the dentate gyrus of the hippocampus. To evaluate whether neonatal rats are similarly affected, rat pups were injected twice daily with 2 mg/kg morphine or normal saline from postnatal days 3 to 7. On postnatal day 8, the hippocampal neurochemical profile was determined using in vivo (1)H NMR spectroscopy. The mRNA and protein concentrations of specific analytes were measured in hippocampus, and cell division in dentate gyrus was assessed using bromodeoxyuridine. The concentrations of γ-aminobutyric acid (GABA), taurine, and myo-insotol were decreased, whereas concentrations of glutathione, phosphoethanolamine, and choline-containing compounds were increased in morphine-exposed rats relative to control rats. Morphine decreased glutamic acid decarboxylase enzyme levels and myelin basic protein mRNA expression in the hippocampus. Bromodeoxyuridine labeling in the dentate gyrus was decreased by 60-70% in morphine-exposed rats. These results suggest that recurrent morphine administration during brain development alters hippocampal structure.

  12. Behavioral effects of subchronic inhalation of toluene in adult rats.

    Science.gov (United States)

    Beasley, Tracey E; Evansky, Paul A; Gilbert, Mary E; Bushnell, Philip J

    2010-01-01

    Whereas the acute neurobehavioral effects of toluene are robust and well characterized, evidence for persistent effects of repeated exposure to this industrial solvent is less compelling. The present experiment sought to determine whether subchronic inhalation of toluene caused persistent behavioral changes in rats. Adult male Long-Evans rats inhaled toluene vapor (0, 10, 100, or 1000 ppm) for 6h/day, 5 days/week for 13 weeks and were evaluated on a series of behavioral tests beginning 3 days after the end of exposure. Toluene delayed appetitively-motivated acquisition of a lever-press response, but did not affect motor activity, anxiety-related behavior in the elevated plus maze, trace fear conditioning, acquisition of an appetitively-motivated visual discrimination, or performance of a visual signal detection task. Challenges with acute inhalation of toluene vapor (1200-2400 ppm for 1 h) and injections of quinpirole (0.01-0.03 mg/kg) and raclopride (0.03-0.10 mg/kg) revealed no toluene-induced latent impairments in visual signal detection. These results are consistent with a pattern of subtle and inconsistent long-term effects of daily exposure to toluene vapor, in contrast to robust and reliable effects of acute inhalation of the solvent.

  13. Combined neonatal stress and young-adult glucocorticoid stimulation in rats reduce BDNF expression in hippocampus: effects on learning and memory.

    Science.gov (United States)

    Choy, Kwok Ho Christopher; de Visser, Yvonne; Nichols, Nancy R; van den Buuse, Maarten

    2008-01-01

    Epidemiological studies suggest that multiple developmental disruptions are involved in the etiology of psychiatric illnesses including schizophrenia. In addition, altered expression of brain-derived neurotrophic factor (BDNF) has been implicated in these illnesses. In the present study, we examined the combined long-term effect of an early stress, in the form of maternal deprivation, and a later stress, simulated by chronic young-adult treatment with the stress hormone, corticosterone, on BDNF expression in the hippocampus of rats. To assess whether there were behavioral effects, which may correlate with the BDNF changes, learning and memory was tested in the Y-maze test for short term spatial memory, the Morris water maze for long-term spatial memory, and the T-maze test for working memory. Four groups of rats received either no stress, maternal deprivation, corticosterone treatment, or both. Dorsal hippocampus sections obtained from parallel groups were used for BDNF mRNA in situ hybridization. Rats which had undergone both maternal deprivation and corticosterone treatment displayed a unique and significant 25-35% reduction of BDNF expression in the dentate gyrus (DG), and similar trends in the CA1 and CA3 regions of the hippocampus. These "two-hit" animals exhibited a learning delay in the Morris water maze test, a marked deficit in the Y-maze, but little change in the T-maze test. However, some aspects of cognition were also altered in rats with either maternal deprivation or corticosterone treatment. This study demonstrates a persistent effect of two developmental disruptions on BDNF expression in the hippocampus, with parallel, but not completely correlative changes in learning and memory.

  14. Mixed Electrical-Chemical Synapses in Adult Rat Hippocampus are Primarily Glutamatergic and Coupled by Connexin-36.

    Science.gov (United States)

    Hamzei-Sichani, Farid; Davidson, Kimberly G V; Yasumura, Thomas; Janssen, William G M; Wearne, Susan L; Hof, Patrick R; Traub, Roger D; Gutiérrez, Rafael; Ottersen, Ole P; Rash, John E

    2012-01-01

    Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neuronal communication in mammalian brain, whereas axodendritic and axosomatic gap junctions have rarely been described. We present ultrastructural, immunocytochemical, and dye-coupling evidence for "mixed" (electrical/chemical) synapses on both principal cells and interneurons in adult rat hippocampus. Thin-section electron microscopic images of small gap junction-like appositions were found at mossy fiber (MF) terminals on thorny excrescences of CA3 pyramidal neurons (CA3pyr), apparently forming glutamatergic mixed synapses. Lucifer Yellow injected into weakly fixed CA3pyr was detected in MF axons that contacted four injected CA3pyr, supporting gap junction-mediated coupling between those two types of principal cells. Freeze-fracture replica immunogold labeling revealed diverse sizes and morphologies of connexin-36-containing gap junctions throughout hippocampus. Of 20 immunogold-labeled gap junctions, seven were large (328-1140 connexons), three of which were consistent with electrical synapses between interneurons; but nine were at axon terminal synapses, three of which were immediately adjacent to distinctive glutamate receptor-containing postsynaptic densities, forming mixed glutamatergic synapses. Four others were adjacent to small clusters of immunogold-labeled 10-nm E-face intramembrane particles, apparently representing extrasynaptic glutamate receptor particles. Gap junctions also were on spines in stratum lucidum, stratum oriens, dentate gyrus, and hilus, on both interneurons and unidentified neurons. In addition, one putative GABAergic mixed synapse was found in thin-section images of a CA3pyr, but none were found by immunogold labeling, suggesting the rarity of GABAergic mixed synapses. Cx36-containing gap junctions throughout hippocampus suggest the possibility of reciprocal modulation of electrical and chemical signals in diverse hippocampal neurons.

  15. Mixed electrical-chemical synapses in adult rat hippocampus are primarily glutamatergic and coupled by connexin-36

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    Farid eHamzei-Sichani

    2012-05-01

    Full Text Available Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neuronal communication in the mammalian brain, whereas axodendritic and axosomatic gap junctions have rarely been described. We present ultrastructural, immunocytochemical, and dye-coupling evidence for mixed (electrical/chemical synapses in adult rat hippocampus on both principal cells and interneurons. Thin-section electron microscopic images of small gap junction-like appositions were found at mossy fiber (MF terminals on thorny excrescences of CA3 pyramidal neurons (CA3pyr, apparently forming glutamatergic mixed synapses. Lucifer Yellow injected into four weakly-fixed CA3pyr was detected in MF axons that contacted the injected CA3pyr, supporting gap junction-mediated coupling between those two types of principal cells. Freeze-fracture replica immunogold-labeling revealed diverse sizes and morphologies of connexin36-containing gap junctions throughout hippocampus. Of 20 immunogold-labeled gap junctions, seven were large (328-1140 connexons, three of which were consistent with electrical synapses between interneurons; but nine were at axon terminal synapses, three of which were immediately adjacent to distinctive glutamate receptor-containing postsynaptic densities, forming mixed glutamatergic synapses. Four others were adjacent to small clusters of immunogold-labeled 10-nm E-face intramembrane particles, apparently representing extrasynaptic glutamate receptor particles. Gap junctions also were on spines in stratum lucidum, stratum oriens, dentate gyrus, and hilus, on both interneurons and unidentified neurons. In addition, one putative GABAergic mixed synapse was found in thin section images of a CA3pyr, but none found by immunogold-labeling were at GABAergic mixed synapses, suggesting their rarity. Cx36-containing gap junctions throughout hippocampus suggest the possibility of reciprocal modulation of electrical and chemical signals in diverse hippocampal

  16. Neonatal injections of methoxychlor decrease adult rat female reproductive behavior.

    Science.gov (United States)

    Bertolasio, Jennifer; Fyfe, Susanne; Snyder, Ben W; Davis, Aline M

    2011-12-01

    Methoxychlor (MXC), a commonly used pesticide, has been labeled as an endocrine disruptor. To evaluate the impact of neonatal exposure to MXC on female reproduction, female Sprague-Dawley rats were given subcutaneous injections on postnatal days 1, 3, and 5. The injections contained 1.0mg MXC, 2.0mg MXC, 10 μg 17β-estradiol benzoate (positive control), or sesame oil (vehicle). The injections of MXC had no effect on anogenital distance or day of vaginal opening. Treatment with either 2.0mg MXC or estradiol significantly increased the total number of days with vaginal keratinization. Treatment with MXC had no effect on ability to exhibit a mating response as an adult female, although the high dose MXC (2.0) and the positive control (estradiol) animals demonstrated a decrease in degree of receptivity, a decrease in proceptive behavior and an increase in rejection behavior. These data suggest that higher doses of MXC given directly to pups during the neonatal period can act as an estrogen and alter aspects of the nervous system, impacting adult reproductive characteristics.

  17. The proteome of neural stem cells from adult rat hippocampus

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    Fütterer Carsten D

    2003-06-01

    Full Text Available Abstract Background Hippocampal neural stem cells (HNSC play an important role in cerebral plasticity in the adult brain and may contribute to tissue repair in neurological disease. To describe their biological potential with regard to plasticity, proliferation, or differentiation, it is important to know the cellular composition of their proteins, subsumed by the term proteome. Results Here, we present for the first time a proteomic database for HNSC isolated from the brains of adult rats and cultured for 10 weeks. Cytosolic proteins were extracted and subjected to two-dimensional gel electrophoresis followed by protein identification through mass spectrometry, database search, and gel matching. We could map about 1141 ± 209 (N = 5 protein spots for each gel, of which 266 could be identified. We could group the identified proteins into several functional categories including metabolism, protein folding, energy metabolism and cellular respiration, as well as cytoskeleton, Ca2+ signaling pathways, cell cycle regulation, proteasome and protein degradation. We also found proteins belonging to detoxification, neurotransmitter metabolism, intracellular signaling pathways, and regulation of DNA transcription and RNA processing. Conclusions The HNSC proteome database is a useful inventory which will allow to specify changes in the cellular protein expression pattern due to specific activated or suppressed pathways during differentiation or proliferation of neural stem cells. Several proteins could be identified in the HNSC proteome which are related to differentiation and plasticity, indicating activated functional pathways. Moreover, we found a protein for which no expression has been described in brain cells before.

  18. Primary culture of adult rat liver cells. I. Preparation of isolated cells from trypsin-perfused liver of adult rat

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    Miyazaki,Masahiro

    1977-12-01

    Full Text Available Isolated hepatic cells from adult rats were prepared by perfusing the livers with trypsin. The highest yield of viable cells was obtained by perfusing the liver with 0.1% trypsin, pH 7.0, at 37 degrees C for 30 min. Following this treatment about 70% of cells excluded trypan blue. The isolated cells contained many binucleate cells. Between 60 and 70% of DNA present originally in the liver was recovered from the isolated hepatic cells, which had higher glucose 6-phosphatase activity than the liver. Thus the resulting cell population seems to be rich in hepatocytes. The isolated hepatic cells, however, lost some of their cellular proteins such as alanine and tyrosine amino-transferases. It was suggested that the membranes of isolated hepatic cells might be damaged by both enzymatic digestion and mechanical destruction.

  19. Microglia engulf viable newborn cells in the epileptic dentate gyrus.

    Science.gov (United States)

    Luo, Cong; Koyama, Ryuta; Ikegaya, Yuji

    2016-09-01

    Microglia, which are the brain's resident immune cells, engulf dead neural progenitor cells during adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG). The number of newborn cells in the SGZ increases significantly after status epilepticus (SE), but whether and how microglia regulate the number of newborn cells after SE remain unclear. Here, we show that microglia rapidly eliminate newborn cells after SE by primary phagocytosis, a process by which viable cells are engulfed, thereby regulating the number of newborn cells that are incorporated into the DG. The number of newborn cells in the DG was increased at 5 days after SE in the adult mouse brain but rapidly decreased to the control levels within a week. During this period, microglia in the DG were highly active and engulfed newborn cells. We found that the majority of engulfed newborn cells were caspase-negative viable cells. Finally, inactivation of microglia with minocycline maintained the increase in the number of newborn cells after SE. Furthermore, minocycline treatment after SE induced the emergence of hilar ectopic granule cells. Thus, our findings suggest that microglia may contribute to homeostasis of the dentate neurogenic niche by eliminating excess newborn cells after SE via primary phagocytosis. GLIA 2016;64:1508-1517.

  20. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    Science.gov (United States)

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  1. Transformation of adult rat cardiac myocytes in primary culture.

    Science.gov (United States)

    Banyasz, Tamas; Lozinskiy, Ilya; Payne, Charles E; Edelmann, Stephanie; Norton, Byron; Chen, Biyi; Chen-Izu, Ye; Izu, Leighton T; Balke, C William

    2008-03-01

    We characterized the morphological, electrical and mechanical alterations of cardiomyocytes in long-term cell culture. Morphometric parameters, sarcomere length, T-tubule density, cell capacitance, L-type calcium current (I(Ca,L)), inward rectifier potassium current (I(K1)), cytosolic calcium transients, action potential and contractile parameters of adult rat ventricular myocytes were determined on each day of 5 days in culture. We also analysed the health of the myocytes using an apoptotic/necrotic viability assay. The data show that myocytes undergo profound morphological and functional changes during culture. We observed a progressive reduction in the cell area (from 2502 +/- 70 microm(2) on day 0 to 1432 +/- 50 microm(2) on day 5), T-tubule density, systolic shortening (from 0.11 +/- 0.02 to 0.05 +/- 0.01 microm) and amplitude of calcium transients (from 1.54 +/- 0.19 to 0.67 +/- 0.19) over 5 days of culture. The negative force-frequency relationship, characteristic of rat myocardium, was maintained during the first 2 days but diminished thereafter. Cell capacitance (from 156 +/- 8 to 105 +/- 11 pF) and membrane currents were also reduced (I(Ca,L), from 3.98 +/- 0.39 to 2.12 +/- 0.37 pA pF; and I(K1), from 34.34p +/- 2.31 to 18.00 +/- 5.97 pA pF(-1)). We observed progressive depolarization of the resting membrane potential during culture (from 77.3 +/- 2.5 to 34.2 +/- 5.9 mV) and, consequently, action potential morphology was profoundly altered as well. The results of the viability assays indicate that these alterations could not be attributed to either apoptosis or necrosis but are rather an adaptation to the culture conditions over time.

  2. Apoptosis and autophagy control cell proliferation in the dentate gyrus following hippocampal lesion

    Institute of Scientific and Technical Information of China (English)

    Ju Zhou; Wei Peng; Qi Zhu; Shan Gong; Lidong Shan; Tadashi Hisamitsu; Shiyu Guo; Xinghong Jiang

    2010-01-01

    Brain injuries often result in the promotion of cell proliferation in the hippocampal dentate gyrus(DG),but the number of newborn cells declines with time.However,the cause of this decline remains poorly understood.Elucidation of the fate of these newborn cells will further the understanding of the pathological process and treatment of brain injury.In the present study,the number of newborn cells was quantitatively analyzed using an unbiased stereological method following hippocampal lesion by kainic acid,in combination with detection of apoptosis and autophagy.Results revealed that hippocampal lesion resulted in a significantly increased number of 5-bromo-2-deoxyuridine(BrdU)-positive cells in the DG,which subsequently decreased with time.BrdU/cleaved caspase-3 double-labeled cells were detected in the granular cell layer and hilus of DG.However,expressions of LC3-11,Beclin 1,and p53 were upregulated,and pro-caspase-3 and Bcl-2 were downregulated.Results indicated that hippocampal lesion in adult rats resulted in significant cell proliferation in the DG,which subsequently reduced with time.In addition,results suggested that apoptosis and autophagic processes could regulate cell proliferation in the DG following hippocampal lesion.

  3. Influences of olfactory ensheathing cells transplantation on axonal regeneration in spinal cord of adult rats

    Institute of Scientific and Technical Information of China (English)

    沈慧勇; 唐勇; 吴燕峰; 陈燕涛; 程志安

    2002-01-01

    To observe whether olfactory ensheathing cells could be used to promote axonal regeneration in a spontaneously nonregenerating system. Methods: After laminectomy at the lower thoracic level, the spinal cords of adult rats were exposed and completely transected at T10. A suspension of ensheathing cells was injected into the lesion site in 12 adult rats, and control D/F-12 (1∶1 mixture of DMEM and Hams F-12) was injected in 12 adult rats. Six weeks and ten weeks after cell transplantation, the rats were evaluated by climbing test and motor evoked potentials (MEPs) monitoring. The samples were procured and studied with histologicl and immunohistochemical methods. Results: At the 6th week after cell transplantation, all the rats in both the transplanted and control groups were paraplegic and the MEPs could not be recorded. At the 10th week after cell transplantation, of 7 rats in the control group, 2 rats had muscles contraction of the lower extremities, 2 rats had hips and/or knees active movement; and 5 rats MEPs could be recorded in the hind limbs in the transplanted group (n=7). None of the rats in the control group had functional improvement and no MEPs recorded (n=7). Numerous regenerating axons were observed through the transplantation and continued to regenerate into the denervated host tract. Cell labelling using anti-Myelin Basic Protein (MBP) and anti-Nerve Growth Factor Receptor (anti-NGFR) indicated that the regenerated axons were derived from the appropriate neuronal source and that donor cells migrated into the denervated host tract. But axonal degeneration existed and regenerating axons were not observed within the spinal cords of the adult rats with only D/F-12 injection. Conclusions: The axonal regeneration in the transected adult rat spinal cord is possible after ensheathing cells transplantation.

  4. Tooth movement characteristics in relation to root resorption in young and adult rats

    NARCIS (Netherlands)

    Ren, Yijin; Maltha, Jaap C.; Kuijpers-Jagtman, Anne Marie

    2007-01-01

    The aim of this study was to investigate tooth movement characteristics in relation to root resorption in young and adult rats. Two groups of 30 rats each (aged 6 wk and 9-12 months, respectively) were used. Standardized orthodontic appliances were placed to move the maxillary molars mesially. Anima

  5. Glycidol induces axonopathy by adult-stage exposure and aberration of hippocampal neurogenesis affecting late-stage differentiation by developmental exposure in rats.

    Science.gov (United States)

    Akane, Hirotoshi; Shiraki, Ayako; Imatanaka, Nobuya; Akahori, Yumi; Itahashi, Megu; Ohishi, Takumi; Mitsumori, Kunitoshi; Shibutani, Makoto

    2013-07-01

    To investigate the neurotoxicity profile of glycidol and its effect on developmental hippocampal neurogenesis, pregnant Sprague Dawley rats were given drinking water containing 0, 100, 300, or 1000 ppm glycidol from gestational day 6 until weaning on day 21 after delivery. At 1000 ppm, dams showed progressively worsening gait abnormalities, and histopathological examination showed generation of neurofilament-L(+) spheroids in the cerebellar granule layer and dorsal funiculus of the medulla oblongata, central chromatolysis in the trigeminal nerve ganglion cells, and axonal degeneration in the sciatic nerves. Decreased dihydropyrimidinase-like 3(+) immature granule cells in the subgranular zone (SGZ) and increased immature reelin(+) or calbindin-2(+) γ-aminobutyric acid-ergic interneurons and neuron-specific nuclear protein (NeuN)(+) mature neurons were found in the dentate hilus of the offspring of the 1000 ppm group on weaning. Hilar changes remained until postnatal day 77, with the increases in reelin(+) and NeuN(+) cells being present at ≥ 300 ppm, although the SGZ change disappeared. Thus, glycidol caused axon injury in the central and peripheral nervous systems of adult rats, suggesting that glycidol targets the newly generating nerve terminals of immature granule cells, resulting in the suppression of late-stage hippocampal neurogenesis. The sustained hilar changes may be a sign of continued aberrations in neurogenesis and migration. The no-observed-adverse-effect level was determined to be 300 ppm (48.8mg/kg body weight/day) for dams and 100 ppm (18.5mg/kg body weight/day) for offspring. The sustained developmental exposure effect on offspring neurogenesis was more sensitive than the adult axonal injury.

  6. DOSE-DEPENDENT REDUCTIONS IN SPATIAL LEARING AND SYNAPTIC FUNCTION IN THE DENTATE GYRUS OF ADULT RATS FOLLOWING DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY.

    Science.gov (United States)

    The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

  7. Transmitter systems in the primate dentate gyrus.

    Science.gov (United States)

    Amaral, D G; Campbell, M J

    1986-01-01

    While the dentate gyrus is clearly the simplest of the cortical fields that constitute the hippocampal formation, it nonetheless occupies a pivotal position in the flow of information through this region. Though it has been the subject of anatomical study for over a century and its major connections have been known for almost as long, the use of newly developed histochemical and immunohistochemical techniques have demonstrated many new facets of its intrinsic connectivity and afferent innervation. These techniques have established that it is innervated by cholinergic, noradrenergic, serotonergic and dopaminergic fibers. More recent studies have shown that fibers and cell bodies of the dentate gyrus are immunoreactive for variety of neuroactive substances including the excitatory amino acids glutamate and aspartate, the inhibitory transmitter GABA, as well as peptides of many types including the opioid peptides, enkephalin and dynorphin, several forms of somatostatin, neuropeptide Y, cholycystokinin, vasoactive intestinal peptide and substance P. In this review, we will briefly summarize the distribution of each of these putative transmitter systems within the dentate gyrus. The perspective emerges that the plethora of newly identified and chemically specific fiber systems enriches the classical understanding of the organization of this relatively simple cortical structure. Since there is thus far no evidence for the exclusion from the dentate gyrus of any class of transmitter bearing fiber or neuron found in the neocortex, it can be viewed as a relatively simple model system for studying the interactions of specific transmitter systems in a laminated, cortical structure.

  8. Adolescent and adult male spontaneous hyperactive rats (SHR) respond differently to acute and chronic methylphenidate (Ritalin).

    Science.gov (United States)

    Barron, Elyssa; Yang, Pamela B; Swann, Alan C; Dafny, Nachum

    2009-01-01

    Eight groups of male adolescent and adult spontaneous hyperactive rats (SHR) were used in a dose response (saline, 0.6, 2.5, and 10 mg/kg) experiment of methylphenidate (MPD). Four different locomotor indices were recorded for 2 hours postinjection using a computerized monitoring system. Acutely, the 0.6 mg/kg dose of MPD did not elicit an increase in locomotor activity in either the adolescent or in the adult male SHR. The 2.5 and the 10.0 mg/kg doses increased activity in the adolescent and the adult rats. Chronically, MPD treatment when comparing adolescent and adult gave the following results: the 0.6 mg/kg dose of MPD failed to cause sensitization in the adolescent group but caused sensitization in the adult group, while the 2.5 and 10 mg/kg both caused sensitization in the adolescent and adult groups.

  9. Prenatal exposure to ethanol causes partial diabetes insipidus in adult rats.

    Science.gov (United States)

    Knee, Daniel S; Sato, Aileen K; Uyehara, Catherine F T; Claybaugh, John R

    2004-08-01

    Chronic consumption of ethanol in adult rats and humans leads to reduced AVP-producing neurons, and prenatal ethanol (PE) exposure has been reported to cause changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus of young rats. The present studies further characterize the effects of PE exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet with 35% of the calories from ethanol or a control liquid diet for days 7-22 of pregnancy. Water consumption and urine excretion rate were measured in the offspring at 60-68 days of age. Subsequently, the offspring were infused with 5% NaCl at 0.05 ml.kg(-1).min(-1) with plasma samples taken before and at three 40-min intervals during infusion for measurement of AVP and osmolality. Urine output and water intake were approximately 20% greater in PE-exposed rats than in rats with no PE exposure, and female rats had a greater water intake than males. The relationship between plasma osmolality and AVP in PE-exposed rats was parallel to, but shifted to the right of, the control rats, indicating an increase in osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and hypothalamic AVP mRNA content was reduced by 35% in PE-exposed rats. Our data suggest that PE exposure can cause a permanent condition of a mild partial central diabetes insipidus.

  10. Effects of prenatal chronic mild stress exposure on hippocampal cell proliferation, expression of GSK-3α, β and NR2B in adult offspring during fear extinction in rats.

    Science.gov (United States)

    Li, Min; Li, Xiaobai; Zhang, Xinxin; Ren, Jintao; Jiang, Han; Wang, Yan; Ma, Yuchao; Cheng, Wenwen

    2014-06-01

    Stress during pregnancy has been implicated as a risk factor for the development of many mental disorders; however, the influence of prenatal stress on the fear or anxiety-related behaviors, especially the fear extinction in adult offspring has been little investigated. In order to investigate how prenatal stress affects fear extinction, which is regarded as a form of new learning that counteracts the expression of Pavlovian's conditioned fear, a rat model of prenatal chronic mild stress (PNS) was used to evaluate the effects of PNS on fear extinction in adult offspring. The expression of hippocampal glycogen synthase kinase-3s (GSK-3α, β), N-methyl-d-aspartic acid receptors (NMDARs)-2B and the hippocampal cell proliferation in dentate gyrus in the adult offspring during fear extinction were studied. Our results showed that PNS significantly reduced body weight of pups, indicating PNS might induce growth retardation in offspring. Moreover, PNS significantly enhanced the freezing behavior of offspring at the phase of extinction, suggesting PNS impaired the abilities of fear extinction learning. In addition, PNS significantly increased the levels of GSK-3α, β and NR2B, but reduced hippocampal cell proliferation during fear extinction. Taken together, our findings suggest that maternal stress during pregnancy can impair the fear extinction of adult offspring, probably by affecting the neural plasticity of brain.

  11. HAIR CELL-LIKE CELL GENERATION INDUCED BY NATURE CULTURE OF ADULT RAT AUDITORY EPITHELIUM

    Institute of Scientific and Technical Information of China (English)

    Liu Hui; Zhu Hongliang; Li Shengli; Yao Xiaobao; Wang Xiaoxia

    2006-01-01

    Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial cells of adult rat were cultured. Immunocytochemistry and Bromodeoxyuridine (BrdU)labeling were used to detect properties and mitotic status of cultured cells. Results The cultured auditory epithelial cells showed a large, flat epithelial morphotype and expressed F-actin and cytokeratin, a subset of cells generated from auditory epithelium were labeled by calretinin, a specific marker of early hair cell. Conclusion Adult rat auditory epithelium can be induced to generate hair cell-like cells by nature culture, this phenomenon suggests that progenitor cells may exist in rat cochlea and they may give birth to new hair cells. Whether these progenitor cells are tissue specific stem cells is still need more study.

  12. Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

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    Hua Wang

    2015-01-01

    Full Text Available Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg for 35 days and those intragastrically administered phosphate buffered saline served as controls. The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups, in particular low-dose Lycium barbarum polysaccharides group, was significantly greater than that in the phosphate buffered saline group. Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein. These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype.

  13. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

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    Patricia eRivera

    2015-09-01

    Full Text Available Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10% or sucrose liquid diets for two weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+ and the replicating cell DNA marker 5-bromo-2’-deoxyuridine (BrdU+ in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ, subventricular zone of lateral ventricles (SVZ and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3±1.1 g/kg/day after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ and hypothalamus. The treatments (URB597, ACEA, JWH133 exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

  14. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    Science.gov (United States)

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  15. Effects of acute adult and early-in-life bladder inflammation on bladder neuropeptides in adult female rats

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    Ness Timothy J

    2011-08-01

    Full Text Available Abstract Background The purpose of the present study was to determine how acute adult and/or prior early-in life (EIL; P14-P16 exposure to bladder inflammation affects bladder content of calcitonin gene related peptide (CGRP and substance P (SP. Estrous cycle influences were also studied in the adult-treatment conditions. Methods In Experiment 1, intravesical zymosan or isoflurane anesthesia alone was administered to adult female rats. Bladders and serum were collected 24 hours later during each phase of the estrous cycle. In Experiment 2, zymosan or anesthesia alone was administered EIL and as adults, with bladder tissue collection 24 h later. Results In general, Experiment 1 showed that bladder content of both CGRP and SP was increased by inflammation. This effect was significant when data were collapsed across all phases of the estrous cycle, but was only significant during proestrus when individual comparisons were made during each phase of estrous. Also, adult bladder inflammation significantly reduced estradiol levels. In Experiment 2, bladder content of CGRP and SP was significantly increased in rats receiving EIL and/or adult inflammation. Bladder weights were also significantly increased by inflammation. Conclusions These data indicate that bladder CGRP and SP are maximally increased during the proestrus phase of the estrous cycle in inflamed adult female rats. EIL exposure to bladder inflammation alone can also produce an increase in CGRP and SP lasting into adulthood. Therefore, EIL experience with bladder inflammation may predispose an organism to experience a painful bladder disorder as an adult by increasing primary afferent content of CGRP and/or SP.

  16. Neuronal reorganization in adult rats neonatally exposed to (±-3,4-methylenedioxymethamphetamine

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    Michael T. Williams

    2014-01-01

    Full Text Available The abuse of methylenedioxymethamphetamine (MDMA during pregnancy is of concern. MDMA treatment of rats during a period of brain growth analogous to late human gestation leads to neurochemical and behavioral changes. MDMA from postnatal day (P11–20 in rats produces reductions in serotonin and deficits in spatial and route-based navigation. In this experiment we examined the impact of MDMA from P11 to P20 (20 mg/kg twice daily, 8 h apart on neuronal architecture. Golgi impregnated sections showed significant changes. In the nucleus accumbens, the dendrites were shorter with fewer spines, whereas in the dentate gyrus the dendritic length was decreased but with more spines, and for the entorhinal cortex, reductions in basilar and apical dendritic lengths in MDMA animals compared with saline animals were seen. The data show that neuronal cytoarchitectural changes are long-lasting following developmental MDMA exposure and are in regions consistent with the learning and memory deficits observed in such animals.

  17. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

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    U.S. Environmental Protection Agency — behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil. Electrophysiological...

  18. Zinc chelation reduces traumatic brain injury-induced neurogenesis in the subgranular zone of the hippocampal dentate gyrus.

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    Choi, Bo Young; Kim, Jin Hee; Kim, Hyun Jung; Lee, Bo Eun; Kim, In Yeol; Sohn, Min; Suh, Sang Won

    2014-10-01

    Numerous studies have demonstrated that traumatic brain injury (TBI) increases hippocampal neurogenesis in the rodent brain. However, the mechanisms underlying increased neurogenesis after TBI remain unknown. Continuous neurogenesis occurs in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) in the adult brain. The mechanism that maintains active neurogenesis in the hippocampal area is not known. A high level of vesicular zinc is localized in the presynaptic terminals of the SGZ (mossy fiber). The mossy fiber of dentate granular cells contains high levels of chelatable zinc in their terminal vesicles, which can be released into the extracellular space during neuronal activity. Previously, our lab presented findings indicating that a possible correlation may exist between synaptic zinc localization and high rates of neurogenesis in this area after hypoglycemia or epilepsy. Using a weight drop animal model to mimic human TBI, we tested our hypothesis that zinc plays a key role in modulating hippocampal neurogenesis after TBI. Thus, we injected a zinc chelator, clioquinol (CQ, 30mg/kg), into the intraperitoneal space to reduce brain zinc availability twice per day for 1 week. Neuronal death was evaluated with Fluoro Jade-B and NeuN staining to determine whether CQ has neuroprotective effects after TBI. The number of degenerating neurons (FJB (+)) and live neurons (NeuN (+)) was similar in vehicle and in CQ-treated rats at 1 week after TBI. Neurogenesis was evaluated using BrdU, Ki67 and doublecortin (DCX) immunostaining 1 week after TBI. The number of BrdU, Ki67 and DCX positive cell was increased after TBI. However, the number of BrdU, Ki67 and DCX positive cells was significantly decreased by CQ treatment. The present study shows that zinc chelation did not prevent neurodegeneration but did reduce TBI-induced progenitor cell proliferation and neurogenesis. Therefore, this study suggests that zinc has an essential role for modulating hippocampal

  19. Dentate Gyrus Local Circuit is Implicated in Learning Under Stress--a Role for Neurofascin.

    Science.gov (United States)

    Zitman, Femke M P; Lucas, Morgan; Trinks, Sabine; Grosse-Ophoff, Laura; Kriebel, Martin; Volkmer, Hansjürgen; Richter-Levin, Gal

    2016-03-01

    The inhibitory synapses at the axon initial segment (AIS) of dentate gyrus granular cells are almost exclusively innervated by the axo-axonic chandelier interneurons. However, the role of chandelier neurons in local circuitry is poorly understood and controversially discussed. The cell adhesion molecule neurofascin is specifically expressed at the AIS. It is crucially required for the stabilization of axo-axonic synapses. Knockdown of neurofascin is therefore a convenient tool to interfere with chandelier input at the AIS of granular neurons of the dentate gyrus. In the current study, feedback and feedforward inhibition of granule cells was measured in the dentate gyrus after knockdown of neurofascin and concomitant reduction of axo-axonic input. Results show increased feedback inhibition as a result of neurofascin knockdown, while feedforward inhibition remained unaffected. This suggests that chandelier neurons are predominantly involved in feedback inhibition. Neurofascin knockdown rats also exhibited impaired learning under stress in the two-way shuttle avoidance task. Remarkably, this learning impairment was not accompanied by differences in electrophysiological measurements of dentate gyrus LTP. This indicates that the local circuit may be involved in (certain types) of learning.

  20. Influence of rat substrain and growth conditions on the characteristics of primary cultures of adult rat spinal cord astrocytes.

    Science.gov (United States)

    Codeluppi, Simone; Gregory, Ebba Norsted; Kjell, Jacob; Wigerblad, Gustaf; Olson, Lars; Svensson, Camilla I

    2011-04-15

    Primary astrocyte cell cultures have become a valuable tool for studies of signaling pathways that regulate astrocyte physiology, reactivity, and function; however, differences in culture preparation affect data reproducibility. The aim of this work was to define optimal conditions for obtaining primary astrocytes from adult rat spinal cord with an expression profile most similar to adult human spinal cord astrocytes. Hence, we examined whether different Sprague-Dawley substrains and culture conditions affect astrocyte culture quality. Medium supplemented with fetal bovine serum from three sources (Sigma, Gibco, Hyclone) or a medium with defined composition (AM medium) was used to culture astrocytes isolated from spinal cords of adult Harlan and Charles River Spraque-Dawley rats. Purity was significantly different between cultures established in media with different sera. No microglia were detected in AM or Hyclone cultures. Gene expression was also affected, with AM cultures expressing the highest level of glutamine synthetase, connexin-43, and glutamate transporter-1. Interestingly, cell response to starvation was substrain dependent. Charles River-derived cultures responded the least, while astrocytes derived from Harlan rats showed a greater decrease in Gfap and glutamine synthetase, suggesting a more quiescent phenotype. Human and Harlan astrocytes cultured in AM media responded similarly to starvation. Taken together, this study shows that rat substrain and growth medium composition affect purity, expression profile and response to starvation of primary astrocytes suggesting that cultures of Harlan rats in AM media have optimal astrocyte characteristics, purity, and similarity to human astrocytes.

  1. Expression of the 5-HT receptors in rat brain during memory consolidation.

    Science.gov (United States)

    Meneses, A; Manuel-Apolinar, L; Rocha, L; Castillo, E; Castillo, C

    2004-07-09

    Serotonin (5-hydroxytryptamine, 5-HT) system displays more than 14 receptors subtypes on brain areas involved in learning and memory processes, and pharmacological manipulation of specific receptors selectively affects memory formation. In order to begin the search of 5-HT receptors expression during memory formation, in this work, we aimed to determine, by autoradiography (using 3H 5-HT as ligand, 2 nM, specific activity 123 Ci/mmol), 5-HT receptors (5-HTR) expression in passive (untrained) and autoshaping trained (3 sessions) adult (3 months) and old (9 months) male rats. Thus, trained adult rats had better retention than old animals. Raphe nuclei of adult and old trained rats expressed less receptors on medial and dorsal, respectively. Hippocampal CA1 area and dentate gyrus of adult trained rats expressed less 5-HTR, while dentate gyrus of old increased them. Basomedial amygdaloid nucleus in old trained rats expressed more 5-HTR; while in the basolateral amygdaloid nucleus they were augmented in both groups. Training decreased or did not change 5-HTR in caudate-putamen of adult or old animals. The above profile of 5-HTR expression is consistent with previous reports, and suggests that memory formation and aging modulates 5-HTR expression in brain areas relevant to memory systems.

  2. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    Science.gov (United States)

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  3. Effects of neonatal overfeeding on juvenile and adult feeding and energy expenditure in the rat.

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    Aneta Stefanidis

    Full Text Available Overfeeding during perinatal life leads to an overweight phenotype that persists throughout the juvenile stage and into adulthood, however, the mechanism(s underlying this effect are poorly understood. We hypothesized that obesity due to neonatal overfeeding is maintained by changes in energy expenditure and that these changes differ between males and females. We investigated feeding, physical activity, hormonal and metabolic alterations that occur in adult rats made obese by having been nursed in small litters (SL compared with those from control litters (CL. There were no differences in absolute food intake between the groups, and juvenile and adult SL rats ate less chow per gram body weight than the CL did in the dark (active phase. Juvenile, but not adult SL rats did have reduced whole body energy expenditure, but there were no differences between the groups by the time they reached adulthood. Adult SL females (but not males had reduced brown adipose tissue (BAT temperatures compared with CL in the first half of the dark phase. Our results indicate a persistent overweight phenotype in rats overfed as neonates is not associated with hyperphagia at any stage, but is reflected in reduced energy expenditure into the juvenile phase. The reduced dark phase BAT activity in adult SL females is not sufficient to reduce total energy expenditure at this stage of life and there is an apparently compensatory effect that prevents SL and CL from continuing to diverge in weight that appears between the juvenile and adult stages.

  4. Suspension of mitotic activity in dentate gyrus of the hibernating ground squirrel.

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    Popov, Victor I; Kraev, Igor V; Ignat'ev, Dmitri A; Stewart, Michael G

    2011-01-01

    Neurogenesis occurs in the adult mammalian hippocampus, a region of the brain important for learning and memory. Hibernation in Siberian ground squirrels provides a natural model to study mitosis as the rapid fall in body temperature in 24 h (from 35-36°C to +4-6°C) permits accumulation of mitotic cells at different stages of the cell cycle. Histological methods used to study adult neurogenesis are limited largely to fixed tissue, and the mitotic state elucidated depends on the specific phase of mitosis at the time of day. However, using an immunohistochemical study of doublecortin (DCX) and BrdU-labelled neurons, we demonstrate that the dentate gyrus of the ground squirrel hippocampus contains a population of immature cells which appear to possess mitotic activity. Our data suggest that doublecortin-labelled immature cells exist in a mitotic state and may represent a renewable pool for generation of new neurons within the dentate gyrus.

  5. Differentiation of embryonic versus adult rat neural stem cells into dopaminergic neurons in vitro

    Institute of Scientific and Technical Information of China (English)

    Chunlong Ke; Baili Chen; Shaolei Guo; Chao Yang

    2008-01-01

    BACKGROUND: It has been reported that the conversion of neural stem cells into dopaminergic neurons in vitro can be increased through specific cytokine combinations. Such neural stem cell-derived dopaminergic neurons could be used for the treatment of Parkinson's disease. However, little is known about the differences in dopaminergic differentiation between neural stem cells derived from adult and embryonic rats.OBJECTIVE: To study the ability of rat adult and embryonic-derived neural stem cells to differentiate into dopaminergic neurons in vitro.DESIGN: Randomized grouping design.SETTING: Department of Neurosurgery in the First Affiliated Hospital of Sun Yat-sen University.MATERIALS: This experiment was performed at the Surgical Laboratory in the First Affiliated Hospital of Sun Yat-scn University (Guangzhou, Guangdong, China) from June to December 2007. Eight, adult, male,Sprague Dawley rats and eight, pregnant, Sprague Dawley rats (embryonic day 14 or 15) were provided by the Experimental Animal Center of Sun Yat-sen University.METHODS: Neural stem cells derived from adult and embryonic rats were respectively cultivated in serum-free culture medium containing epidermal growth factor and basic fibroblast growth factor. After passaging, neural stem cells were differentiated in medium containing interleukin-1 ct, interleukin-11, human leukemia inhibition factor, and glial cell line-derived neurotrophic factor. Six days later, cells were analyzed by immunocytochemistry and flow cytometry.MAIN OUTCOME MEASURES: Alterations in cellular morphology after differentiation of neural stem cells derived from adult and embryonic rats; and percentage of tyrosine hydroxylase-positive neurons in the differentiated cells.RESULTS: Neural stem cells derived from adult and embryonic rats were cultivated in differentiation medium. Six days later, differentiated cells were immunoreactive for tyrosine hydroxylasc. The percentage of tyrosine hydroxylase positive neurons was (5.6 ± 2

  6. Polygalasaponin F induces long-term potentiation in adult rat hippocampus via NMDA receptor activation

    Institute of Scientific and Technical Information of China (English)

    Feng SUN; Jian-dong SUN; Ning HAN; Chuang-jun LI; Yu-he YUAN; Dong-ming ZHANG; Nai-hong CHEN

    2012-01-01

    Aim:To investigate the effect and underlying mechanisms of polygalasaponin F (PGSF),a triterpenoid saponin isolated from Polygala japonica,on long-term potentiation (LTP)in hippocampus dentate gyrus (DG)of anesthetized rats.Methods:Population spike (PS)of hippocampal DG was recorded in anesthetized male Wistar rats.PGSF,the NMDAR inhibitor MK801 and the CaMKll inhibitor KN93 were intracerebroventricularly administered.Western blotting analysis was used to examine the phosphorylation expressions of NMDA receptor subunit 2B (NR2B),Ca2+/calmodulin-dependent kinase Ⅱ (CaMKII),extracellular signalregulated kinase (ERK),and cAMP response element-binding protein (CREB).Results:Intracerebroventricular administration of PGSF (1 and 10 μmol/L)produced long-lasting increase of PS amplitude in hippocampal DG in a dose-dependent manner.Pre-injection of MK801 (100 μmol/L)or KN93 (100 μmol/L)completely blocked PGSFinduced LTP.Furthermore,the phosphorylation of NR2B,CaMKII,ERK,and CREB in hippocampus was significantly increased 5-60min after LTP induction.The up-regulation of p-CaMKII expression could be completely abolished by pre-injection of MK801.The upregulation of p-ERK and p-CREB expressions could be partially blocked by pre-injection of KN93.Conclusion:PGSF could induce LTP in hippocampal DG in anesthetized rats via NMDAR activation mediated by CaMKII,ERK and CREB signaling pathway.

  7. Exercise improves cognitive responses to psychological stress through enhancement of epigenetic mechanisms and gene expression in the dentate gyrus.

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    Andrew Collins

    Full Text Available BACKGROUND: We have shown previously that exercise benefits stress resistance and stress coping capabilities. Furthermore, we reported recently that epigenetic changes related to gene transcription are involved in memory formation of stressful events. In view of the enhanced coping capabilities in exercised subjects we investigated epigenetic, gene expression and behavioral changes in 4-weeks voluntarily exercised rats. METHODOLOGY/PRINCIPAL FINDINGS: Exercised and control rats coped differently when exposed to a novel environment. Whereas the control rats explored the new cage for the complete 30-min period, exercised animals only did so during the first 15 min after which they returned to sleeping or resting behavior. Both groups of animals showed similar behavioral responses in the initial forced swim session. When re-tested 24 h later however the exercised rats showed significantly more immobility behavior and less struggling and swimming. If rats were killed at 2 h after novelty or the initial swim test, i.e. at the peak of histone H3 phospho-acetylation and c-Fos induction, then the exercised rats showed a significantly higher number of dentate granule neurons expressing the histone modifications and immediate-early gene induction. CONCLUSIONS/SIGNIFICANCE: Thus, irrespective of the behavioral response in the novel cage or initial forced swim session, the impact of the event at the dentate gyrus level was greater in exercised rats than in control animals. Furthermore, in view of our concept that the neuronal response in the dentate gyrus after forced swimming is involved in memory formation of the stressful event, the observations in exercised rats of enhanced neuronal responses as well as higher immobility responses in the re-test are consistent with the reportedly improved cognitive performance in these animals. Thus, improved stress coping in exercised subjects seems to involve enhanced cognitive capabilities possibly resulting from

  8. Morphological alterations in newly born dentate gyrus granule cells that emerge after status epilepticus contribute to make them less excitable.

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    Julián Tejada

    Full Text Available Computer simulations of external current stimulations of dentate gyrus granule cells of rats with Status Epilepticus induced by pilocarpine and control rats were used to evaluate whether morphological differences alone between these cells have an impact on their electrophysiological behavior. The cell models were constructed using morphological information from tridimensional reconstructions with Neurolucida software. To evaluate the effect of morphology differences alone, ion channel conductances, densities and distributions over the dendritic trees of dentate gyrus granule cells were the same for all models. External simulated currents were injected in randomly chosen dendrites belonging to one of three different areas of dentate gyrus granule cell molecular layer: inner molecular layer, medial molecular layer and outer molecular layer. Somatic membrane potentials were recorded to determine firing frequencies and inter-spike intervals. The results show that morphologically altered granule cells from pilocarpine-induced epileptic rats are less excitable than control cells, especially when they are stimulated in the inner molecular layer, which is the target area for mossy fibers that sprout after pilocarpine-induced cell degeneration. This suggests that morphological alterations may act as a protective mechanism to allow dentate gyrus granule cells to cope with the increase of stimulation caused by mossy fiber sprouting.

  9. Isoflavones prevent bone loss following ovariectomy in young adult rats

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    Chen Li-Ting

    2008-03-01

    Full Text Available Abstract Soy protein, a rich source of phytoestrogens, exhibit estrogen-type bioactivity. The purpose of this study was to determine if ingestion of isoflavones before ovariectomy can prevent bone loss following ovariectomy. Twenty-four nulliparous Wistar rats were randomly divided into four groups. In the normal diet groups, a sham operation was performed on Group A, while ovariectomy was performed on Group B. For Groups C and D, all rats were fed with an isoflavone-rich (25 mg/day diet for one month, then bilateral ovariectomy were performed. In the rats in Group C, a normal diet was begun following the ovariectomy. The rats in Groups D continued to receive the isoflavone-rich diet for two additional months postoperatively. All rats were sacrificed 60 days after surgery. The weight of bone ash of the long bones and whole lumbar spine were determined. A histological study of cancellous bone was done and biochemical indices of skeletal metabolism were performed and analyzed. The markers of bone metabolism exhibited no significant changes. When compared with the sham-operated rats fed a normal diet, the bone mass of ovariectomized rats decreased significantly; pre-ovariectomy ingestion of an isoflavone-rich diet did not prevent bone loss. The bone mass of rats treated with an isoflavone-rich diet for three months was higher than controls two months after ovariectomy. Dietary isoflavones did not prevent the development of post-ovariectomy bone loss, but long-term ingestion of an isoflavone-rich diet increased the bone mineral contents after ovariectomy in young rats.

  10. Morphine treatment during juvenile isolation increases social activity and opioid peptides release in the adult rat.

    Science.gov (United States)

    Van den Berg, C L; Kitchen, I; Gerrits, M A; Spruijt, B M; Van Ree, J M

    1999-05-29

    The consequences of juvenile isolation and morphine treatment on general activity, social activity and endogenous opioid release during a social interaction test were investigated in the adult rat. Rats were either isolated or socially housed during weeks 4 and 5 of age and treated daily during this isolation period subcutaneously with either saline or morphine. Directly after a social interaction test at 10 weeks of age, rats were injected with [3H]-diprenorphine and subsequently prepared for in vivo autoradiography. The autoradiographic technique was used to visualise neuroanatomical changes in opioid receptor occupancy, probably reflecting changes in opioid peptide release, as a result of social activity. Juvenile isolation increased general activity during the social interaction test, an effect which was accompanied by a reduction of opioid receptor occupancy in many brain areas, suggesting an increased opioid peptide release as a consequence of socially-induced general activity. Morphine treatment in isolated rats caused an increase in adult social activity and enhanced opioid peptide release in some cortical regions and the ventral tegmental area as compared to saline treated rats. Both social activity and opioid receptor occupancy were unaffected by morphine treatment in non-isolated rats. The present study underscores the role of opioid systems in adult social behaviors as a consequence of juvenile isolation. The results suggest a relationship between social activity and opioid peptide release during social contact. Increased social activity seems to be accompanied by elevated opioid peptide release in distinct brain areas after morphine treatment during juvenile isolation.

  11. Effect of lindane on antioxidant enzymes in epididymis and epididymal sperm of adult rats

    Institute of Scientific and Technical Information of China (English)

    K.C. Chitra; R. Sujatha; C. Latchoumycandane; P.P. Mathur

    2001-01-01

    Aim: To find out the changes induced by lindane on the antioxidant enzymes in epididymis and epididymal sperm of adult rats, Methods; Adult male rats were orally administered lindane at a dose of 5.0 mg/kg body weight per day for 30 days. At the end of the treatment, the rats were sacrificed. The epididymis was removed and weighed and sperm were collected for sperm count, motility and biochemical studies. A 1% homogenate of epididymis was prepared and used for biochemical estimations. Results: In lindane-treated rats, there were significant reductions in the epididymal weight, epididymal sperm count and motility compared with the controls. Significant decreases in the superoxide dismutase (SOD), catalase, glutathione reductase and glutathione peroxidase activities and significant increases in the H2O2 generation and lipid peroxidation were also observed in the epididymis and epididymal sperm of lindane-treated rats. Conclusion: Lindane decreases the levels of antioxidant enzymes in the epididymis and epididymal sperm of adult rats thereby inducing oxidative stress.

  12. Early treatment with metformin induces resistance against tumor growth in adult rats.

    Science.gov (United States)

    Trombini, Amanda B; Franco, Claudinéia Cs; Miranda, Rosiane A; de Oliveira, Júlio C; Barella, Luiz F; Prates, Kelly V; de Souza, Aline A; Pavanello, Audrei; Malta, Ananda; Almeida, Douglas L; Tófolo, Laize P; Rigo, Kesia P; Ribeiro, Tatiane As; Fabricio, Gabriel S; de Sant'Anna, Juliane R; Castro-Prado, Marialba Aa; de Souza, Helenir Medri; de Morais, Hely; Mathias, Paulo Cf

    2015-01-01

    It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer.

  13. [Disruption of latent inhibition in adult rats after prepubertal dopamine terminals lesions in the ventral hippocampus].

    Science.gov (United States)

    Loskutova, L V; Kostiunina, N V; Red'kina, A V

    2010-05-01

    Wistar rats were submitted to bilateral ventral hippocampal injection of 6-hydroxydopamine on 32nd day after birth. Latent inhibition was measured in passive or active avoidance tasks when the rats received 20 and 100 pre-exposures of conditioned stimulus. Prepubertal and adult lesioned rats showed a deficit in the latent inhibition but not in the capacity to avoidance learning in presence of the conditioned stimulus novelty. Possible mechanism of the involvement of hippocampal dopaminergic terminals in attention inhibition to irrelevant information is considered.

  14. Synaptic kainate receptors in interplay with INaP shift the sparse firing of dentate granule cells to a sustained rhythmic mode in temporal lobe epilepsy.

    Science.gov (United States)

    Artinian, Julien; Peret, Angélique; Marti, Geoffrey; Epsztein, Jérôme; Crépel, Valérie

    2011-07-27

    Dentate granule cells, at the gate of the hippocampus, use coincidence detection of synaptic inputs to code afferent information under a sparse firing regime. In both human patients and animal models of temporal lobe epilepsy, mossy fibers sprout to form an aberrant glutamatergic network between dentate granule cells. These new synapses operate via long-lasting kainate receptor-mediated events, which are not present in the naive condition. Here, we report that in chronic epileptic rat, aberrant kainate receptors in interplay with the persistent sodium current dramatically expand the temporal window for synaptic integration. This introduces a multiplicative gain change in the input-output operation of dentate granule cells. As a result, their sparse firing is switched to an abnormal sustained and rhythmic mode. We conclude that synaptic kainate receptors dramatically alter the fundamental coding properties of dentate granule cells in temporal lobe epilepsy.

  15. Hippocampal plasticity after a vagus nerve injury in the rat

    Institute of Scientific and Technical Information of China (English)

    Giulia Ronchi; Vitaly Ryu; ong ling; Krzysztof Czaja

    2012-01-01

    Stimulation of the vagus nerve has been previously reported to promote neural plasticity and neurogenesis in the brain. Several studies also revealed plastic changes in the spinal cord after injuries to somatosensory nerves originating from both the brachial and lumbo-sacral plexuses. However, the neurogenic responses of the brain to the injury of the viscerosensory innervation are not as yet well understood. In the present study, we investigated whether cells in the dentate gyrus of the hippocampus respond to a chemical and physical damage to the vagus nerve in the adult rat. Intraperitoneal capsaicin administration was used to damage non-myelinated vagal afferents while subdiaphragmatic vagotomy was used to damage both the myelinated and non-myelinated vagal afferents. The 5-bromo-2-deoxyuridine (BrdU) incorporation together with cell-specific markers was used to study neural proliferation in subgranular zone, granule cell layer, molecular layer and hilus of the dentate gyrus. Microglia activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter-binding molecule 1. Results revealed that vagotomy decreased BrdU incorporation in the hilus 15 days after injury compared to the capsaicin group. Capsaicin administration decreased BrdU incorporation in the granular cell layer 60 days after the treatment. Capsaicin decreased the number of doublecortin-expressing cells in the dentate gyrus, whereas vagotomy did not alter the expression of doublecortin in the hippocampus. Both the capsaicin- and the vagotomy-induced damage to the vagus nerve decreased microglia activation in the hippocampus at 15 days after the injury. At 30 days post injury, capsaicin-treated and vagotomized rats revealed significantly more activated microglia. Our findings show that damage to the subdiaphragmatic vagus in adult rats is followed by microglia activation and long-lasting changes in the dentate gyrus

  16. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V

    2012-01-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

  17. HISTOLOGICAL STUDIES OF THE EFFECTS OF RED PEPPER ON THE STOMACH OF ADULT WISTAR RATS

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    Josiah O. Adjene

    2007-01-01

    Full Text Available Histological effects of red pepper commonly used as spice in food on the stomach of adult wistar rats were carefully investigated. The rats of both sexes (n=24, average weight of 200g were randomly assigned into two treatments (n=16 and control (n=6 groups. The rats in the treatments groups received 1g and 2g of red pepper thoroughly mixed with 20g of their feeds for 7 and 14 days, while the control rats received equal amounts of feeds without the red pepper added. The rats were fed with grower's mash purchased from Edo feeds and flour mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day eight and fifteen of the experiment respectively.The stomach was carefully dissected out and quickly fixed in 10% formol saline for routine histological procedure after H & E method.The histological findings after H&E methods indicated that the treated sections of the stomach showed some level of cellular hypertrophy, congestion of blood vessels degenerative changes disruption and distortion of the cytoarchitecture of the stomach.These findings indicate that red pepper may have some deleterious effects on the microanatomy of the stomach of adult wistar rat at higher doses. It is recommended that further studies aimed at corroborating these findings be carried out.

  18. HISTOLOGICAL STUDIES OF THE EFFECTS OF MONOSODIUM GLUTAMATE ON THE INFERIOR COLLICULUS OF ADULT WISTAR RATS.

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    A.O. Eweka.

    2008-01-01

    Full Text Available Histological effects of Monosodium glutamate (MSG commonly used as food additive on the inferior colliculus (IC of adult Wistar rats were carefully studied. The rats of both sexes (n=24, average weight of 185g were randomly assigned into two treatments (n=16 and control (n=8 groups. The rats in the treatment groups received 3g and 6g of MSG thoroughly mixed with their feeds for fourteen days, while the control rats received equal amounts of feeds without MSG added. The rats were fed with growers' mash purchased from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The inferior colliculus was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method.The histological findings after H&E methods indicated that the treated sections of the inferior colliculus showed some cellular degenerative changes, cellular hypertrophy, and autophagic vacuoles with some intercellular vacuolations appearing in the stroma, and some degree of neuronal hypertrophy when compared to the control sections.These findings indicate that MSG consumption may have a deleterious effect on the neurons of the inferior colliculus (IC. MSG may probably have adverse effects on the auditory sensibilities by its deleterious effects on the nerve cells of the IC of adult Wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

  19. Histological effects of chronic consumption of soda pop drinks on kidney of adult Wister rats

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    Josiah Obaghwarhievwo Adjene

    2010-05-01

    Full Text Available Background: Health concerns over soda pop drinks have been severally report. However, histological perspectives are not very common. Aim: The objective of this study is to investigate histological effect of chronic consumption of soda pop drinks on the kidney of adult Wistar rats. Materials and methods: The rats of both sexes (n = 24, with average weight of 200g were randomly assigned into two treatment (A & B (n=16 and Control (c (n=8 groups. The rats in the treatment group (A received a brand of soda pop drink on a daily basis for thirty days. The rats in treatment group (B received another brand of soda drink, while the control group (C received equal amount of water for the same period. The rats were given the drinks as well as feeds liberally for thirty days, and sacrificed by cervical dislocation on the thirty-first day of the experiment. The kidney was carefully dissected out and quickly fixed in 10% formal saline for histological study. Results: The findings indicate that rats in the treated groups (A&B showed some varying degree of distortion and disruption of the renal structure. There are observable diffuse signs of glomerulonephritis with some congestion and tubular necrosis as compared to the control group. Conclusion: Chronic consumption of soda pop drinks may affect the microanatomy of the kidney of adult Wistar rats. Further study aimed at corroborating these observations in humans is warranted.

  20. Histological effects of chronic consumption of soda pop drinks on kidney of adult Wister rats

    Directory of Open Access Journals (Sweden)

    Josiah Obaghwarhievwo Adjene

    2010-01-01

    Full Text Available Background : Health concerns over soda pop drinks have been severally report. However, histological perspectives are not very common. Aim: The objective of this study is to investigate histological effect of chronic consumption of soda pop drinks on the kidney of adult Wistar rats. Materials and methods : The rats of both sexes (n = 24, with average weight of 200g were randomly assigned into two treatment (A & B (n=16 and Control (c (n=8 groups. The rats in the treatment group (A received a brand of soda pop drink on a daily basis for thirty days. The rats in treatment group (B received another brand of soda drink, while the control group (C received equal amount of water for the same period. The rats were given the drinks as well as feeds liberally for thirty days, and sacrificed by cervical dislocation on the thirty-first day of the experiment. The kidney was carefully dissected out and quickly fixed in 10% formal saline for histological study. Results : The findings indicate that rats in the treated groups (A&B showed some varying degree of distortion and disruption of the renal structure. There are observable diffuse signs of glomerulonephritis with some congestion and tubular necrosis as compared to the control group. Conclusion : Chronic consumption of soda pop drinks may affect the microanatomy of the kidney of adult Wistar rats. Further study aimed at corroborating these observations in humans is warranted.

  1. HISTOLOGICAL EFFECTS OF CHRONIC CONSUMPTION OF NUTMEG ON THE LATERAL GENICULATE BODY OF ADULT WISTAR RATS.

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    J.O. Adjene

    2010-01-01

    Full Text Available The effects of chronic consumption of nutmeg commonly used as a spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the lateral geniculate body of adult wistar rats was studied.The rats of both sexes, with average weight of 200g were randomly assigned into treatment and control groups. The rats in the treatment group (n=8 received 2g of nutmeg thoroughly mixed with the feeds on a daily basis for thirty-two days. The control group (n=8 received equal amount of feeds daily without nutmeg added for thirty-two days. The growers mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo State, Nigeria and the rats were given water liberally. The rats were sacrificed on the thirty-three day of the experiment. The lateral geniculate body was carefully dissected out and quickly fixed in 10% formal saline for histological study.The findings indicate that rats in the treated group showed some cellular degenerative changes like sparse cellular population, pyknotic nuclei with some microcystic changes, edema and vacuolations in the stroma of the treated lateral geniculate body as compared to that of the control group.Chronic consumption of nutmeg may therefore have an adverse effect on the visual sensibilities by affecting the microanatomy of the lateral geniculate body of adult wistar rats. It is recommended for further studies aimed at corroborating these observations.

  2. Neonatal sensory deprivation promotes development of absence seizures in adult rats with genetic predisposition to epilepsy.

    Science.gov (United States)

    Sitnikova, Evgenia

    2011-03-04

    Absence epilepsy has age-related onset. In a WAG/Rij rat genetic model, absence seizures appear after puberty and they are increased with age. It is known that (1) epileptic activity in WAG/Rij rats is initiated at the perioral area in the somatosensory cortex; (2) sensory deprivation, i.e., whisker trimming during the critical period of development, could enhance excitatory activity in the somatosensory cortex. It is hypothesized that the cortex may become more excitable after neonatal vibrissae removal, and this may precipitate absence seizures in adult rats. We found that whisker trimming during the first postnatal weeks caused more rapid development of EEG seizure activity in adult WAG/Rij rats. Epileptic discharges in the trimmed rats were more numerous (vs control), showed longer duration and often appeared in desynchronized and drowsy EEG. The number of absence-like spindle-shaped EEG events (spike-wave spindles) in the whisker-trimmed rats was higher than in control, especially during the intermediate sleep state. An age-dependent increase of intermediate sleep state was found in the trimmed rats, but not in the intact animals. We discuss epigenetic factors that can modulate absence epilepsy in genetically prone subjects.

  3. Neurons of the dentate molecular layer in the rabbit hippocampus.

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    Francisco J Sancho-Bielsa

    Full Text Available The molecular layer of the dentate gyrus appears as the main entrance gate for information into the hippocampus, i.e., where the perforant path axons from the entorhinal cortex synapse onto the spines and dendrites of granule cells. A few dispersed neuronal somata appear intermingled in between and probably control the flow of information in this area. In rabbits, the number of neurons in the molecular layer increases in the first week of postnatal life and then stabilizes to appear permanent and heterogeneous over the individuals' life span, including old animals. By means of Golgi impregnations, NADPH histochemistry, immunocytochemical stainings and intracellular labelings (lucifer yellow and biocytin injections, eight neuronal morphological types have been detected in the molecular layer of developing adult and old rabbits. Six of them appear as interneurons displaying smooth dendrites and GABA immunoreactivity: those here called as globoid, vertical, small horizontal, large horizontal, inverted pyramidal and polymorphic. Additionally there are two GABA negative types: the sarmentous and ectopic granular neurons. The distribution of the somata and dendritic trees of these neurons shows preferences for a definite sublayer of the molecular layer: small horizontal, sarmentous and inverted pyramidal neurons are preferably found in the outer third of the molecular layer; vertical, globoid and polymorph neurons locate the intermediate third, while large horizontal and ectopic granular neurons occupy the inner third or the juxtagranular molecular layer. Our results reveal substantial differences in the morphology and electrophysiological behaviour between each neuronal archetype in the dentate molecular layer, allowing us to propose a new classification for this neural population.

  4. The role of the dorsal dentate gyrus in object and object-context recognition.

    Science.gov (United States)

    Dees, Richard L; Kesner, Raymond P

    2013-11-01

    The aim of this study was to determine the role of the dorsal dentate gyrus (dDG) in object recognition memory using a black box and object-context recognition memory using a clear box with available cues that define a spatial context. Based on a 10 min retention interval between the study phase and the test phase, the results indicated that dDG lesioned rats are impaired when compared to controls in the object-context recognition test in the clear box. However, there were no reliable differences between the dDG lesioned rats and the control group for the object recognition test in the black box. Even though the dDG lesioned rats were more active in object exploration, the habituation gradients did not differ. These results suggest that the dentate gyrus lesioned rats are clearly impaired when there is an important contribution of context. Furthermore, based on a 24 h retention interval in the black box the dDG lesioned rats were impaired compared to controls.

  5. Uterine phenotype of young adult rats exposed to dietary soy or genistein during development.

    Science.gov (United States)

    Eason, Renea R; Till, S Reneé; Velarde, Michael C; Geng, Yan; Chatman, Leon; Gu, Liwei; Badger, Thomas M; Simmen, Frank A; Simmen, Rosalia C M

    2005-10-01

    Dietary soy intake is associated with protection from breast cancer, but questions persist on the potential risks of the major soy isoflavone genistein (GEN) on female reproductive health. Here, we evaluated intermediate markers of cancer risk in uteri of cycling, young adult Sprague-Dawley rats lifetime exposed to one of three AIN-93G semipurified diets: casein (CAS), soy protein isolate (SPI+ with 276 mg GEN aglycone equivalents/kg) and CAS+GEN (GEN at 250 mg/kg). Postnatal day 50 (PND50) rats lifetime exposed to GEN or SPI+ had similar uterine luminal epithelium height, myometrial thickness, endometrial gland numbers, endometrial immunoreactive proliferating cell nuclear antigen (PCNA), and serum estrogen and progesterone, as CAS-fed rats. GEN-fed rats showed modestly increased apoptosis in uterine glandular epithelium, compared to those of CAS- or SPI+-fed groups. Diet had no effect on the uterine expression of genes for the tumor suppressors PTEN, p53 and p21, and the apoptotic-associated proteins Bcl2, Bax and progesterone receptor. Uterine tissue and serum concentrations of total GEN were higher in rats fed GEN than in those fed SPI+. Human Ishikawa endocarcinoma cells treated with GEN-fed rat serum tended to exhibit increased apoptotic status than those treated with CAS-fed rat serum. Exogenously added GEN (0.2 and 2 microM) increased, while estradiol-17beta (0.1 microM) decreased Ishikawa cell apoptosis, relative to untreated cells. Results suggest that lifetime dietary exposure to soy foods does not alter uterine cell phenotype in young adult rats, while GEN, by enhancing uterine endometrial glandular apoptosis in vivo and in vitro, may confer protection against uterine carcinoma. Given its limited influence on uterine phenotype of young adult females, GEN, when taken as part of soy foods or as supplement, should be favorably considered for other potential health benefits.

  6. Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

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    Lu Kong

    2014-11-01

    Full Text Available Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH and luteinizing hormone (LH, and lowered etradiol (E2 serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.

  7. EFFECTS OF CEREBRAL CORTICAL CONCIS ON CELL PROLIFERATION OF THE SUBVENTRICULAR ZONE IN ADULT RATS

    Institute of Scientific and Technical Information of China (English)

    Zhang Yuelin; Qiu Shudong; Zhang Pengbo; Shi Wei

    2006-01-01

    Objective To investigate the proliferative response and time course of endogenous neural stem/progenitor cells after cerebral cortical concis in the adult rats. Methods Eighty adult male Sprague-Dawley rats were used in this study. Cumulative BrdU labeling was employed to detect the proliferating cells. At 1 d, 3 d, 7 d, 14 d, and 21 d after cerebral cortical concis, the rats were killed for BrdU immunohistochemical staining and cell counting in the injured ipsilateral SVZ. Results Little BrdU immunoreactivity cells was present in SVZ of the control rats from day 7 to day 21 after sham operation. The number of BrdU immunoreactivity cells in the injured ipsilateral SVZ increased at day 1 and peaked at day 7 after cerebral cortical concis. Conclusion After cerebral cortical concis of the adult rats, neural stem/progenitor cells in the injured ipsilateral SVZ markedly proliferated with a peak at day 7. This finding may be important for manipulating SVZ cells to promote the recovery from cerebral cortical concis.

  8. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats.

    Science.gov (United States)

    Holtz, Nathan A; Carroll, Marilyn E

    2015-06-01

    Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability.

  9. Effect of lindane on testicular antioxidant system and steroidogenic enzymes in adult rats

    Institute of Scientific and Technical Information of China (English)

    R. Sujatha; K.C. Chitin; C. Latchoumycandane; P.P. Mathur

    2001-01-01

    Aim: To find out the effect of lindane on testicular antioxidant system and testicular steroidogenesis in adult male rats. Methods: Adult male rats were orally administered with lindane at a dose of 5.0 mg/kg body weight per day for 30 days. Twenty-four hours after the last treatment the rats were killed using anesthetic ether. Testes, epididymis,seminal vesicles and ventral prostate were removed and weighed. A 10% testicular homogenate was prepared and cen trifuged at 4°C. The supematant was used for various biochemical estimations. Results: The body weight and the weights of testes, epididymis, seminal vesicles and ventral prostate were reduced in lindane-treated rars. There was asignificant decline in the activities of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione reduc tase while an increase in hydrogen peroxide (H2O2) generation was observed. The specific activities of testicular steroidogenic enzymes 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were decreased. The levels of DNA, RNA and protein were also decreased in lindane-treated rats. Conclusion: Lindane induces oxida tive stress and decreases antioxidant enzymes in adult male rats.

  10. Prenatal Choline Availability Alters the Context Sensitivity of Pavlovian Conditioning in Adult Rats

    Science.gov (United States)

    Lamoureux, Jeffrey A.; Meck, Warren H.; Williams, Christina L.

    2008-01-01

    The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3-4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline…

  11. Positron emission tomography for serial imaging of the contused adult rat spinal cord.

    NARCIS (Netherlands)

    Nandoe, R.D.S.; Yu, J.; Seidel, J.; Rahiem, S.T.; Hurtado, A.; Tsui, B.M.; Grotenhuis, J.A.; Pomper, M.G.; Oudega, M.

    2010-01-01

    We investigated whether small-animal positron emission tomography (PET) could be used in combination with computed tomography (CT) imaging techniques for longitudinal monitoring of the injured spinal cord. In adult female Sprague-Dawley rats (n = 6), the ninth thoracic (T9) spinal cord segment was e

  12. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    Science.gov (United States)

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  13. The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

    Science.gov (United States)

    Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

    2015-01-01

    The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

  14. Monitoring of intermittent PTH(1-34) treatment by serum PINP in adult ovariectomized osteopenic rats

    DEFF Research Database (Denmark)

    Halleen, Jussi; Peng, ZhiQi; Fagerlund, Katja

    , allowing measurement of serum PINP in preclinical rodent osteoporosis models. The purpose of this study was to evaluate the use of serum PINP for monitoring intermittent PTH(1-34) treatment in adult ovariectomized (OVX) osteopenic rats. Study groups included a sham-operated control group and an OVX...

  15. Reinnervation of muscles after transection of the sciatic nerve in adult rats

    NARCIS (Netherlands)

    Ijkema-Paassen, J; Meek, MF; Gramsbergen, A

    2002-01-01

    Functional recovery after transection of the sciatic nerve in adult rats is poor, probably because of abnormalities in reinnervation. Denervation and reinnervation patterns were studied morphologically in the lateral gastrocnemius (LGC), tibialis anterior (TA), and soleus (SOL) muscles for 21 weeks

  16. Peripheral effect of NMDA receptor antagonists on adult rats exposed to neonatal colon pain

    Institute of Scientific and Technical Information of China (English)

    ChunLin; ElieD.Al-Chaer

    2004-01-01

    AIM: Previous work done by Al-Chaer' s lab has shown that colon irritation (CI) in neonates can lead to chronic visceral hypersensitivity in adult rats, with characteristics of visceral allodynia and hyperalgesia, associated with central neuronal sensitization in the absence of identifiable peripheral pathology (Al-Chaer et al. 2000) . The pathogenesis of

  17. Strain differences in baroceptor reflex in adult Wistar Kyoto rats

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    Vitor E. Valenti

    2010-01-01

    Full Text Available OBJECTIVES: A subset of normotensive Sprague-Dawley rats show lower baroreflex sensitivity; however, no previous study investigated whether there are differences in baroreflex sensitivity within this subset. Our study compared baroreflex sensitivity among conscious rats of this specific subtype. METHODS: Male Wistar Kyoto (WKY rats (16 weeks old were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure (MAP and heart rate (HR. Baroreflex gain was calculated as the ratio between change in HR and MAP variation (ΔHR/ΔMAP in response to a depressor dose of sodium nitroprusside (SNP, 50 µg/kg, i.v. and a pressor dose of phenylephrine (PE, 8 µg/kg, i.v.. Rats were divided into four groups: 1 low bradycardic baroreflex (LB, baroreflex gain (BG between -1 and -2 bpm/mmHg tested with PE; 2 high bradycardic baroreflex (HB, BG < -2 bpm/mmHg tested with PE; 3 low tachycardic baroreflex (LT, BG between -1 and -2 bpm/mmHg tested with SNP and; 4 high tachycardic baroreflex (HT, BG < -2 bpm/mmHg tested with SNP. Significant differences were considered for p < 0.05. RESULTS: Approximately 37% of the rats showed a reduced bradycardic peak, bradycardic reflex and decreased bradycardic gain of baroreflex while roughly 23% had a decreased basal HR, tachycardic peak, tachycardic reflex and reduced sympathetic baroreflex gain. No significant alterations were noted with regard to basal MAP. CONCLUSION: There is variability regarding baroreflex sensitivity among WKY rats from the same laboratory.

  18. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    Science.gov (United States)

    Oosthuizen, M K; Amrein, I

    2016-06-02

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species.

  19. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    Science.gov (United States)

    Newson, Penny N; van den Buuse, Maarten; Martin, Sally; Lynch-Frame, Ann; Chahl, Loris A

    2014-10-01

    Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

  20. The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

    Science.gov (United States)

    Antuschevich, H; Kapica, M; Krawczynska, A; Herman, A; Kato, I; Kuwahara, A; Zabielski, R

    2016-06-01

    Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion.

  1. Body and Testicular Weight Changes in Adult Wistar Rats Following Oral Administration of Artesunate

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    al-hassan m. izunya

    2010-05-01

    Full Text Available This experiment was designed to study the effects on the body and testicular weights of adult wistar rats that recieved an oral administration of normal and double normal doses of artesunate. The rats were divided into three groups (A, B and C of five rats each. A and B served as the treatment groups, while C served as the control group. Group A rats were given 4mg.kg-1 b.w of artesunate daily for 3 days followed by 2mg.kg-1 b.w daily for next for 4 days. Group B rats were given 8mg.kg-1 b.w of artesunate daily for 3 days followed by 4mg.kg-1 b.w daily for next 4 days, while group C rats were given only distilled water. The rats were fed with grower's mash purchased from Edo feeds and Flour Mill Ltd, Ewu, Edo state and were given w ater ad libitum. On day eight of the experiment, the rats were weighed and sacrificed. The testes w ere carefully dissected out, freed from adherent tissues and weighed to the nearest 0.001 g. The results showed no changes in body weight of rats in groups A, B and C. There was also no significant change in testicular weight of rats in group A. However a significant increase in testicular weight was observed in group C. Our results suggest that artesunate at normal and double normal doses, has no effect on body weight of rats but may be toxic to the testes at higher doses. It is uncertain however if these changes are reversible. It is recommended therefore, that further studies aimed at corroborating these observations be carried out.

  2. Dermal penetration of [14C]captan in young and adult rats.

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    Fisher, H L; Hall, L L; Sumler, M R; Shah, P V

    1992-07-01

    Age dependence in dermal absorption has been a major concern in risk assessment. Captan, a chloroalkyl thio heterocyclic fungicide, was selected for study of age dependence as representative of this class of pesticides. Dermal penetration of [14C]captan applied at 0.286 mumol/cm2 was determined in young (33-d-old) and adult (82-d-old) female Fischer 344 rats in vivo and by two in vitro methods. Dermal penetration in vivo at 72 h was about 9% of the recovered dose in both young and adult rats. The percentage penetration was found to increase as dosage (0.1, 0.5, 2.7 mumol/cm2) decreased. Two in vitro methods gave variable dermal penetration values compared with in vivo results. A static system yielded twofold higher dermal penetration values compared with in vivo results for both young and adult rats. A flow system yielded higher dermal penetration values in young rats and lower penetration values in adults compared with in vivo results. Concentration in body, kidney, and liver was less in young than in adult rats given the same absorbed dosage. A physiological pharmacokinetic model was developed having a dual compartment for the treated skin and appeared to describe dermal absorption and disposition well. From this model, tissue/blood ratios of captan-derived radioactivity for organs were found to range from 0.35 to 3.4, indicating no large uptake or binding preferences by any organ. This preliminary pharmacokinetic model summarizes the experimental findings and could provide impetus for more complex and realistic models.

  3. Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats.

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    Lozano, German; Elmaghrabi, Ayah; Salley, Jordan; Siddique, Khurrum; Gattineni, Jyothsna; Baum, Michel

    2015-03-01

    The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min(-1)·100 g body wt(-1) in the 20% group (P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min(-1)·100 g body wt(-1), which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min(-1)·100 g body wt(-1)). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing.

  4. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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    Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

    2011-11-18

    Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  5. Ontogeny of calbindin immunoreactivity in the human hippocampal formation with a special emphasis on granule cells of the dentate gyrus.

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    Abrahám, Hajnalka; Veszprémi, Béla; Kravják, András; Kovács, Krisztina; Gömöri, Eva; Seress, László

    2009-04-01

    Calbindin (CB) is a calcium-binding protein that is present in principal cells as well as in interneurons of the hippocampal formation of various species including humans. Studies with transgenic mice revealed that CB is essential for long-term potentiation and synaptic plasticity which are the cellular basis of learning and memory. In a previous study we have shown that CB expression in granule cells of the dentate gyrus correlates with the functional maturation of the hippocampal formation in the rat. In the present study we examined the ontogeny of CB using immunohistochemistry in the human hippocampal formation paying special attention to the granule cells of the dentate gyrus. As early as the 14(th) week of gestation (GW), CB was being expressed by pyramidal cells of CA1-3 regions in the deepest cell rows of the pyramidal layer towards the ventricular zone. Later, CB sequentially appears in more superficial cell rows. After midgestation, CB disappears from CA3 pyramidal neurons. Expression of CB by granule cells starts at the 22(nd)-23(rd) GW, first by the most superficial neurons of the ectal end of the dorsal blade. At the 24(th) GW, CB is expressed by granule cells of the crest and medial portion of the ventral blade whereas later the entire ventral blade revealed CB immunoreactivity. At term, and in the first few postnatal months, CB-immunoreaction is detected in granule cells of both blades except for those neurons in the deepest cell rows at the hilar border. At around 2-3 years of age, all granule cells of the entire cell layer are CB-immunoreactive. Axons of granule cells, the mossy fibers, start to express CB around the 30(th) GW in stratum lucidum of CA3a. With further development, CB is expressed in CA3b and c, as well as in the hilus. An adult-like pattern of CB-immunoreactivity could be observed at 11 years of age. Our results indicate that (i) CB is expressed by hippocampal pyramidal cells a few weeks before midgestation; (ii) similarly to

  6. Locus Coeruleus Stimulation Facilitates Long-Term Depression in the Dentate Gyrus That Requires Activation of β-Adrenergic Receptors

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    Hansen, Niels; Manahan-Vaughan, Denise

    2015-01-01

    Synaptic plasticity comprises a cellular mechanism through which the hippocampus most likely enables memory formation. Neuromodulation, related to arousal, is a key aspect in information storage. The activation of locus coeruleus (LC) neurons by novel experience leads to noradrenaline release in the hippocampus at the level of the dentate gyrus (DG). We explored whether synaptic plasticity in the DG is influenced by activation of the LC via electrical stimulation. Coupling of test-pulses that evoked stable basal synaptic transmission in the DG with stimulation of the LC induced β-adrenoreceptor-dependent long-term depression (LTD) at perforant path–DG synapses in adult rats. Furthermore, persistent LTD (>24 h) induced by perforant path stimulation also required activation of β-adrenergic receptors: Whereas a β-adrenergic receptor antagonist (propranolol) prevented, an agonist (isoproterenol) strengthened the persistence of LTD for over 24 h. These findings support the hypothesis that persistent LTD in the DG is modulated by β-adrenergic receptors. Furthermore, LC activation potently facilitates DG LTD. This suggests in turn that synaptic plasticity in the DG is tightly regulated by activity in the noradrenergic system. This may reflect the role of the LC in selecting salient information for subsequent synaptic processing in the hippocampus. PMID:24464942

  7. Mechanism of Forelimb Motor Function Restoration after Cervical Spinal Cord Hemisection in Rats: A Comparison of Juveniles and Adults

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    Atsushi Hasegawa

    2016-01-01

    Full Text Available The aim of this study was to investigate forelimb motor function after cervical spinal cord injury in juvenile and adult rats. Both rats received a left segmental hemisection of the spinal cord after C3-C4 laminectomy. Behavioral evaluation of motor function was monitored and assessed using the New Rating Scale (NRS and Forelimb Locomotor Scale (FLS and by measuring the range of motion (ROM of both the elbow and wrist. Complete left forelimb motor paralysis was observed in both rats. The NRS showed motor function recovery restored to 50.2±24.7% in juvenile rats and 34.0±19.8% in adult rats. FLS was 60.4±26.8% in juvenile rats and 46.5±26.9% in adult rats. ROM of the elbow and wrist were 88.9±20.6% and 44.4±24.1% in juvenile rats and 70.0±29.2% and 40.0±21.1% in adult rats. Thus, the NRS and ROM of the elbow showed a significant difference between age groups. These results indicate that left hemisection of the cervical spinal cord was not related to right-sided motor functions. Moreover, while motor paralysis of the left forelimb gradually recovered in both groups, the improvement was greater in juvenile rats.

  8. Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats.

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    Piyanard Boonnate

    Full Text Available The amount of dietary monosodium glutamate (MSG is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology.Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group. All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets.MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated.Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account.

  9. Effect of morphine, naloxone and histamine system on water intake in adult male rats.

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    Eidi, Maryam; Oryan, Shahrbanoo; Eidi, Akram; Sepehrara, Leili

    2003-10-08

    The present study investigated the interaction between histamine and opioid systems on water intake in adult male rats. Intracerebroventricular (i.c.v.) injections were carried out in all experiments. Water intake was measured 1 h after drug injections. Administration of histamine (40-80 microg/rat) and naloxone (0.5-1 microg/rat) increased, while morphine (2.5 microg/rat), pyrilamine (25-50 microg/rat), the histamine H1 receptor antagonist, and ranitidine (10-20 microg/rat), the histamine H2 receptor antagonist, decreased water intake in isolated rats. Blockade of histamine H1 and H2 receptors attenuated the histamine-induced response. Pyrilamine, but not ranitidine, increased the inhibitory effect induced by morphine. Also, pharmacological blockade of histamine H1 and H2 receptors decreased the naloxone-induced effect on water intake. It is concluded that the histaminergic system may have a close interaction with morphine and naloxone on drinking behavior.

  10. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    Science.gov (United States)

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

  11. Effect of artemether on hematological parameters of healthy and uninfected adult Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Osonuga IO; Osonuga OA; Osonuga A; Onadeko AA; Osonuga AA

    2012-01-01

    Objective: To evaluate the effect of short term artemether administration on some blood parameters in adult male Wistar rats. Methods: Sixty five albino rats with body weight of 190-220 g were used for the four-phased study. The animals were randomly divided into five groups. The first-four groups of 15 rats were further divided into 3 subgroups of 5 rats. The drug was administered orally at sub-optimal, therapeutic, and high doses of 25, 50 and 75 mg/kg bw, respectively to the rats for 1 day, 2 days and 3 days. Blood samples were collected by cardio-puncture from the rats for hematology at the end of each phase. The last group served as control, and they were given water ad libitum. Results:Artemether caused significant reduction (P<0.05) of the hematological profile of the animals in a dose dependent manner. Discontinuation of the drug use however showed gradual recovery of the depressed indices of the blood parameters. Conclusions:The results suggest that artemether can induce reversible changes in hematological profiles of rats by extension man. This can probably aggravate anemia when artemether is administered to malaria patients. Hence, the study supports the use of the drug with caution especially in patients prone to anemic tendencies.

  12. Influence of endogenous ciliary neurotrophic factor on neural differentiation of adult rat hippocampal progenitors

    Institute of Scientific and Technical Information of China (English)

    Jun Ding; Zhili He; Juan Ruan; Ying Liu; Chengxin Gong; Shenggang Sun; Honghui Chen

    2013-01-01

    Ciliary neurotrophic factor is the only known neurotrophic factor that can promote differentiation of hippocampal neural progenitor cells to glial cells and neurons in adult rats. This process is similar to spontaneous differentiation. Therefore, ciliary neurotrophic factor may be involved in spontaneous differentiation of neural stem cells. To verify this hypothesis, the present study isolated neural progenitor cells from adult male rats and cultured them in vitro. Results showed that when neural progenitor cells were cultured in the absence of mitogen fibroblast growth factor-2 or epidermal growth factor, they underwent spontaneous differentiation into neurons and glial cells. Western blot and immunocytochemical staining showed that exogenous ciliary neurotrophic factor strongly induced adult hippocampal progenitor cells to differentiate into neurons and glial cells. Moreover, passage 4 adult hippocampal progenitor cells expressed high levels of endogenous ciliary neurotrophic factor, and a neutralizing antibody against ciliary neurotrophic factor prevented the spontaneous neuronal and glial differentiation of adult hippocampal progenitor cells. These results suggest that the spontaneous differentiation of adult hippocampal progenitor cells is mediated partially by endogenous ciliary neurotrophic factor.

  13. Potential testicular toxicity of sodium nitrate in adult rats.

    Science.gov (United States)

    Aly, Hamdy A A; Mansour, Ahmed M; Abo-Salem, Osama M; Abd-Ellah, Hala F; Abdel-Naim, Ashraf B

    2010-02-01

    Nitrate is a common contaminant in groundwater aquifers. Current study aimed at evaluating the potential testicular toxicity of sodium nitrate in rats. Sodium nitrate was given orally to rats at doses of 50, 100 or 200 mg/kg/day for 60 consecutive days. Sperm count and motility, daily sperm production and testis weight were significantly decreased specially at high doses. Testicular activity of lactate dehydrogenase-X, glucose-6-phosphate dehydrogenase, and acid phosphatase were inhibited in a dose-related manner. Lipid peroxides and hydrogen peroxide production were significantly increased in all treated animals. This was accompanied by inhibition of testicular activities of superoxide dismutase and glutathione peroxidase. Fifty mg/kg of sodium nitrate did not significantly alter catalase or glutathione reductase activity. Glutathione was significantly decreased by sodium nitrate in a dose-related manner. The decrease in sperm count and motility and daily sperm production was confirmed by histopathological studies which indicated chromatolysis, pyknosis and necrosis in spermatocytes. In conclusion, subchronic exposure of rats to sodium nitrate results in testicular toxicity as evidenced by decreased sperm count and motility, daily sperm production and testis weight, inhibited activity of enzyme markers of spermatogenesis and induction of histopathological changes. These effects are attributed, at least partly, to testicular oxidative stress.

  14. Repair of acutely injured spinal cord through constructing tissue-engineered neural complex in adult rats

    Institute of Scientific and Technical Information of China (English)

    PU Yu; GUO Qing-shan; WANG Ai-min; WU Si-yu; XING Shu-xing; ZHANG Zhong-rong

    2007-01-01

    Objective: To construct tissue-engineered neural complex in vitro and study its effect in repairing acutely injured spinal cord in adult rats. Methods: Neural stem cells were harvested from the spinal cord of embryo rats and propagated in vitro. Then the neural stem cells were seeded into polyglycolic acid scaffolds and co-cultured with extract of embryonic spinal cord in vitro. Immunofluorescence histochemistry and scanning electron microscope were used to observe the microstructure of this complex. Animal model of spine semi-transection was made and tissue-engineered neural complex was implanted by surgical intervention. Six weeks after transplantation, functional evaluation and histochemistry were applied to evaluate the functional recovery and anatomic reconstruction. Results: The tissue-engineered neural complex had a distinct structure, which contained neonatal neurons, oligodendrocytes and astrocytes. After tissue-engineered neural complex was implanted into the injured spinal cord, the cell components such as neurons, astrocytes and oligodendrocytes, could survive and keep on developing. The adult rats suffering from spinal cord injury got an obvious neurological recovery in motor skills. Conclusions: The tissue-engineered neural complex appears to have therapeutic effects on the functional recovery and anatomic reconstruction of the adult rats with spinal cord injury.

  15. Effects of Chronic 5-Bromo-2-Deoxyuridine Adminidtration on Spatial Memory in the Adult Rats

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    Mahmoud Hosseini

    2013-05-01

    Full Text Available Background: 5-Bromo-2-deoxyuridine (BrdU has been a principal marker for mitotic cells in studies of adult neurogenesis. The method consists of a pulse injection of BrdU into the intraperitoneal cavity followed by a variable survival time allowing for tracking the divided cells and their progeny. However, such exogenous markers may produce toxic effects. Aim of this study was determined the effects of Brdu on spatial memory in the adult rat. Materials and Methods: 16 Wistar rats were used in this experimental study. The rats were randomly divided into 2 groups (N=8 in each group, as follows: control and Brdu (50 mg/kg. Brdu was administered intraperitoneally for 6 weeks and then animals were used for behavioral testing in the Morris water maze. The data were analyzed with repeated measure’s ANOVA.Results: Our present findings show that there were no differences in the path length, escape latency and swim speed between control and Brdu-administrated groups.Conclusion: This study show that Brdu (exogenic proliferation marker did not has side effects on spatial memory in the adult rats.

  16. Cross-sensitization between testosterone and cocaine in adolescent and adult rats.

    Science.gov (United States)

    Engi, Sheila A; Cruz, Fabio C; Crestani, Carlos C; Planeta, Cleopatra S

    2015-11-01

    Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic-androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats.

  17. Effects of extremely low frequency magnetic field on anxiety level and spatial memory of adult rats

    Institute of Scientific and Technical Information of China (English)

    HE Li-hua; SHI Hong-mei; LIU Tong-tong; XUYing-chun; YE Kang-ping; WANG Sheng

    2011-01-01

    Background As the widespread use of electric devices in modern life,human are exposed to extremely low frequency magnetic fields (ELF MF) much more frequently than ever.Over the past decades,a substantial number of epidemiological and experimental studies have demonstrated that ELF MF (50 Hz) exposure is associated with increased risk of various health effects.The present study examined the effects of chronic exposure to ELF MF on anxiety level and spatial memory of adult rats.Methods The 50-Hz ELF MF was used during the whole experimental procedures and the value of magnetic field (MF)was set to 2 mT.Adult rats were divided randomly to control,MF 1 hour and MF 4 hours group.Anxiety-related behaviors were examined in the open field test and the elevated plus maze; changes in spatial learning and memory were determined in Morris water maze after 4 weeks of daily exposure.Results Rats in MF 4 hours group had increased anxiety-like behaviors with unaltered locomotor activity.In the Morris water maze test,rats had reduced latency to find the hidden platform and improved long-term memory of former location of platform without changes in short-term memory and locomotor activity.Conclusion Chronic ELF MF exposure has anxiogenic effect on rats,and the promoting effects on spatial learning and long-term retention of spatial memory.

  18. Enriched experience and recovery from amblyopia in adult rats: impact of motor, social and sensory components.

    Science.gov (United States)

    Baroncelli, Laura; Bonaccorsi, Joyce; Milanese, Marco; Bonifacino, Tiziana; Giribaldi, Francesco; Manno, Ilaria; Cenni, Maria Cristina; Berardi, Nicoletta; Bonanno, Giambattista; Maffei, Lamberto; Sale, Alessandro

    2012-06-01

    Amblyopia is one of the most common forms of visual impairment, arising from an early functional imbalance between the two eyes. It is currently accepted that, due to a lack of neural plasticity,amblyopia is an untreatable pathology in adults. Environmental enrichment (EE) emerged as a strategy highly effective in restoring plasticity in adult animals, eliciting recovery from amblyopia through a reduction of intracortical inhibition. It is unknown whether single EE components are able to promote plasticity in the adult brain, crucial information for designing new protocols of environmental stimulation suitable for amblyopic human subjects. Here, we assessed the effects of enhanced physical exercise,increased social interaction, visual enrichment or perceptual learning on visual function recovery in adult amblyopic rats. We report a complete rescue of both visual acuity and ocular dominance in exercised rats, in animals exposed to visual enrichment and in animals engaged in perceptual learning.These effects were accompanied by a reduced inhibition/excitation balance in the visual cortex. In contrast, we did not detect any sign of recovery in socially enriched rats or in animals practicing a purely associative visual task. These findings could have a bearing in orienting clinical research in the field of amblyopia therapy.

  19. Neonatal nociception elevated baseline blood pressure and attenuated cardiovascular responsiveness to noxious stress in adult rats.

    Science.gov (United States)

    Chu, Ya-Chun; Yang, Cheryl C H; Lin, Ho-Tien; Chen, Pin-Tarng; Chang, Kuang-Yi; Yang, Shun-Chin; Kuo, Terry B J

    2012-10-01

    Neonatal nociception has significant long-term effects on sensory perception in adult animals. Although neonatal adverse experience affect future responsiveness to stressors is documented, little is known about the involvement of early nociceptive experiences in the susceptibility to subsequent nociceptive stress exposure during adulthood. The aim of this study is to explore the developmental change in cardiovascular regulating activity in adult rats that had been subjected to neonatal nociceptive insults. To address this question, we treated neonatal rats with an intraplantar injection of saline (control) or carrageenan at postnatal day 1. The carrageenan-treated rats exhibited generalized hypoalgesia at basal state, and localized hyperalgesia after re-nociceptive challenge induced by intraplantar injections of complete Freund's adjuvant (CFA) as adults. Then we recorded baseline cardiovascular variables and 24-h responsiveness to an injection of CFA in the free-moving adult rats with telemetric technique. The carrageenan-treated rats showed significantly higher basal blood pressures (110.3±3.16 vs. control 97.0±4.28 mmHg). In control animals, baroreceptor reflex sensitivity (BRS) decreased, sympathetic vasomotor activity increased, and parasympathetic activity was inhibited after CFA injection. Blood pressure elevation was evident (107.0±2.75 vs. pre-injection 97.0±4.28 mmHg). Comparatively, the carrageenan-treated rats showed a higher BRS (BrrLF 1.03±0.09 vs. control 0.70±0.06 ms/mmHg) and higher parasympathetic activity [0.93±0.17 vs. control 0.32±0.02 ln(ms²)] after CFA injection. The change in blood pressure is negligible (111.9±4.05 vs. pre-injection 110.3±3.16 mmHg). Our research has shown that neonatal nociception alters future pain sensation, raises basal blood pressure level, and attenuates cardiovascular responsiveness to nociceptive stress in adult rats.

  20. Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats

    Directory of Open Access Journals (Sweden)

    Prince Gregory A

    2009-06-01

    Full Text Available Abstract Background Increased respiratory rate (tachypnea is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (Sigmodon hispidus also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection. Methods Lung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old and adult (6–12 week old cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph. Results Adult cotton rats had significantly greater tidal volume (TV, and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (Penh during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to Penh were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in Penh in infant animals. Conclusion While respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume is

  1. Induction of abnormal oocyte division under the constant light in the young adult rat

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Fangxiong Shi

    2012-01-01

    In order to study the effect of constant light on the ovary, 12 young adult female rats were exposed to constant light for 37 days and their estrous cycles were recorded by daily examination and the ovaries were examined histologically. The results showed that constant light induced in an abnormal and uncontrolled division of oocytes. In these divided-oocyte follicles (DOFs), two or more divided-oocytes shared one zona pellucida and usually floated freely in the follicular antrum. This fantastic phenomenon was discovered for the first time, and it was different from multioocyte follicles (MOFs) and polyovular follicles (POFs) founded in rats, humans, rabbits, mice and dogs.

  2. Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Teilum, Maria; Wieloch, Tadeusz

    2007-01-01

    including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated...... at 0-6 h of reperfusion for Neuritin and 0-12 h of reperfusion for Arc while BDNF was induced 0-9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part...

  3. Deletion of the Mouse Homolog of CACNA1C Disrupts Discrete Forms of Hippocampal-Dependent Memory and Neurogenesis within the Dentate Gyrus

    Science.gov (United States)

    Bell, Ryan Z.; Fisher, Grace L.

    2016-01-01

    Abstract L-type voltage-gated calcium channels (LVGCCs) have been implicated in various forms of learning, memory, and synaptic plasticity. Within the hippocampus, the LVGCC subtype, CaV1.2 is prominently expressed throughout the dentate gyrus. Despite the apparent high levels of CaV1.2 expression in the dentate gyrus, the role of CaV1.2 in hippocampal- and dentate gyrus-associated forms of learning remain unknown. To address this question, we examined alternate forms of hippocampal-dependent associative and spatial memory in mice lacking the mouse ortholog of CACNA1C (Cacna1c), which encodes CaV1.2, with dentate gyrus function implicated in difficult forms of each task. We found that while the deletion of CaV1.2 did not impair the acquisition of fear of a conditioned context, mice lacking CaV1.2 exhibited deficits in the ability to discriminate between two contexts, one in which the mice were conditioned and one in which they were not. Similarly, CaV1.2 knock-out mice exhibited normal acquisition and recall of the location of the hidden platform in a standard Morris water maze, but were unable to form a memory of the platform location when the task was made more difficult by restricting the number of available spatial cues. Within the dentate gyrus, pan-neuronal deletion of CaV1.2 resulted in decreased cell proliferation and the numbers of doublecortin-positive adult-born neurons, implicating CaV1.2 in adult neurogenesis. These results suggest that CaV1.2 is important for dentate gyrus-associated tasks and may mediate these forms of learning via a role in adult neurogenesis and cell proliferation within the dentate gyrus. PMID:27957527

  4. Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny.

    Science.gov (United States)

    Garoui, El Mouldi; Troudi, Afef; Fetoui, Hamadi; Soudani, Nejla; Boudawara, Tahia; Zeghal, Najiba

    2012-11-01

    The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl(2) in drinking water; group 3 received 350 ppm CoCl(2) in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity. Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.

  5. Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats.

    Science.gov (United States)

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-12-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes.

  6. Resveratrol improves reproductive parameters of adult rats varicocelized in peripuberty.

    Science.gov (United States)

    Mendes, Talita Biude; Paccola, Camila Cicconi; de Oliveira Neves, Flávia Macedo; Simas, Joana Noguères; da Costa Vaz, André; Cabral, Regina Elisabeth L; Vendramini, Vanessa; Miraglia, Sandra Maria

    2016-07-01

    The aim of this study was to investigate the protective action of resveratrol against the reproductive damage caused by left-sided experimental varicocele. There was a reduction of testicular major axis in the varicocele group when compared with the other groups; the testicular volume was reduced in varicocele group in comparison to the sham-control and resveratrol groups. The frequency of morphologically abnormal sperm was higher in varicocele and varicocele treated with resveratrol groups than in sham-control and resveratrol groups. The frequency of sperm with 100% of mitochondrial activity and normal acrosome integrity were lower in varicocele group than in varicocele treated with resveratrol, sham-control and resveratrol groups. Sperm motility was also reduced in varicocele group than in other groups. The sperm DNA fragmentation was higher in varicocele group than in other groups. Testicular levels of malondialdehyde were higher in varicocele and varicocele treated with resveratrol groups. The varicocele and varicocele treated with resveratrol groups had a significantly higher frequency of TUNEL-positive cells than sham-control and resveratrol groups; however, immunolabeling of the testes from varicocele treated with resveratrol group showed a lower number of apoptotic germ cells in comparison with the left testis of rats of the varicocele group. Reproductive alterations produced by varicocele from peripuberty were reduced by resveratrol in adulthood. Resveratrol should be better investigated as an adjuvant in the treatment of varicocele. Daily administration of resveratrol to rats with varicocele from peripuberty improves sperm quality in the adulthood.

  7. Electrophysiology of embryonic, adult and aged rat hippocampal neurons in serum-free culture.

    Science.gov (United States)

    Evans, M S; Collings, M A; Brewer, G J

    1998-01-31

    Methods were recently developed for culturing neurons from adult rat hippocampus using the serum-free medium Neurobasal with B27 supplement. To determine whether adult cultured neurons have normal electrical properties, we studied cultures from rats of three age groups: (1) embryonic; (2) 10-11 months old and (3) 35-36 months old. Neurons had a polarized morphology with a large branching apical dendrite and small basal dendrites. Mean resting potentials were similar in the three age groups. All neurons had nonlinear current-voltage relationships, indicating the presence of voltage-sensitive ion channels. Most neurons had a voltage-sensitive inward current followed by a sustained voltage-sensitive outward current. Tetrodotoxin blocked the inward current, which is likely to be a sodium current. The sustained outward current, which is likely to be a potassium current, reversed at -71 mV. Most neurons exhibited anomalous rectification. Calcium currents were present in both embryonic and adult neurons. Embryonic neurons would sometimes fire multiple action potentials but adult neurons fired only single action potentials. Our results indicate that both embryonic and adult cultured neurons retain a clearly neuronal electrophysiological phenotype in Neurobasal/B27 serum-free medium.

  8. Molecular and functional characterization of GAD67-expressing, newborn granule cells in mouse dentate gyrus

    Science.gov (United States)

    Cabezas, Carolina; Irinopoulou, Theano; Cauli, Bruno; Poncer, Jean Christophe

    2013-01-01

    Dentate gyrus granule cells (GCs) have been suggested to synthesize both GABA and glutamate immediately after birth and under pathological conditions in the adult. Expression of the GABA synthesizing enzyme GAD67 by GCs during the first few weeks of postnatal development may then allow for transient GABA synthesis and synaptic release from these cells. Here, using the GAD67-EGFP transgenic strain G42, we explored the phenotype of GAD67-expressing GCs in the mouse dentate gyrus. We report a transient, GAD67-driven EGFP expression in differentiating GCs throughout ontogenesis. EGFP expression correlates with the expression of GAD and molecular markers of GABA release and uptake in 2–4 weeks post-mitotic GCs. These rather immature cells are able to fire action potentials (APs) and are synaptically integrated in the hippocampal network. Yet they show physiological properties that differentiate them from mature GCs. Finally, GAD67-expressing GCs express a specific complement of GABAA receptor subunits as well as distinctive features of synaptic and tonic GABA signaling. Our results reveal that GAD67 expression in dentate gyrus GCs is a transient marker of late differentiation that persists throughout life and the G42 strain may be used to visualize newborn GCs at a specific, well-defined differentiation stage. PMID:23565079

  9. Effect of the antioxidant dibunol on adrenocortical, thyroid, and adenohypopyseal function in adult and old rats

    Energy Technology Data Exchange (ETDEWEB)

    Gorban' , E.N.

    1986-04-01

    This paper studies the effect of dibunol (4-methyl-2,6-di-tert-butylphenol) (D) on the function of the adrenal cortex, thyroid gland, and adenhypophysis, which produces trophic hormones for the other two glands. Experiments were carried out on adult rats. After injection of D concentrations of corticosterone (CS), triodothyronine (T/sub 3/), ACTH, and thyrotrophin (TSH) in the blood plasma and the CS concentration in tssue of the adenohypophysis were determined. It is shown that injection of D caused biphasic changes in the CS concentration in both tissues studied in adult and old animals.

  10. Temporal Expression of Mutant LRRK2 in Adult Rats Impairs Dopamine Reuptake

    Directory of Open Access Journals (Sweden)

    Hongxia Zhou, Cao Huang, Jianbin Tong, Weimin C Hong, Yong-Jian Liu, Xu-Gang Xia

    2011-01-01

    Full Text Available Parkinson's disease (PD results from progressive degeneration of dopaminergic neurons. Most PD cases are sporadic, but some have pathogenic mutation in the individual genes. Mutation of the leucine-rich repeat kinase-2 (LRRK2 gene is associated with familial and sporadic PD, as exemplified by G2019S substitution. While constitutive expression of mutant LRRK2 in transgenic mice fails to induce neuron death, transient expression of the disease gene by viral delivery causes a substantial loss of dopaminergic neurons in mice. To further assess LRRK2 pathogenesis, we created inducible transgenic rats expressing human LRRK2 with G2019S substitution. Temporal overexpression of LRRK2G2019S in adult rats impaired dopamine reuptake by dopamine transporter (DAT and thus enhanced locomotor activity, the phenotypes that were not observed in transgenic rats constitutively expressing the gene throughout life time. Reduced DAT binding activity is an early sign of dopaminergic dysfunction in asymptomatic subjects carrying pathogenic mutation in LRRK2. Our transgenic rats recapitulated the initiation process of dopaminergic dysfunction caused by pathogenic mutation in LRRK2. Inducible transgenic approach uncovered phenotypes that may be obscured by developmental compensation in constitutive transgenic rats. Finding in inducible LRRK2 transgenic rats would guide developing effective strategy in transgenic studies: Inducible expression of transgene may induce greater phenotypes than constitutive gene expression, particularly in rodents with short life time.

  11. Effects of cyclophosphamide on the kaolin consumption (pica behavior) in five strains of adult male rats.

    Science.gov (United States)

    Tohei, Atsushi; Kojima, Shu-ichi; Ikeda, Masashi; Hokao, Ryoji; Shinoda, Motoo

    2011-07-01

    It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.

  12. Impairment in Spatial Memory in adult Rats following developmental Low Lead Exposure

    Directory of Open Access Journals (Sweden)

    Rajashekar Rao Barkur

    2012-11-01

    Full Text Available The present study was aimed to investigate the effect of environmentally relevant levels of lead exposure during gestational and early postnatal period on hippocampal dependent spatial memory in rats during adulthood. The pregnant rats were allowed to drink either normal water (control group or 0.2% lead acetate solution (Leadtreated group during pregnancy and lactation. Thus rats pups of lead treated group where exposed to lead indirectly through their mothers during this period. At weaning pups of lead treated group were allowed to drink normal water till they attain the adult hood. Blood lead level was estimated on postnatal day 22 and 120. Birth weight and weight gain of the rat pups as they grew were measured at regular intervals. Both the control and lead treated groups of rats were subjected to water maze test on postnatal day 30 and 120. Results showed that lead treatment had no effect on birth weight or weight gain. Blood lead level on postnatal day 22 was significantly high in treated group compared to the control group and it was normalized by end of four months. The rats born to lead treated mothers showed impaired in spatial memory during water maze test both on postnatal day 36 and 126. These data suggests that exposure to environmentally relevant levels of lead during intrauterine and early postnatal period of brain development causes impairment in spatial memory not only during infancy but also lasts till adulthood.

  13. Adolescent social defeat disturbs adult aggression-related impulsivity in wild-type rats.

    Science.gov (United States)

    Coppens, Caroline M; Coolen, Alex; de Boer, Sietse F; Koolhaas, Jaap M

    2014-10-01

    Adolescence is generally considered as a developmental period during which adverse social experiences may have lasting consequences in terms of an increased vulnerability to affective disorders. This study aimed at determining the individual susceptibility to adolescent social stress using a rat model. We used rats of the Wild-type Groningen strain, which are characterized by a broad variation in adult levels of aggression and impulsivity. We hypothesized that experience of social defeat in adolescence results in heightened aggression and impulsivity levels in adulthood. In contrast to our expectation, adolescent social defeat did not lead to a difference in the average adult level of aggression and impulsivity, but the significant correlation between offensive aggression and impulsivity found in control animals was not present in animals defeated during adolescence.

  14. Retrograde Labeling of Adult Rat Retinal Ganglion Cells with the Flurogold

    Institute of Scientific and Technical Information of China (English)

    Wei Huang; Yannian Hui; Miaoli Zhang

    2000-01-01

    Purpose: To study the densities and distribution of retinal ganglion cells(RGC) in adult rat retinae with flurogold(FG) labeling retogradely.Methods: FG was injected to the superior colliculi(SC) and dorsal lateral geniculate nuclei (dLGN) in adult rats and the retinae were examined by fluorescence microscopy at various periods of time.Results: FG-labelled RGC were observed in the retina as early as 3 days after application of FG. The labelled cells gradually increased in density, reached 95% of the maximal number on days 7 and the maximal number on days 30. The density of labelled cells was higher in the posterior pole than in the peripheral area. The fluorescence intensity in labelled cells maintained up to 60 days.Conclusion: The FG retrograde labeling method is reliable and effective for quantity of RGC. Eye Science 2000; 16:29 ~ 33.

  15. Retrograde Labeling of Adult Rat Retinal Ganglion Cells with the Flurogold

    Institute of Scientific and Technical Information of China (English)

    WeiHuang; YannianHui; 等

    2002-01-01

    Purpose:To study the densities and distribution of retinal ganglion cells(RGC) in adult rat retinae with flurogold(FG) labeling retogradely.Methods:FG was injected to the superior colliculid(SC) and dorsal lateral geniculate nuclei(dLGN) in adult rats and the retinae were examined by fluorescence microscopy at various periods of time.Results:FG-labelled RGC were observed in the retina as early as 3 days after application of FG.The labeled cells gradually increased in density,reached 95% of the maximal number on days 7 and the maximal nuber on days 30.The density of labeled cells was higher in the posterior pole than in the peripheral area.The fluorescence intensity in labeled cells maintained up to 60 days.Conclusion:The FG retrograde labeling method is reliable and effective for quantity of RGC.Eye Science 2000;46:29-33.

  16. Immunohistochemical localization of glutamate transporter EAAC1 in the brainstem of adult rat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Fu-xing; LIU Tao; ZHAO Jing-wei; LI Jin-lian; DONG Yu-lin; LI Ji-shuo

    2001-01-01

    Objective: To observe the distribution of EAAC1, a subtype of glutamate transporters, in the brainstem of adult rat. Methods: Immunocytochemical staining with avidin-biotin complex (ABC) method was employed. Results:EAAC1 was widely distributed throughout the brainstem. In many regions, the EAAC1-like immunoreactivity was primarily distributed in the neuropil. Cell body staining was observed in the prepositus hypoglossal nucleus, external cortex of the inferior colliculus, red nucleus, substantia nigra, mesencephalic raphe nuclei, ventral tegmental nucleus, superior olivary complex, nucleus of the trapezoid body, cochlear nucleus, sensory trigeminal complex, Barrington's nucleus,trigeminal motor nucleus, parabrachial nuclei, dorsal nucleus of vagus, hypoglossal nucleus, locus coeruleus, lateral and superior vestibular nuclei, lateral paragigantocellular nucleus and dorsal paragigantocellular nucleus. Conclusion: Glutamate transporter EAAC 1 is widely distributed throughout the brainstem of adult rat, which may play an important role in excitatory activities of the neurons induced by glutamate.

  17. Organotypic explant culture of adult rat retina for in vitro investigations of neurodegeneration, neuroprotection and cell transplantation

    OpenAIRE

    sprotocols

    2015-01-01

    This protocol details a method for isolating retinal tissue from adult rats as an organotypic culture to study neurobiological processes in mature tissue. It combines the efficiency and control common to in vitro techniques with close imitation of the in vivo environment. Eyes from adult rats are enucleated and the neural retina is isolated. Tissue is cut into quarters, yielding eight retinal explants per animal, and cultured at a fluid/air interface on organotypic culture membranes. Explanta...

  18. Toxicity Induced after Subchronic Administration of the Synthetic Food Dye Tartrazine in Adult Rats, Role of Oxidative Stress

    OpenAIRE

    Narges El Golli; Ines Bini-Dhouib; Aicha Jrad; Imene Boudali; Basma Nasri; Nadia Belhadjhmida; Saloua El Fazaa

    2016-01-01

    The present study was conducted to evaluate the toxic potential of tartrazine, a food color, in different tissues in adult rat: blood, liver, kidneys, and spleen. Tartrazine was administered orally at a dose of 300 mg/kg of body weight to adult male Wistar rats during a period of 30 days. Tartrazine treatment led to an increase in platelets count, a reduction in peripheral lymphocytes and in spleen T CD8-lymphocytes. Furthermore, tartrazine increased the activities of hepatocellular enzymes a...

  19. Differentiation of endogenous neural precursors following spinal cord injury in adult rats

    Institute of Scientific and Technical Information of China (English)

    Bin Zhao; Hua Han; Shuanke Wang; Bingren Gao; Zhengyi Sun

    2008-01-01

    BACKGROUND:Studies have shown that cell death can activate proliferation of endogenous neural stem cells and promote newly generated cells to migrate to a lesion site.OBJECTIVE:To observe regeneration and differentiation of neural cells following spinal cord injury in adult rats and to quantitatively analyze the newly differentiated cells.DESIGN,TIME AND SETTING:A cell biology experiment was performed at the Institute of Orthopedics and Medical Experimental Center,Lanzhou University.between August 2005 and October 2007.MATERIALS:Fifty adult,Wistar rats of both sexes;5-bromodeoxyuridine(BrdU,Sigma,USA);antibodies against neuron-specific enolase,glial fibrillary acidic protein,and myelin basic protein(Chemicon,USA).METHODS:Twenty-five rats were assigned to the spinal cord injury group and received a spinal cord contusion injury.Materials were obtained at day 1,3,7,15,and 29 after injury,with 5 rats for each time point.Twenty-five rats were sham-treated by removing the lamina of the vertebral arch without performing a contusion.MAIN OUTCOME MEASURES:The phenotype of BrdU-labeled cells,i.e.,expression and distribution of surface markers for neurons(neuron-specific enolase),astrocytes(glial fibrillary acidic protein),and oligodendrocytes(myelin basic protein),were identified with immunofluorescence double-labeling.Confocal microscopy was used to detect double-labeled cells by immunofluorescence.Quantitative analysis of newly generated cells was performed with stereological counting methods.RESULTS:There was significant cell production and differentiation after adult rat spinal cord injury.The quantity of newly-generated BrdU-labeled cells in the spinal cord lesion was 75-fold greater than in the corresponding area of control animals.Endogenous neural precursor cells differentiated into astrocytes and oligodendrocytes,however spontaneous neuronal difierentiation was not detected.Between 7 and 29 d after spinal cord injury,newly generated cells expressed increasingly more

  20. Role of the dentate gyrus in mediating object-spatial configuration recognition.

    Science.gov (United States)

    Kesner, Raymond P; Taylor, James O; Hoge, Jennifer; Andy, Ford

    2015-02-01

    In the present study the effects of dorsal dentate gyrus (dDG) lesions in rats were tested on recognition memory tasks based on the interaction between objects, features of objects, and spatial features. The results indicated that the rats with dDG lesions did not differ from controls in recognition for a change within object feature configuration and object recognition tasks. In contrast, there was a deficit for the dDG lesioned rats relative to controls in recognition for a change within object-spatial feature configuration, complex object-place feature configuration and spatial recognition tasks. It is suggested that the dDG subregion of the hippocampus supports object-place and complex object-place feature information via a conjunctive encoding process.

  1. Adult neurogenesis: integrating theories and separating functions

    OpenAIRE

    2010-01-01

    The continuous incorporation of new neurons in the dentate gyrus of the adult hippocampus raises exciting questions about memory and learning, and has inspired new computational models to understand the function of adult neurogenesis. These theoretical approaches suggest distinct roles for new neurons as they slowly integrate into the existing dentate gyrus network: immature adult-born neurons appear to function as pattern integrators of temporally adjacent events, thereby enhancing pattern s...

  2. Neural stem cell- and neurogenesis-related gene expression profiles in the young and aged dentate gyrus

    OpenAIRE

    Shetty, Geetha A.; Hattiangady, Bharathi; Shetty, Ashok K.

    2013-01-01

    Hippocampal neurogenesis, important for memory and mood function, wanes greatly in old age. Studies in rat models have implied that this decrease is not due to loss of neural stem cells (NSCs) in the subgranular zone of the dentate gyrus (DG) but rather due to an increased quiescence of NSCs. Additional studies have suggested that changes in the microenvironment, particularly declines in the concentrations of neurotrophic factors, underlie this change. In this study, we compared the expressio...

  3. Neurones in the adult rat anterior medullary velum.

    Science.gov (United States)

    Ibrahim, M; Menoud, P A; Celio, M R

    2000-03-27

    The presence of neurones in the rat anterior medullary velum (AMV) has been investigated by using antibodies to the calcium-binding proteins, parvalbumin (PV), calretinin (CR), and calbindin-D28k (CB). Disparate populations of mainly GABAergic neurones were located in the rostral and caudal regions of the AMV. The rostral region of the AMV was characterised by GABAergic CR-labelled or PV-labelled neurones. CR-labelled neurones were bipolar or multipolar with round to ovoid somata (diameters between 8 and 12 microm), and rostrocaudally running dendrites forming a network. PV-labelled neurones had round somata (diameters between 6 and 10 microm) and were bi-tufted, with beaded dendrites. Both CR-labelled and PV-labelled dendrites formed punctate pericellular associations with unlabelled somatic profiles. In the caudal region of the AMV, PV-labelled neurones were GABAergic, multipolar cells, having round somata (diameters between 9 and 12 microm), with either beaded or nonbeaded dendrites forming a network of interconnecting dendrites. PV-labelled pericellular associations were made around both PV-labelled and unlabelled somatic profiles. CR labelled unipolar brush cells (UBCs) were not GABAergic. UBCs were characterised by a round to oval somata (10-15 microm in diameter) from which a single primary dendrite emerged to form a distal expansion having small terminal dendrites. From the distal expansion, there also appeared to be CR-labelled processes emanating and extending for up to 250 microm. CB occasionally labelled "Purkinje-like cells" (PLCs). The rat AMV is a more complex structure than first envisaged with the presence of predominantly inhibitory neurones expressing different calcium-binding proteins. Functional and anatomic aspects of this circuitry are further discussed.

  4. Effect of Camphor on Pituitary-Gonadal Hormonal Axis and Oogenesis in Adult Female Rats

    OpenAIRE

    Habibollah Johari; Amir Ashkan Mahjoor; Siyamak Fallahi; Hossein Kargar Jahromi; Maryam Abedini; Mohammad Ali Poor Danesh; Zahra Zamani

    2013-01-01

    Background & Objective: Camphor stimulates the nervous system and the circulatory system, reduces lactation, and prevents conception and embryo embedding. We investigated the effects of camphor on the pituitary-gonadal hormonal axis and concentration of steroidal hormones.   Materials & Methods: The parameters investigated were concentrations of LH, FSH, estrogen, progesterone, and testosterone. Forty adult female rats at a mean weight of 180 ± 20 grams were divided into five groups. Camphor ...

  5. Selection of medium for serum-free primary culture of adult rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Miyazaki,Masahiro

    1990-02-01

    Full Text Available To select a suitable medium for serum-free primary culture of adult rat hepatocytes, ten commercially-available synthetic media were compared for their ability to maintain the cells under serum-free and serum-supplemented conditions with special reference to attachment, survival and albumin secretion. It was found that Williams' medium E and DM-160 medium were the best among the ten media for maintaining hepatocytes under serum-free conditions in primary culture.

  6. Use of the light/dark test for anxiety in adult and adolescent male rats.

    Science.gov (United States)

    Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M

    2013-11-01

    The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α₂ adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence.

  7. Methylmercury chloride damage to the adult rat hippocampus cannot be detected by proton magnetic resonance spectroscopy

    Institute of Scientific and Technical Information of China (English)

    Zhiyan Lu; Jinwei Wu; Guangyuan Cheng; Jianying Tian; Zeqing Lu; Yongyi Bi

    2014-01-01

    Previous studies have found that methylmercury can damage hippocampal neurons and accord-ingly cause cognitive dysfunction. However, a non-invasive, safe and accurate detection method for detecting hippocampal injury has yet to be developed. This study aimed to detect methylmer-cury-induced damage on hippocampal tissue using proton magnetic resonance spectroscopy. Rats were given a subcutaneous injection of 4 and 2 mg/kg methylmercury into the neck for 50 consecutive days. Water maze and pathology tests confirmed that cognitive function had been impaired and that the ultrastructure of hippocampal tissue was altered after injection. The results of proton magnetic resonance spectroscopy revealed that the nitrogen-acetyl aspartate/creatine, choline complex/creatine and myoinositol/creatine ratio in rat hippocampal tissue were unchanged. Therefore, proton magnetic resonance spectroscopy can not be used to determine structural damage in the adult rat hippocampus caused by methylmercury chloride.

  8. Localization of Sonic hedgehog secreting and receiving cells in the developing and adult rat adrenal cortex.

    Science.gov (United States)

    Guasti, Leonardo; Paul, Alex; Laufer, Ed; King, Peter

    2011-04-10

    Sonic hedgehog signaling was recently demonstrated to play an important role in murine adrenal cortex development. The organization of the rat adrenal differs from that of the mouse, with the zona glomerulosa and zona fasciculata separated by an undifferentiated zone in the rat, but not in the mouse. In the present study we aimed to determine the mRNA expression patterns of Sonic hedgehog and the hedgehog signaling pathway components Patched-1 and Gli1 in the developing and adult rat adrenal. Sonic hedgehog expression was detected at the periphery of the cortex in cells lacking CYP11B1 and CYP11B2 expression, while signal-receiving cells were localized in the overlying capsule mesenchyme. Using combined in situ hybridization and immunohistochemistry we found that the cells expressing Sonic hedgehog lie between the CYP11B2 and CYP11B1 layers, and thus Sonic hedgehog expression defines one cell population of the undifferentiated zone.

  9. Qualitative and quantitative analysis of bones in adult rats by repeated intraperitoneal administration of paclitaxel (taxol) using radioisotope EDXRF technique

    Energy Technology Data Exchange (ETDEWEB)

    Oezdemir, Y. E-mail: yozdemir25@yahoo.com; Iyiguen, Ibrahim; Durak, Ridvan

    2003-05-15

    Energy dispersive X-ray fluorescence analysis of right back leg bone samples taken from adult female rats administered paclitaxel (taxol) was carried out using standard addition method. Because qualitative and quantitative data analysis of rat bone samples is not found in the literature, comparison was not made with other experimental results. Our experimental results are presented and discussed in this study.

  10. Methods to evaluate functional nerve recovery in adult rats : walking track analysis, video analysis and the withdrawal reflex

    NARCIS (Netherlands)

    Dijkstra, [No Value; Meek, MF; Robinson, PH; Gramsbergen, A

    2000-01-01

    The aim of this study was to compare different methods for the evaluation of functional nerve recovery. Three groups of adult male Wistar rats were studied. In group A, a 12-mm gap between nerve ends was bridged by an autologous nerve graft; in rats of group B we performed a crush lesion of the scia

  11. A method for unit recording in the lumbar spinal cord during locomotion of the conscious adult rat

    DEFF Research Database (Denmark)

    Berg, Rune W; Chen, Ming-Teh; Huang, Hsueh-Chen;

    2009-01-01

    Extracellular recordings from single units in the brain, for example the neocortex, have proven feasible in moving, awake rats, but have not yet been possible in the spinal cord. Single-unit activity during locomotor-like activity in reduced preparations from adult cats and rats have provided...

  12. Behavioral Differences Between Late Preweanling and Adult Female Sprague-Dawley Rat Exploration of Animate and Inanimate Stimuli and Food

    OpenAIRE

    Smith, Kiersten S.; Morrell, Joan I.

    2010-01-01

    The late preweanling rat has potential as a preclinical model for disorders initially manifested in early childhood that are characterized by dysfunctional interactions with specific stimuli (e.g., obsessive-compulsive disorder and autism). No reports, however, of specific-stimulus exploration in the late preweanling rat are found in the literature. We examined the behavioral responses of normal late preweanling (PND 18-19) and adult rats when presented with exemplars of categorically-varied ...

  13. Cardiac and plasma lipid profiles in response to acute hypoxia in neonatal and young adult rats

    Directory of Open Access Journals (Sweden)

    Raff Hershel

    2010-01-01

    Full Text Available Abstract Background The physiological and biochemical responses to acute hypoxia have not been fully characterized in neonates. Fatty acids and lipids play an important role in most aspects of cardiac function. Methods We performed comprehensive lipid profiling analysis to survey the changes that occur in heart tissue and plasma of neonatal and young adult rats exposed to hypoxia for 2 h, and following 2 h of recovery from hypoxia. Results Cardiac and plasma concentrations of short-chain acylcarnitines, and most plasma long-chain fatty acids, were decreased in hypoxic neonates. Following recovery from hypoxia, concentrations of propionylcarnitine, palmitoylcarnitine, stearoylcarnitine were increased in neonatal hearts, while oleylcarnitine and linoleylcarnitine concentrations were increased in neonatal plasma. The concentrations of long-chain fatty acids and long-chain acylcarnitines were increased in the hearts and plasma of hypoxic young adult rats; these metabolites returned to baseline values following recovery from hypoxia. Conclusion There are differential effects of acute hypoxia on cardiac and plasma lipid profiles with maturation from the neonate to the young adult rat. Changes to neonatal cardiac and plasma lipid profiles during hypoxia likely allowed for greater metabolic and physiologic flexibility and increased chances for survival. Persistent alterations in the neonatal cardiac lipid profile following recovery from hypoxia may play a role in the development of rhythm disturbances.

  14. Effects of estradiol and methoxychlor on Leydig cell regeneration in the adult rat testis.

    Science.gov (United States)

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-05-06

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7-15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

  15. Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

    Directory of Open Access Journals (Sweden)

    Bingbing Chen

    2014-05-01

    Full Text Available The objective of the present study is to determine whether methoxychlor (MXC exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2. Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control, 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

  16. Imipramine reverses alterations in cytokines and BDNF levels induced by maternal deprivation in adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Ribeiro, Karine F; Petronilho, Fabrícia; Vuolo, Francieli; Colpo, Gabriela D; Pfaffenseller, Bianca; Kapczinski, Flávio; Dal-Pizzol, Felipe; Quevedo, João

    2013-04-01

    A growing body of evidence is pointing toward an association between immune molecules, as well brain-derived neurotrophic factor (BDNF) and the depression. The present study was aimed to evaluate the behavioral and molecular effects of the antidepressant imipramine in maternally deprived adult rats. To this aim, maternally deprived and non-deprived (control group) male rats were treated with imipramine (30mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming test. In addition to this, IL-10, TNF-α and IL-1β cytokines were assessed in the serum and cerebrospinal fluid (CSF). In addition, BDNF protein levels were assessed in the prefrontal cortex, hippocampus and amygdala. In deprived rats treated with saline was observed an increase on immobility time, compared with non-deprived rats treated with imipramine (pimipramine treatment reversed the effects of maternal deprivation on BDNF and cytokines levels (pimipramine, it is suggested that classic antidepressants could exert their effects by modulating the immune system.

  17. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    Science.gov (United States)

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

  18. Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

    Science.gov (United States)

    Soliz, Jorge; Tam, Rose; Kinkead, Richard

    2016-01-01

    Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders. PMID:27729873

  19. Basic fibroblast growth factor protects against excitotoxicity and chemical hypoxia in both neonatal and adult rats.

    Science.gov (United States)

    Kirschner, P B; Henshaw, R; Weise, J; Trubetskoy, V; Finklestein, S; Schulz, J B; Beal, M F

    1995-07-01

    Basic fibroblast growth factor (bFGF) is a polypeptide growth factor that promotes neuronal survival. We recently found that systemic administration of bFGF protects against both excitotoxicity and hypoxia-ischemia in neonatal animals. In the present study, we examined whether systemically administered bFGF could prevent neuronal death induced by intrastriatal injection of N-methyl-D-aspartate (NMDA) or chemical hypoxia induced by intrastriatal injection of malonate in adult rats and 1-methyl-4-phenylpyridinium (MPP+) in neonatal rats. Systemic administration of bFGF (100 micrograms/kg) for three doses both before and after intrastriatal injection of either NMDA or malonate in adult rats produced a significant neuroprotective effect. In neonatal rats, bFGF produced dose-dependent significant neuroprotective effects against MPP+ neurotoxicity, with a maximal protection of approximately 50% seen with either a single dose of bFGF of 300 micrograms/kg or three doses of 100 micrograms/kg. These results show that systemic administration of bFGF is effective in preventing neuronal injury under circumstances in which the blood-brain barrier may be compromised, raising the possibility that this strategy could be effective in stroke.

  20. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-01-01

    Full Text Available Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24, with average weight of 220g were randomly assigned into two treatments (A & B of (n=16 and Control (c (n=8 groups. The rats in the treatment groups (A & B received 0.1g (500mg/kg body weight and 0.2g (1000mg/kg body weight of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c received equal amount of feeds daily without nutmeg added for forty-two days. The growers′ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings.

  1. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-04-01

    Full Text Available Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24, with average weight of 220g were randomly assigned into two treatments (A & B of (n=16 and Control (c (n=8 groups. The rats in the treatment groups (A & B received 0.1g (500mg/kg body weight and 0.2g (1000mg/kg body weight of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c received equal amount of feeds daily without nutmeg added for forty-two days. The growers’ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings.

  2. Hippocampal interneurons expressing glutamic acid decarboxylase and calcium-binding proteins decrease with aging in Fischer 344 rats.

    Science.gov (United States)

    Shetty, A K; Turner, D A

    1998-05-04

    Aging leads to alterations in the function and plasticity of hippocampal circuitry in addition to behavioral changes. To identify critical alterations in the substrate for inhibitory circuitry as a function of aging, we evaluated the numbers of hippocampal interneurons that were positive for glutamic acid decarboxylase and those that expressed calcium-binding proteins (parvalbumin, calbindin, and calretinin) in young adult (4-5 months old) and aged (23-25 months old) male Fischer 344 rats. Both the overall interneuron population and specific subpopulations of interneurons demonstrated a commensurate decline in numbers throughout the hippocampus with aging. Interneurons positive for glutamic acid decarboxylase were significantly depleted in the stratum radiatum of CA1, the strata oriens, radiatum and pyramidale of CA3, the dentate molecular layer, and the dentate hilus. Parvalbumin interneurons showed significant reductions in the strata oriens and pyramidale of CA1, the stratum pyramidale of CA3, and the dentate hilus. The reductions in calbindin interneurons were more pronounced than other calcium-binding protein-positive interneurons and were highly significant in the strata oriens and radiatum of both CA1 and CA3 subfields and in the dentate hilus. Calretinin interneurons were decreased significantly in the strata oriens and radiatum of CA3, in the dentate granule cell and molecular layers, and in the dentate hilus. However, the relative ratio of parvalbumin-, calbindin-, and calretinin-positive interneurons compared with glutamic acid decarboxylase-positive interneurons remained constant with aging, suggesting actual loss of interneurons expressing calcium-binding proteins with age. This loss contrasts with the reported preservation of pyramidal neurons with aging in the hippocampus. Functional decreases in inhibitory drive throughout the hippocampus may occur due to this loss, particularly alterations in the processing of feed-forward information through the

  3. BTG1 is required to maintain the pool of stem and progenitor cells of dentate gyrus and subventricular zone

    Directory of Open Access Journals (Sweden)

    Stefano eFarioli-Vecchioli

    2012-08-01

    Full Text Available Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ. Thus, we generated Btg1 knockout mice to analyze the role of Btg1 in the process of generation of adult new neurons.Ablation of Btg1 causes a transient increase of the proliferating dentate gyrus stem and progenitor cells at post-natal day 7; however, at two months of age the number of these proliferating cells, as well as of mature neurons, greatly decreases compared to wild-type controls. Remarkably, adult dentate gyrus stem and progenitor cells of Btg1-null mice exit cell cycle after completing the S phase, highly express p53 and p21, and within 5 days undergo apoptosis. In SVZ we observed an equivalent decrease, associated to apoptosis, of Btg1-null stem cells, neuroblasts and neurons; furthermore, neurospheres derived from SVZ stem cells showed an age-dependent decrease of the self-renewal and expansion capacity.We conclude that the ablation of Btg1 reduces the pool of dividing adult stem and progenitor cells in dentate gyrus and SVZ by decreasing their proliferative capacity and inducing apoptosis, likely reflecting the impairment of the control of the cell cycle transition from G1 to S phase. As a result, the ability of Btg1-null mice to discriminate among overlapping contextual memories was affected. Thus, Btg1 appears to be required for maintaining adult stem and progenitor cells quiescence and self-renewal.

  4. Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats.

    Science.gov (United States)

    Montandon, Gaspard; Horner, Richard L; Kinkead, Richard; Bairam, Aida

    2009-11-15

    Caffeine is commonly used clinically to treat apnoeas and unstable breathing associated with premature birth. Caffeine antagonizes adenosine receptors and acts as an efficient respiratory stimulant in neonates. Owing to its persistent effects on adenosine receptor expression in the brain, neonatal caffeine administration also has significant effects on maturation of the respiratory control system. However, since adenosine receptors are critically involved in sleep regulation, and sleep also modulates breathing, we tested the hypothesis that neonatal caffeine treatment disrupts regulation of sleep and breathing in the adult rat. Neonatal caffeine treatment (15 mg kg(-1) day(-1)) was administered from postnatal days 3-12. At adulthood (8-10 weeks old), sleep and breathing were measured with a telemetry system and whole-body plethysmography respectively. In adult rats treated with caffeine during the neonatal period, sleep time was reduced, sleep onset latency was increased, and non-rapid eye movement (non-REM) sleep was fragmented compared to controls. Ventilation at rest was higher in caffeine-treated adult rats compared to controls across sleep/wake states. Hypercapnic ventilatory responses were significantly reduced in caffeine-treated rats compared to control rats across sleep/wake states. Additional experiments in adult anaesthetized rats showed that at similar levels of arterial blood gases, phrenic nerve activity was enhanced in caffeine-treated rats. This study demonstrates that administration of caffeine in the neonatal period alters respiratory control system activity in awake and sleeping rats, as well as in the anaesthetized rats, and also has persistent disrupting effects on sleep that are apparent in adult rats.

  5. Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

    Science.gov (United States)

    Greco, Tiffany; Hovda, David A; Prins, Mayumi L

    2015-02-01

    Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults.

  6. Strong evidence for pattern separation in human dentate gyrus

    NARCIS (Netherlands)

    Berron, David; Schütze, Hartmut; Maass, Anne; Cardenas-Blanco, Arturo; Kuijf, Hugo J.; Kumaran, Dharshan; Düzel, Emrah

    2016-01-01

    The hippocampus is proposed to be critical in distinguishing between similar experiences by performing pattern separation computations that create orthogonalized representations for related episodes. Previous neuroimaging studies have provided indirect evidence that the dentate gyrus (DG) and CA3 hi

  7. The time course of denervation-induced changes is similar in soleus muscles of adult and old rats.

    NARCIS (Netherlands)

    Degens, H.; Kosar, S.N.; Hopman, M.T.E.; Haan, A. de

    2008-01-01

    Muscle denervation is accompanied by atrophy and a decline in oxidative capacity. We investigated whether the time course of adaptations following denervation of the soleus muscle differs in adult (5 months old) and older adult (25 months old) rats. We denervated the soleus muscle of the left leg, w

  8. A SELF-PRIMING EFFECT OF LHRH ON LH SECRETION IN DISPERSED ANTERIOR PITUITARY CELLS OF ADULT MALE RAT

    Institute of Scientific and Technical Information of China (English)

    QUZhi-Chao; GUOJing; GUOJian

    1989-01-01

    LHRH self-priming effect is simply defmed as an enhancement of LH response to LHRH, i. e., a second challenge with LHRH elicits more LH secretion as compared to the first challenge. The present study is to observe whether this phenomenon exists in perfused anterior pituitary (AP) cells of adult male rat. Dispersed AP cells of adult SD

  9. ZP2307, a novel cyclic PTH(1-17) analog, reversed established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Vääräniemi, Jukka; Morko, Jukka; Peng, ZhiQi

    -17) analog, ZP2307, with a high efficacy and potency on the human PTH receptor in vitro. This study characterized the effects of intermittent treatment with ZP2307 on established osteopenia in adult ovariectomized (OVX) rats. Female Sprague-Dawley rats were ovariectomized at 6 months of age. After 6 weeks......-34). This study demonstrated that the intermittent treatment with ZP2307, the novel cyclic PTH(1-17) analog, is effective in reversing the established osteopenia in adult OVX rats to normal conditions. Due to its broad dose response relationship, ZP2307 may have a wider therapeutic window and a better safety...

  10. Effect of glial cell line-derived neurotrophic factor on peripheral nerve regeneration in adult rat

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe-yu; LI Jian-hong; ZHENG Xing-dong; LU Chang-lin; HE Cheng

    2001-01-01

    Objective: To study the effect of glial cell line-derived neurotrophic (GDNF) on adult peripheral nerve regeneration. Methods: Transectioned sciatic nerve in adult rats was sutured into silicone channel. GDNF or SAL solution was injected into the silicone channels during operation. Four weeks later, the effect of GDNF on axonal regeneration was evaluated by degenerative neurofiber staining and HRP retrograde tracing. Results: Compared with SAL group, the percentage of degenerative neurofiber areas decreased from 17.3% to 1.9% ( P<0.01 ) and the ratio of labeled spinal somas number was significantly increased from 43.5% to 68.3% ( P<0.01 ) in GDNF group. Conclusion: The results suggest that exogenous GDNF can obviously enhance adult peripheral nerve regeneration.

  11. Effects of Infantile Repeated Hyperglycemia on Behavioral Alterations in Adult Rats

    Directory of Open Access Journals (Sweden)

    Malihe Moghadami

    2012-09-01

    Full Text Available Anxiety symptoms have been reported to be present in many patients with diabetes mellitus. However, little is known about the effects of hyperglycemia in critical periods of the central nervous system development. We assessed locomotive, exploratory, and anxiety behaviors in adult rats that remained from infantile repeated hyperglycemia by the open field and elevated plus maze tests. Our findings showed significant hypo activity, reduced locomotive/exploratory activities, increased fear related behaviors, and anxiety state between hyperglycemic and control adult males and the same differences were observed among females. In addition, no significant behavioral alterations between male and female animals were observed. This study determined that repeated increments in daily blood sugar levels in newborns may affect neuronal functions and provide behavioral abnormalities in adults.

  12. Effect of maternal obesity on diabetes development in adult rat offspring.

    Science.gov (United States)

    de Campos, Kleber Eduardo; Sinzato, Yuri Karen; Pimenta, Walkyria de Paula; Rudge, Marilza Vieira Cunha; Damasceno, Débora Cristina

    2007-10-27

    This study aimed to evaluate whether maternal obesity leads to the onset of diabetes in adult Wistar rats offspring. MSG solution neonatally administration induced obesity in rats (F(1)MSG group, n=30); and saline solution was also administrated to control rats (F(1)CON group, n=13). In 3rd month of age, both control and MSG groups were mated for offspring (generation F(2)), named as F(2)CON, n=28 and F(2)MSG groups, n=15; and so both generations were studied until 7th month of life. Lee Index was measured for experimental obesity validation from 5th to 7th month. Glycemia was weekly determined during pregnancy and monthly from 3rd to 7th month. In the end of experimental period all rats were submitted to oral glucose tolerance test (OGTT), with estimation of total area under the curve (AUC); and insulin tolerance test (ITT). Rats were then anesthetized and killed. Data were statistically analyzed with significance level of pgenerations showed significant maternal interference in control and MSG groups. OGTT analysis showed higher glycemia in obese rats (F(1)MSG) and their offspring (F(2)MSG) as compared to their respective controls; and MSG groups increased AUC from OGTT. As regards ITT, F(2)MSG showed higher glycemia at 30 and 120 min, suggesting a delay of insulin action decreasing. Although glucose intolerance and insulin resistance clinical conditions represent as a factors for type 2 Diabetes mellitus development, this experimental model proposal was not efficient to induce type 2 Diabetes mellitus, but for obesity developing, glucose intolerance and insulin resistance in successive generations of rats.

  13. Alterations in cytochrome P-450 levels in adult rats following neonatal exposure to xenobiotics

    Energy Technology Data Exchange (ETDEWEB)

    Zangar, R.C. (Oregon State Univ., Corvallis (United States) Pacific Northwest Laboratories, Richland, WA (United States)); Springer, D.L. (Pacific Northwest Laboratories, Richland, WA (United States)); Buhler, D.R. (Oregon State Univ., Corvallis (United States))

    1993-01-01

    Neonatal exposure to certain xenobiotics has been shown to alter hepatic metabolism in adult rats in a manner that indicates long-term changes in enzyme regulation. Previously, the authors have observed changes in adult testosterone metabolism and in cytochrome P-450 (P-450) mRNA levels in animals neonatally exposed to phenobarbital (PB) or diethylstilbestrol (DES). In order to test for other enzyme alterations, they used Western blot procedures for specific P-450s to analyze hepatic microsomes from adult rats (24 wk old) that had been exposed neonatally to DES, PB, 7,12-dimethylbenz[a]anthracene (DMBA), or pregnenolone 16[alpha]-carbonitrile (PCN). The most striking effects were observed in the DES-treated males: P-4502C6 and an immunologically similar protein were increased 60 and 90%, respectively, relative to control values, but P-4503A2 was decreased by 44%. No changes were observed in the DES-treated males in levels of P-4502E1, P-4502B, or the male-specific P-4502C13. Adult males neonatally treated with PB had 150% increase in levels of anti-P4502B-reactive protein without significant changes in the other enzymes. The DES- and DMBA-treated females had increased levels of the female-specific P-4502C12 of 38 and 48%, respectively, but no other observed alterations. The results confirm that neonatal exposure to DES or PB can cause alterations in adult hepatic cytochrome P-450 levels but show that these chemicals act on different enzymes. Neonatal DMBA resulted in changes in adult females similar to those produced by the synthetic estrogen DES, but did so at about two-thirds lower dose. 37 refs., 5 figs.

  14. Environmental enrichment potentiates thalamocortical transmission and plasticity in the adult rat visual cortex.

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    Mainardi, Marco; Landi, Silvia; Gianfranceschi, Laura; Baldini, Sara; De Pasquale, Roberto; Berardi, Nicoletta; Maffei, Lamberto; Caleo, Matteo

    2010-11-01

    It has been demonstrated that the complex sensorimotor and social stimulation achieved by rearing animals in an enriched environment (EE) can reinstate juvenile-like plasticity in the adult cortex. However, it is not known whether EE can affect thalamocortical transmission. Here, we recorded in vivo field potentials from the visual cortex evoked by electrical stimulation of the dorsal lateral geniculate nucleus (dLGN) in anesthetized rats. We found that a period of EE during adulthood shifted the input-output curves and increased paired-pulse depression, suggesting an enhanced synaptic strength at thalamocortical terminals. Accordingly, EE animals showed an increased expression of the vesicular glutamate transporter 2 (vGluT-2) in geniculocortical afferents to layer IV. Rats reared in EE also showed an enhancement of thalamocortical long-term potentiation (LTP) triggered by theta-burst stimulation (TBS) of the dLGN. To monitor the functional consequences of increased LTP in EE rats, we recorded visual evoked potentials (VEPs) before and after application of TBS to the geniculocortical pathway. We found that responses to visual stimulation were enhanced across a range of contrasts in EE animals. This was accompanied by an up-regulation of the intracortical excitatory synaptic marker vGluT-1 and a decrease in the expression of the vesicular GABA transporter (vGAT), indicating a shift in the excitation/inhibition ratio. Thus, in the adult rat, EE enhances synaptic strength and plasticity of the thalamocortical pathway associated with specific changes in glutamatergic and GABAergic neurotransmission. These data provide novel insights into the mechanisms by which EE shapes the adult brain.

  15. Distinct Testicular Steroidogenic Response Mechanisms Between Neonatal and Adult Heat-Acclimated Male Rats

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    Beata Kurowicka

    2015-03-01

    Full Text Available Background: In comparison to short-term gonad heat exposure, little is known about the molecular mechanisms that regulate testicular steroidogenesis during long-term whole body heat acclimation. Material and Methods: Testicular slices from neonatal (NHA and adult (AHA heat-acclimated Wistar rats were analysed in vitro to assess the mRNA expression and enzymatic activity of steroidogenic enzymes under basal and luteinising hormone (LH or prolactin (PRL stimulated conditions compared with control rats (CR. Furthermore, a de-acclimated group (DA was created by transferring adult NHA rats to control conditions. Results: Heat acclimation significantly increased plasma LH levels in the AHA group and LH and PRL in the NHA group compared with the CR group; however, after heat acclimation, the T and E2 levels did not differ from the control levels. All heat-acclimated groups showed high basal intra-testicular steroid production in vitro. Moreover, basal Cyp11a1 and Hsd3b1 levels were upregulated in vitro in the NHA and DA groups versus the CR group. LH in vitro stimulation upregulated Cyp11a1 expression in the NHA and AHA groups and PRL stimulation upregulated Cyp17a1 levels in the NHA and DA groups compared with the basal expression levels. In the AHA group, decreased basal Star and CYP11A activities but increased HSD3B1 and CYP17A1 activities were found. Conclusion: Our data revealed that despite the similar steroid levels in plasma and secreted in vitro by neonatal and adult heat-acclimated rat testicular slices, the molecular mechanisms underlying the steroidogenic response to heat acclimation during these different developmental stages were distinct.

  16. A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus

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    Harish eBabu

    2011-07-01

    Full Text Available In vitro assays are valuable tools to study the characteristics of adult neural precursor cells under controlled conditions with a defined set of parameters. We here present a detailed protocol based on our previous original publication (Babu et al., Enriched monolayer precursor cell cultures from micro-dissected adult mouse dentate gyrus yield functional granule cell-like neurons, PLoS One 2007, 2:e388 to isolate neural precursor cells from the hippocampus of adult mice and maintain and propagate them as adherent monolayer cultures. The strategy is based on the use of Percoll density gradient centrifugation to enrich precursor cells from the micro-dissected dentate gyrus. Based on the expression of Nestin and Sox2, a culture-purity of more than 98% can be achieved. The cultures are expanded under serum-free conditions in Neurobasal A medium with addition of the mitogens EGF and FGF2 as well as the supplements Glutamax-1 and B27. Under differentiation conditions, the precursor cells reliably generate approximately 30% neurons with appropriate morphological, molecular and electrophysiological characteristics that might reflect granule cell properties as their in vivo counterpart. We also highlight potential modifications to the protocol.

  17. Impact of chronic nicotine administration on bone mineral content in young and adult rats: a comparative study.

    Science.gov (United States)

    Farag, Mahmoud M; Selima, Eman A; Salama, Mona A

    2013-11-15

    The aim of this study was to evaluate the effects of chronic nicotine administration on bone mineral homeostasis in rapidly growing young rats in comparison to effects in adult male rats. Two doses of nicotine (3 and 4.5mg/kg/day, as nicotine hydrogen tartrate) were used and rat treatment was continued for 6 months. In this study, all nicotine-treated rats weighed less than control rats and the effect was dose-dependent. Also, rats treated with nicotine had lower femoral wet weight and showed a significant reduction in femoral mid-shaft cortical width and femoral and lumbar vertebral ash weights. These effects were associated with a significant reduction of ash calcium and phosphorus contents of the femora and lumbar vertebrae. The bone mineral-lowering effects of nicotine were more severe in the lumbar vertebral spongy bone than in the femoral compact bone and these changes were more marked in adult rats than in young rats. An additional interesting observation was that the femora of young rats treated with nicotine were significantly shorter than those of control young rats. Also, the values of the femoral ash weight per unit length were significantly decreased in nicotine-treated adult rats but not in nicotine-treated young rats. Thus, these results show that nicotine-induced changes in bone vary with age. The clinical relevance of this study is that it may provide justification to insist that all people in general and the risky young group in particular should be warned against the hazards of the negative effects of nicotine on bone.

  18. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

    Science.gov (United States)

    van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

    2015-07-08

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

  19. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

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    Bert J. M. van de Heijning

    2015-07-01

    Full Text Available Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control. A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

  20. Cultured human embryonic neocortical cells survive and grow in infarcted cavities of adult rat brains and interconnect with host brain

    Institute of Scientific and Technical Information of China (English)

    ZENG Jin-sheng; YU Jian; CUI Chun-mei; ZHAO Zhan; HONG Hua; SHENG Wen-li; TAO Yu-qian; LI Ling; HUANG Ru-xun

    2005-01-01

    Background There are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains.Methods The right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation.Results Grafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded. Conclusion Cultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

  1. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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    A. Zago

    2012-01-01

    Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  2. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.

    Science.gov (United States)

    Jiang, Wen; Zhang, Yun; Xiao, Lan; Van Cleemput, Jamie; Ji, Shao-Ping; Bai, Guang; Zhang, Xia

    2005-11-01

    The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, G(i/o) proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.

  3. Application of Luxol Fast Blue staining in locating the corticospinal tract in adult rats

    Institute of Scientific and Technical Information of China (English)

    Su Liu; Guangyu Shen; Guangming Lü; Xiaosong Gu

    2006-01-01

    BACKGROUND: There are many methods for myelin staining,mordant,or the special reaction of osmic acid with lipoid is used according to different principles.The commonly used methods are classic Well staining ,classic lithium carbonate-haematine staining,fast green staining,silver staining ,etc.Luxol Fast Blue can brightly stain myelin sheath,and has certain specificity .The background can be very clean if there is proper differentiation,whereas Luxol Fast Blue is cheap and convenient to operate,thus it is an ideal staining reagent for routine myelin sheath.OBJECTIVE: To show the coricospinal tract of normal adult rats with Luxol Fast Blue shaining method.DESIGN:A repetitive measurement design.SETTINGS: Institute of Nuerobiology,Nantong University;Department of Rehabilitation Medicine,Affiliated Hospital of Nantong University.MATERIALS: Six healthy adult male SD rats of clean dergree,weighing averagely 300 g.were provided by the experimental animal center of Nantong University.1 g/L Luxol Fast Blue solution was provided by Sigma Company;Leica CM1900 cryostat microtome by Leica Company;Leica DMR microscope by Leica Company.METHODS:The experiment was carried out in the Staff Room of Human Anatomy,Nantong University in May 2005.The rats were given intraperitoneal injection of combined anesthetic(2 mL/kg),then the chest was open for perfusing saline and phosphate buffer containing formamint via heart. Brain and spinal cord were removed after 1 hour then fixed,then changed to phosphate buffer(pH 7.4)containing 300 g/L saccharu at 4 ℃.and stayed overnight,tissue blocks at pyramid,decussation of pyramid and cervical,thoracic,lumbar and sacral segments of spinal cord were removed to prepare continuous horizontal frozen sections(30 μm) after sedimentation,the sections were dried at room temperature.The corticospinal tract of normal adult rats were shown with Luxol Fast Blue staining method,and observed under Leica DMR microscope.MAIN OUTCOME MEASURES:Positive fibers in

  4. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  5. Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition.

    Science.gov (United States)

    Engler-Chiurazzi, Elizabeth B; Stapleton, Phoebe A; Stalnaker, Jessica J; Ren, Xuefang; Hu, Heng; Nurkiewicz, Timothy R; McBride, Carroll R; Yi, Jinghai; Engels, Kevin; Simpkins, James W

    2016-01-01

    It is generally accepted that gestational xenobiotic exposures result in systemic consequences in the adult F1 generation. However, data on detailed behavioral and cognitive consequences remain limited. Using our whole-body nanoparticle inhalation facility, pregnant Sprague-Dawley rats (gestational day [GD] 7) were exposed 4 d/wk to either filtered air (control) or nano-titanium dioxide aerosols (nano-TiO2; count median aerodynamic diameter of 170.9 ± 6.4 nm, 10.4 ± 0.4 mg/m(3), 5 h/d) for 7.8 ± 0.5 d of the remaining gestational period. All rats received their final exposure on GD 20 prior to delivery. The calculated daily maternal deposition was 13.9 ± 0.5 µg. Subsequently, at 5 mo of age, behavior and cognitive functions of these pups were evaluated employing a standard battery of locomotion, learning, and anxiety tests. These assessments revealed significant working impairments, especially under maximal mnemonic challenge, and possible deficits in initial motivation in male F1 adults. Evidence indicates that maternal engineered nanomaterial exposure during gestation produces psychological deficits that persist into adulthood in male rats.

  6. Effect of pinealectomy, adrenalectomy, pinealectomy plus adrenalectomy upon the quantification of spermatogenic cells of adult rats

    Directory of Open Access Journals (Sweden)

    Castro A.C.S.

    2002-01-01

    Full Text Available The objectives of this study were to evaluate the effects of pinealectomy, adrenalectomy and pinealectomy-adrenalectomy upon the quantification of spermatogenic cells of rats. As such, 32 adult Wistar rats with a mean body weight of 331.7± 15.5g were assigned into one of the following treatments: (a a sham-operated control group, consisting of nine animals; (b ten pinealectomized animals; (c seven adrenalectomized animals and (d six pinealectomized plus adrenalectomized animals. No significant differences were observed between groups for the following parameters: body, testes, prostate and seminal vesicle weights, seminiferous tubular diameter, number of cells per seminiferous tubular cross sections (primary spermatocytes at pachytene, round spermatids, Sertoli cells and numbers of germ cells per Sertoli cell (primary spermatocytes at pachytene and round spermatids . Although no increase in testicular weight was observed following pinealectomy, a significant (P<0.05 increase of approximately 11.5% in the number of round spermatids per Sertoli cell (Sertoli cell ratio occurred thus suggesting that short-term pinealectomy abolishes the antigonadal effect of the pineal gland upon adult Wistar rat testes.

  7. Variability in the distribution of callosal projection neurons in the adult rat parietal cortex.

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    Ivy, G O; Gould, H J; Killackey, H P

    1984-07-23

    Previous reports have shown that the barrel field area of the parietal cortex of the adult rat contains relatively few callosal projection neurons, even though callosal projection neurons are abundant in this cortical region in the neonatal rat. Furthermore, it has been shown that many of the callosal neurons which seem to disappear as the animal matures do not die, but project to ipsilateral cortical areas. These findings rely on the ability of retrograde transport techniques which utilize injections of horseradish peroxidase (HRP) or of fluorescent dyes into one hemisphere. We now show that several technical modifications of the HRP technique yield a wider distribution of HRP-containing neurons in the contralateral barrel field area of the adult rat than previously reported. These include implants of HRP pellets into transected axons of the corpus callosum, the addition of DMSO and nonidet P40 to Sigma VI HRP, wheat germ agglutinin HRP and the use of tetramethyl benzidine as the chromogen in the reaction procedure. Our findings have implications for transport studies in general and for the development of the cortical barrel field in particular.

  8. Effects of moderate zinc deficiency on cognitive performance in young adult rats.

    Science.gov (United States)

    Massaro, T F; Mohs, M; Fosmire, G

    1982-07-01

    Two experiments were conducted to establish a dietary zinc level which approximates a moderate deficiency in the young adult rat and to determine if a concurrent zinc deficiency affects cognitive performance. Male rats were fed varying levels of zinc in diet throughout a 17-day period. The lowest dietary level that depressed serum and bone zinc without influencing food consumption or body weight gains was observed to be 5.8 microgram Zn/g diet. Young adult rats maintained on either a zinc adequate (24.4 microgram Zn/g) or low-zinc (5.3 microgram Zn/g) diet were tested in a modified Skinner Box involving tests of visual, auditory, association, and discrimination learning. No differences were observed in the visual discrimination performance of the zinc deficient animals when compared with control counterparts. Deficits in the ability to transfer a learned association between visual and auditory stimuli were observed, however, in the deficient group during the transfer test phase. The latter performed better during the final auditory discrimination task in transferring a learned food-relevant cue.

  9. Fluoxetine enhanced neurogenesis is not translated to functional outcome in stroke rats.

    Science.gov (United States)

    Sun, Xiaoyu; Sun, Xuan; Liu, Tingting; Zhao, Mei; Zhao, Shanshan; Xiao, Ting; Jolkkonen, Jukka; Zhao, Chuansheng

    2015-08-31

    Fluoxetine is widely used in clinical practice. It regulates hippocampal neurogenesis, however, the effect of fluoxetine on neurogenesis in the subventricular zone (SVZ) remains controversial. We aimed to study the effect of fluoxetine on neurogenesis in the SVZ and subgranular zone (SGZ) of dentate gyrus (DG) in relation to behavioral recovery after stroke in rats. Adult male Wistar rats were randomly assigned to four groups: sham-operated rats, sham-operated rats treated with fluoxetine, rats subjected to cerebral ischemia, and rats with ischemia treated with fluoxetine. Fluoxetine was orally administrated starting 1 week after ischemia, with a dose of 16mg/kg/day for 3 weeks. Focal cerebral ischemia was induced by intracranial injection of vasoconstrictive peptide endothelin-1(ET-1). Behavioral recovery was evaluated on post-stroke days 29-31 after which the survival rate and fate of proliferating cells in the SVZ and DG were measured by immunohistochemistry. The production of neuroblasts in both the SVZ and DG was significantly increased after stroke. Chronic post-stroke fluoxetine treatment increased the dendritic complexity of newborn dentate granule cells. However, fluoxetine treatment did not influence the survival or differentiation of newly generated cells. Neither fluoxetine treatment improved sensorimotor recovery following focal cerebral ischemia.

  10. Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

    Science.gov (United States)

    Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

    2015-07-01

    Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood.

  11. Protective effects of vitamin E and selenium on spermatogenesis in adult male rat insulin-resistant

    Directory of Open Access Journals (Sweden)

    Alireza Zakerabasali

    2013-03-01

    Full Text Available Background & Objective: Diabetes mellitus is a metabolic disease and is a multifactorial disorder characterized by chronic hyperglycemia resulting from impaired insulin secretion and insulin factional or both. In this study, the protective role of vitamin E and sodium selenite in preventing the harmful effects of insulin resistance (diabetes type 2 on spermatogenesis was studied.   Materials & Methods: Male adults (180-200 g of Wistar rats were divided into five groups, each containing 7 rats (control, sham, and three experimental groups. The rats were fed daily with water-soluble fructose (10%, mg/kg 200 of vitamin E (gavage, and 5/0 mg/kg of sodium selenite (intraperitoneal injection or both for 110 days. Subsequently, sperm parameters, levels of testosterone, LH, and daily sperm production (DSP were checked. Additionally, testicular histopathology and malondialdehyde (MDA in the testis were examined.   Results: Sperm count, sperm motility and viability, and insulin resistance in the rats decreased DSP. A significant decrease was observed in the number of Leydig cells, spermatogonia, spermatogenesis, and spermatozoa in the testis of the insulin-resistant animals, whereas MDA and testosterone rose in the insulin-resistant rats. Vitamin E and sodium selenite intake reduced the levels of MDA and harmful effects of fructose on testicles, as well as sperm parameters and testicular pathology. A simultaneous intake of vitamin E and sodium selenite conferred the highest level of protection.   Conclusion: These findings suggest that vitamin E and sodium selenite can have a protective role in the testes of rats against oxidative stress induced by diabetes type 2.

  12. Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.

    Science.gov (United States)

    Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín, Luis Javier; De Fonseca, Fernando Rodríguez; Capani, Francisco; Blanco, Eduardo

    2013-09-01

    Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction.

  13. Ependymal cell proliferation and apoptosis following acute spinal cord injury in the adult rat

    Institute of Scientific and Technical Information of China (English)

    Xu Wang; Jun Qian; Yanchao Ma; Guoxin Nan; Shuanke Wang; Yayi Xia; Youcheng Zhang

    2008-01-01

    BACKGROUND: Studies have reported that spinal cord injury can induce the reactive proliferation of ependymal cells and secondarily cause the apoptosis of nerve cells. However, there is no generally accepted theory on the apoptotic characteristics of ependymal cells in the injured spinal cord.OBJECTIVE: To observe the reactive proliferation and apoptosis of ependymal cells in adult rats following acute spinal cord injury.DESIGN, TIME AND SETTING: A randomized control study based on neuropathology was performed in the Third Military Medical University of Chinese PLA between 2005 and 2007.MATERIALS: Forty healthy, adult, Wistar rats were included in the present study.METHODS: Moderate spinal cord injury was established in twenty rats using Feeney's method, while the remaining 20 rats served as controls and were only treated with laminectomy. All rats were injected intraperitoneally with 1.25 mL of BrdU solution (10 mg BrdU/mL saline) 3 times at 4 hours intervals during the 12 hours prior to sacrifice.MAIN OUTCOME MEASURES: Ependymal cell proliferation and apoptosis in the rat spinal cord were determined by BrdU and nestin immunofluorescence double-labeling, as well as the TUNEL method, at 1, 3, 7, and 14 days after operation.RESULTS: In the moderate spinal cord injury rats, nestin expression was observed in the cytoplasm of ependymal cells. One day immediately following surgery, ependymal cells were BrdU-labeled. The number of BrdU-positive cells increased at 3 days, reached a peak at 7 days, and gradually reduced thereafter. The ependyma developed ti'om a constitutive monolayer cells to a multi-layer cell complex. Some BrdU/Nestin double-positive ependymal cells migrated out from the ependyma. TUNEL-positive cells were also detected in the ependyma in the central region, as well as ischemic regions of the injured spinal cord. In addition, TUNEL-positive cells were visible in the ependyma. No TUNEL-positive ependymal cells were observed in the normal spinal cord

  14. MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors.

    Science.gov (United States)

    Collins, Stuart A; Gudelsky, Gary A; Yamamoto, Bryan K

    2015-08-15

    MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation.

  15. Sodium metabisulfite-induced changes on testes, spermatogenesis and epididymal morphometric values in adult rats

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    Shahnaz Shekarforoush

    2015-12-01

    Full Text Available Background: Sulphites are widely used as a preservative and antioxidant additives in the food and pharmaceutical industries. Many types of biological and toxicological effects of sulphites in multiple organs of mammals have been shown in previous studies. Objective: The aim of this study was to investigate the effects of sodium metabisulfite (SMB on testicular function and morphometric values of epididymis in adult male Wistar rats. Materials and Methods: A total of 32 rats were randomly divided into four groups. The experimental groups received SMB at doses of 10 mg/kg (S10, 100mg/kg (S100, and 260 mg/kg (S260 while an equal volume of normal saline was administered to the control group via gavage. The rats were anaesthetized after 28 days and the left testis with the head of epididimis was excised following abdominal incision for histological observation using hematoxylin and eosin staining. Serum samples were collected for assay of testosterone level. The initial epididymis was analyzed for motility, morphology, and the number of sperms. Result: The results of this study showed that normal morphology, count, and motility of sperms and testosterone level were decreased in the SMB treated groups. In comparison with the control group, SMB resulted in a lower total number of spermatogonia, primary spermatocyte, spermatids, and Leydig cells. Conclusion: It is suggested that SMB decreases the sperm production and has the potential to affect the fertility adversely in male rats.

  16. Sugar overconsumption during adolescence selectively alters motivation and reward function in adult rats.

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    Leandro F Vendruscolo

    Full Text Available BACKGROUND: There has been a dramatic escalation in sugar intake in the last few decades, most strikingly observed in the adolescent population. Sugar overconsumption has been associated with several adverse health consequences, including obesity and diabetes. Very little is known, however, about the impact of sugar overconsumption on mental health in general, and on reward-related behavioral disorders in particular. This study examined in rats the effects of unlimited access to sucrose during adolescence on the motivation for natural and pharmacological rewards in adulthood. METHODOLOGY/PRINCIPAL FINDINGS: Adolescent rats had free access to 5% sucrose or water from postnatal day 30 to 46. The control group had access to water only. In adulthood, rats were tested for self-administration of saccharin (sweet, maltodextrin (non-sweet, and cocaine (a potent drug of abuse using fixed- and progressive-ratio schedules, and a concentration-response curve for each substance. Adult rats, exposed or not exposed to sucrose, were tested for saccharin self-administration later in life to verify the specificity of adolescence for the sugar effects. Sugar overconsumption during adolescence, but not during adulthood, reduced the subsequent motivation for saccharin and maltodextrin, but not cocaine. This selective decrease in motivation is more likely due to changes in brain reward processing than changes in gustatory perception. CONCLUSIONS/SIGNIFICANCE: Sugar overconsumption induces a developmental stage-specific chronic depression in reward processing that may contribute to an increase in the vulnerability to reward-related psychiatric disorders.

  17. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study

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    Norman Ruthven Saunders

    2015-04-01

    Full Text Available The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analysed by functional groups of influx transporters, particularly solute carrier (SLC transporters. RNA-Seq was performed at embryonic day (E 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve with expression levels 2-98 times greater than in the adult. In contrast, in the adult only six amino acid transporters were up-regulated compared to the embryo and at more modest enrichment levels (<5-fold enrichment above E15. In E15 plexus five glucose transporters, in particular Glut-1, and only one monocarboxylate transporter were enriched compared to the adult, whereas only two glucose transporters but six monocarboxylate transporters in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing brain with higher amino acid transport activity reported previously. Data for divalent metal transporters are also considered. Immunohistochemistry of several transporters (e.g. Slc16a10, a thyroid hormone transporter gene products was carried out to confirm translational activity and to define cellular distribution of the proteins. Overall the results show that there is substantial expression of numerous influx transporters in the embryonic choroid plexus, many at higher levels than in the adult. This, together with immunohistochemical evidence and data from published physiological transport studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients.

  18. Constituent ratio of motor fibers from the C5-C7 spinal nerves in the radial nerve is greater in pup rats than in adult rats.

    Science.gov (United States)

    Nie, Mingbo; Chen, Liang; Gu, Yudong

    2012-06-01

    Clinically, injuries of C5-C7 of the brachial plexus cause falling of the wrist and fingers in infants but not in adults unless 4 consecutive spinal nerves are injured. The purpose of this study was to compare the constituent difference of spinal nerves in the radial nerve between pup and adult rats.A group of 16 pup rats and a group of 16 adult rats were each divided into 2 groups of 8 (P1 and A1 groups, C5-C6 were divided; P2 and A2 groups, C5-C7 were divided]). A nerve conduction study and histological examination were performed to evaluate radial nerve innervation to the extensor digitorum communis muscle after dividing the spinal nerves. Retrograde tracing with 5% cholera toxin B for anterior horn motoneurons of the spinal cord innervating the radial nerve was performed in 8 pup rats and 8 adult rats. Results showed that the division of C5-C7 caused more significant damage to radial nerve innervation to the extensor digitorum communis in pups than in adults, although the division of C5-C6 did not. In pups, the percentages (median with interquartile) of anterior horn motoneurons of the spinal cord innervating the radial nerve were 36.4 (28.3-38.5) in C5-C6, 28.1 (24.5-32.5) in C7, and 37.5 (36.5-39.3) in C8-T1. In adults, they were 24.2 (23.6-27.8) in C5-C6, 21.8 (19.5-26.3) in C7, and 50.7 (48.7-55.5) C8-T1.This study implies that C7 innervation in the radial nerve in humans may be more critical to the function of this nerve in infants than in adults.

  19. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    Science.gov (United States)

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs.

  20. CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT RAT HIPPOCAMPUS BUT DOES NOT IMPAIR SPATIAL LEARNING.

    Science.gov (United States)

    It has long been heralded that the mature brain does not generate new neurons, it only loses them as a function of injury, disease and age. An exciting recent finding in neuroscience has been that the dentate granule cell layer of the hippocampus has the distinctive property of ...

  1. Long-term effects of repeated maternal separation and ethanol intake on HPA axis responsiveness in adult rats.

    Science.gov (United States)

    Odeon, María Mercedes; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2017-02-15

    It has been shown that early life manipulations produce behavioral, neural, and hormonal effects. The long term consequences of repeated maternal separation (RMS) plus cold stress and ethanol intake were evaluated during adolescence and adult rats on hypothalamic-pituitary-adrenal (HPA) axis in male adult Wistar rats. RMS+ cold stress was applied from postnatal day (PD) 2 in which the pups were separated from their mothers and exposed to cold stress (4°C) 1h per day for 20days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7days: PD22-29 and PD59-66. Half of the animals were sacrificed, while the others were exposed to acute stress (AS) for 2h and then they were killed. RMS+ cold stress: a) increased voluntary ethanol intake in adolescent and adult rats; b) reduced protein expression (Western measurements) in corticotropin-releasing hormone (CRH) in hypothalamus (Hyp) and mineralocorticoid receptor (MR) in hippocampus (Hic) while increased glucocorticoid receptor (GR) in Hic; c) decreased plasmatic levels of adrenocorticotropic hormone (ACTH) and increased corticosterone (COR) levels in HPA axis, d) adult rats exposure a new AS incremented ACTH and COR levels. However, this modification did not alter the HPA axis capacity to respond to a new type of stressor. These results demonstrate the consequences of early life stress on the vulnerability of ethanol consumption and HPA axis responsiveness to a stressor in adult rats.

  2. Histological changes in kidneys of adult rats treated with Monosodium glutamate: A light microscopic study

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    Singh BR, Ujwal Gajbe, Anil Kumar Reddy, Vandana Kumbhare

    2015-01-01

    Full Text Available Introduction: Monosodium Glutamate (MSG, which is chemically known as AJI-NO-MOTO also familiar as MSG in routine life. MSG is always considered to be a controversial food additive used in the world. It is a natural excitatory neurotransmitter, helps in transmitting the fast synaptic signals in one third of CNS. Liver and kidney play a crucial role in metabolism as well as elimination of MSG from the body. Present study is to detect structural changes in adult rat kidney tissue treated with MSG; observations are done with a light microscope. Materials & Methods: The study was conducted in the department of Anatomy, J.N.M.C, Sawangi (M Wardha. Thirty (30 adult Wistar rats (2-3 months old weighing about (200 ± 20g were used in the current study, animals were divided into three groups (Group – A, B, C. Group A: Control, Group B: 3 mg /gm body weight, Group C: 6 mg /gm body weight, MSG were administered orally daily for 45 days along with the regular diet. Observations & Results: The Mean values of animals weight at the end of experiment (46th day respectively were 251.2 ± 13, 244.4 ± 19.9 and 320 ± 31.1. Early degenerative changes like, Glomerular shrinkage (GSr, loss of brush border in proximal convoluted tubules and Cloudy degeneration was observed in sections of kidney treated with 3 mg/gm body weight of MSG. Animals treated with 6 mg/gm body weight of MSG showed rare changes like interstitial chronic inflammatory infiltrate with vacuolation in some of the glomeruli, and much glomerular shrinkage invaginated by fatty lobules. Conclusion: The effects of MSG on kidney tissues of adult rats revealed that the revelatory changes are directly proportional to the doses of MSG.

  3. Neonatal stress tempers vulnerability of acute stress response in adult socially isolated rats

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    Mariangela Serra

    2014-06-01

    Full Text Available Adverse experiences occurred in early life and especially during childhood and adolescence can have negative impact on behavior later in life and the quality of maternal care is considered a critical moment that can considerably influence the development and the stress responsiveness in offspring. This review will assess how the association between neonatal and adolescence stressful experiences such as maternal separation and social isolation, at weaning, may influence the stress responsiveness and brain plasticity in adult rats. Three hours of separation from the pups (3-14 postnatal days significantly increased frequencies of maternal arched-back nursing and licking-grooming by dams across the first 14 days postpartum and induced a long-lasting increase in their blood levels of corticosterone. Maternal separation, which per sedid not modified brain and plasma allopregnanolone and corticosterone levels in adult rats, significantly reduced social isolation-induced decrease of the levels of these hormones. Moreover, the enhancement of corticosterone and allopregnanolone levels induced by foot shock stress in socially isolated animals that were exposed to maternal separation was markedly reduced respect to that observed in socially isolated animals. Our results suggest that in rats a daily brief separation from the mother during the first weeks of life, which per se did not substantially alter adult function and reactivity of hypothalamic-pituitary-adrenal (HPA axis, elicited a significant protection versus the subsequent long-term stressful experience such that induced by social isolation from weaning. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in NeonatologyGuest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  4. Nitric oxide negatively regulates mammalian adult neurogenesis

    Science.gov (United States)

    Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

    2003-08-01

    Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

  5. Increased astrocytic expression of metallothioneins I + II in brainstem of adult rats treated with 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan; Moos, Torben

    1997-01-01

    The cerebral distribution of metallothioneins I and II (MT-I + II) was studied in adult rats subjected to i.p. injection with the gliotoxin 6-aminonicotinamide (6-AN). Grey matter regions of the brainstem heralded numerous OX-42-positive macrophages and microglia, indicating that 6-AN primarily...... caused damage to this part of the brain. In the grey matter regions infiltrated with OX-42-positive cells, astrocytes identified by anti-GFAP and MT-I + II antibodies were almost absent. By contrast, in the peripheral zone of the lesioned regions numerous reactive GFAP- and MT-I + II-positive astrocytes...

  6. Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats

    Energy Technology Data Exchange (ETDEWEB)

    Gaspar, Andréia Fresneda [Departamento de Farmacologia, Instituto de Biociências - Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Faculdade da Alta Paulista (FAP), Tupã, SP (Brazil); Cordellini, Sandra, E-mail: cordelli@ibb.unesp.br [Departamento de Farmacologia, Instituto de Biociências - Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil)

    2014-09-15

    Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension.

  7. Suspension of Mitotic Activity in Dentate Gyrus of the Hibernating Ground Squirrel

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    Victor I. Popov

    2011-01-01

    Full Text Available Neurogenesis occurs in the adult mammalian hippocampus, a region of the brain important for learning and memory. Hibernation in Siberian ground squirrels provides a natural model to study mitosis as the rapid fall in body temperature in 24 h (from 35-36°C to +4–6°C permits accumulation of mitotic cells at different stages of the cell cycle. Histological methods used to study adult neurogenesis are limited largely to fixed tissue, and the mitotic state elucidated depends on the specific phase of mitosis at the time of day. However, using an immunohistochemical study of doublecortin (DCX and BrdU-labelled neurons, we demonstrate that the dentate gyrus of the ground squirrel hippocampus contains a population of immature cells which appear to possess mitotic activity. Our data suggest that doublecortin-labelled immature cells exist in a mitotic state and may represent a renewable pool for generation of new neurons within the dentate gyrus.

  8. The CA3 "backprojection" to the dentate gyrus.

    Science.gov (United States)

    Scharfman, Helen E

    2007-01-01

    The hippocampus is typically described in the context of the trisynaptic circuit, a pathway that relays information from the perforant path to the dentate gyrus, dentate to area CA3, and CA3 to area CA1. Associated with this concept is the assumption that most hippocampal information processing occurs along the trisynaptic circuit. However, the entorhinal cortex may not be the only major extrinsic input to consider, and the trisynaptic circuit may not be the only way information is processed in hippocampus. Area CA3 receives input from a variety of sources, and may be as much of an "entry point" to hippocampus as the dentate gyrus. The axon of CA3 pyramidal cells targets diverse cell types, and has commissural projections, which together make it able to send information to much more of the hippocampus than granule cells. Therefore, CA3 pyramidal cells seem better designed to spread information through hippocampus than the granule cells. From this perspective, CA3 may be a point of entry that receives information which needs to be "broadcasted," whereas the dentate gyrus may be a point of entry that receives information with more selective needs for hippocampal processing. One aspect of the argument that CA3 pyramidal cells have a widespread projection is based on a part of its axonal arbor that has received relatively little attention, the collaterals that project in the opposite direction to the trisynaptic circuit, "back" to the dentate gyrus. The evidence for this "backprojection" to the dentate gyrus is strong, particularly in area CA3c, the region closest to the dentate gyrus, and in temporal hippocampus. The influence on granule cells is indirect, through hilar mossy cells and GABAergic neurons of the dentate gyrus, and appears to include direct projections in the case of CA3c pyramidal cells of ventral hippocampus. Physiological studies suggest that normally area CA3 does not have a robust excitatory influence on granule cells, but serves instead to inhibit

  9. Impairment on sperm quality and fertility of adult rats after antiandrogen exposure during prepuberty.

    Science.gov (United States)

    Perobelli, Juliana Elaine; Alves, Thaís Regina; de Toledo, Fabíola Choqueta; Fernandez, Carla Dal Bianco; Anselmo-Franci, Janete A; Klinefelter, Gary R; Kempinas, Wilma De Grava

    2012-06-01

    This study evaluated the effects of antiandrogen exposure during the prepubertal period on reproductive development and reproductive competence in adults. Male rats were divided into two groups: flutamide, receiving 25 mg/kg/day of flutamide by oral gavage and control, receiving vehicle daily. Dosing continued from PND 21 to 44, and animals were killed on PND 50 or PND 75-80. The epididymis, prostate, vas deferens and seminal vesicle weights were lower in Flutamide group on PND 50, while on PND 80 only seminal vesicle weight was reduced. Fertility assessed by IUI revealed a decrease in the fertility potential in the flutamide-treated adults. Flutamide accelerated sperm transit time through the epididymis, impairing sperm motility and storage. A quantitative analysis of the cauda sperm membrane proteome revealed a few significant changes in protein expression. Thus, exposure to flutamide during the prepubertal period compromises the function of the epididymis along with epididymal sperm quality at adulthood.

  10. The cortical response to sensory deprivation in adult rats is affected by gonadectomy.

    Science.gov (United States)

    Mowery, Todd M; Elliott, Kevin S; Garraghty, Preston E

    2009-05-01

    The present study investigated the effects of adult-onset sensory deprivation and gonadectomy. Adult male and female rats underwent unilateral transection of the infraorbital nerve. Half of the subjects had been gonadectomized 1 week prior to the nerve injury. We found that the areas of deprived barrels were significantly reduced when compared to barrels in the contralateral control hemisphere, and that this shrinkage was independent of sex and gonadectomy. We also found significant reductions in cytochrome oxidase staining intensity in the deprived barrels. While there were no differences in the magnitude of this effect between males and females, this effect was substantially more pronounced in the gonadectomized subjects. That is, gonadal hormones appeared to play a significant neuroprotective role in the metabolic response of the barrel cortex to deprivation. Thus, either males and females have a common neuroprotective hormonal pathway, or each has a sex-specific hormone pathway that serves an equivalent neuroprotective function.

  11. Reproducible isolation of type II pneumocytes from fetal and adult rat lung using nycodenz density gradients.

    Science.gov (United States)

    Viscardi, R M; Ullsperger, S; Resau, J H

    1992-01-01

    Isolating fresh, relatively pure type II pneumocytes from the lung, particularly of fetal origin, is a difficult process. Separation by buoyant density gradient centrifugation has been used successfully to isolate adult type II cells. There is concern, however, that Percoll, a gradient medium that is commonly used for type II cell isolation, may be toxic to cells. We evaluated a new gradient medium, Nycodenz, that is (1) a true solution, (2) transparent, (3) not metabolized by cells, and (4) nontoxic to cells. Type II pneumocytes were isolated from 19- and 21-day gestation fetal and adult rat lung by elastase digestion and separated on preformed isotonic Nycodenz gradients (2 mL each of 27.6, 20.7, 13.8, and 4.6 (w/v) solutions). Type II pneumocytes were recovered from the density range 1.057-1.061 and identified by binding of FITC-conjugated and gold-complexed Maclura pomifera lectin. Cells derived from 19-day fetal lung contained abundant glycogen and reacted with a monoclonal antibody to the cytokeratins 8 and 18, which are markers of the fetal type II cell. Adult type II cells reacted with antibodies to cytokeratins 8, 18, and 19. Type II cell purity was 79.7 +/- 2.4%, 83.8 +/- 2.8%, and 82.6 +/- 1.8% (means +/- SEM) for 19- and 21-day gestation fetal and adult lung preparations, respectively. Cell viability was greater than 95%. The final cell yield for adult preparations was 17.8 +/- 2.7 x 10(6)/rat (means +/- SEM). To determine if the freshly isolated type II pneumocytes were functionally active, the incorporation of [3H]choline into phosphatidylcholine was measured. The percent saturation of phosphatidylcholine was high for both populations of freshly isolated cells. However, adult type II pneumocytes incorporated [3H]choline into phosphatidylcholine more rapidly than 21-day gestation fetal cells (5.97 x 10(-3) dpm/10(6) cells/h vs. 0.32 x 10(-3) dpm/10(6) cells/h, P less than .005). We have demonstrated that, using the Nycodenz isolation method, it is

  12. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    Science.gov (United States)

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  13. Ovariectomy results in variable changes in nociception, mood and depression in adult female rats.

    Directory of Open Access Journals (Sweden)

    Li-Hong Li

    Full Text Available Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, depressive-like and learning behaviors in experimental rats after ovariectomy (OVX, a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%-induced nociceptive responses (such as elevating and licking or biting during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact. Using formalin-induced conditioned place avoidance (F-CPA, which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA. In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way.

  14. Ethidium bromide-induced demyelination of the sciatic nerve of adult Wistar rats

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    Riet-Correa G.

    2002-01-01

    Full Text Available Peripheral nerve ultrastructure was assessed after single or multiple local injections of the intercalating dye ethidium bromide. Thirty-four adult Wistar rats of both sexes were divided into five groups and maintained in a controlled environment with rat chow and water ad libitum throughout the experiment. The experimental animals were injected with 1 µl of 0.1% ethidium bromide in 0.9% saline into the central third of the left sciatic nerve 1 (group 1, 2 (group 2, 4 (group 3, 6 (group 4 or 8 (group 5 times. In groups 2 to 5 the injections were made at 28-day intervals. Control animals received the same amount of 0.9% saline. The animals were killed at different times after injection: group 1 at 7 days (2 rats and 15 days (2 rats; for groups 2, 3, 4 and 5, all rats were killed 10 days after the last injection and the lesions were investigated by light and transmission electron microscopy. In the acute lesions, intoxicated Schwann cells showed a vacuolated cytoplasm and separation of the sheaths from the axon. Myelin sheaths underwent progressive vesiculation and subsequent segmental demyelination. Myelin debris were withdrawn by macrophages and remyelination by Schwann cells was prominent. With the increase in the number of injections collagen fibers also increased in number and progressively enveloped smaller numbers of remyelinated axons composing new fascicles. Wallerian degeneration of fibers apparently not affected by ethidium bromide was more intense in the nerves from groups 4 and 5. The peripheral nerve repairs itself after demyelinating challenges with a profusion of collagen fibers and new fasciculations. This experimental model is valid to mimic recurrent demyelinating neuropathies.

  15. The social behavior of male rats administered an adult-onset calorie restriction regimen.

    Science.gov (United States)

    Govic, Antonina; Levay, Elizabeth A; Kent, Stephen; Paolini, Antonio G

    2009-03-23

    The behavioral outcomes of a calorie restricted diet are often neglected in favour of a more physiological examination of the consequences of calorie restriction (CR). This is especially the case with social behavior. A few findings within the maternal CR literature suggest that adult male social behavior is altered by this regimen. Despite the paucity of findings within the maternal CR literature, a systematic investigation of the behavioral phenotype of males administered an adult-onset CR is completely lacking and was the focus of the current study. Adult male hooded Wistar rats were administered a three week CR, with one group receiving a 25% CR and another group receiving a 50% CR before male-to-male social behavior was examined and compared with ad libitium fed males. Various behavioral elements were modulated by CR, both the CR25% and 50% group initiated contact sooner and engaged in greater social activity compared to the ad libitum fed controls. The CR25% group also demonstrated less non-social (self-grooming) behavior and a greater frequency of walkovers compared to all groups, indicating a propensity towards dominance. The CR50% group demonstrated greater environmental assessment/exploration, as measured by the frequency of rearing. As with the maternal CR literature, an adult-onset chronic CR induces a more socially active behavioral phenotype and reduces interest in non-social behavior in the moderately CR group. Taken together, the social behavioral phenotype can be modulated by a CR initiated and maintained during adulthood.

  16. Immunohistochemical distribution of Plexin A4 in the adult rat central nervous system

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    Claire-Anne Gutekunst

    2010-07-01

    Full Text Available PlexinA4 is the latest member to be identified of the plexin A subfamily, critical transducers of class 3 semaphorin signaling as co-receptors to neuropilins 1 and 2. Despite functional information regarding the role of PlexinA4 in development and guidance of specific neuronal pathways, little is known about its distribution in the adult central nervous system (CNS. Here we report an in depth immunohistochemical analysis of PlexinA4 expression in the adult rat CNS. PlexinA4 staining was present in neurons and fibers throughout the brain and spinal cord, including neocortex, hippocampus, lateral hypothalamus, red nucleus, facial nucleus and the mesencephalic trigeminal nucleus. PlexinA4 antibodies labeled fibers in the lateral septum, nucleus accumbens, several thalamic nuclei, substantia nigra pars reticulata, zona incerta, pontine reticular region, as well as in several cranial nerve nuclei. This constitutes the first detailed description of the topographic distribution of PlexinA4 in the adult CNS and will set the basis for future studies on the functional implications of PlexinA4 in adult brain physiology.

  17. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits

    Institute of Scientific and Technical Information of China (English)

    Donnahue; Dennie; Jean-Pierre; Louboutin; David; S; Strayer

    2016-01-01

    Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory bulb.Different molecular markers can be used to characterizethe cells involved in adult neurogenesis.It has been recently suggested that a population of bone marrow(BM)progenitor cells may migrate to the brain and differentiate into neuronal lineage.To explore this hypothesis,we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells.Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells,then after several months in mature neurons and microglial cells,and thus without central nervous system(CNS)lesion.Most of transgene-expressing cells expressed NeuN,a marker of mature neurons.Thus,BM-derived cells may function as progenitors of CNS cells in adult animals.The mechanism by which the cells from the BM come to be neurons remains to be determined.Although the observed gradual increase in transgene-expressing neurons over 16mo suggests that the pathway involved differentiation of BM-resident cells into neurons,cell fusion as the principal route cannot be totally ruled out.Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons.Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector.In addition to cells expressing markers of mature neurons,transgene-positive cells were also positive for nestin and doublecortin,molecules expressed by developing neuronal cells.These cells were actively proliferating,as shown by short term BrdU incorporation studies.Inducing seizures by using kainic acid increased the number of BM progenitor cells transduced by SV40vectors

  18. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.

    Science.gov (United States)

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-04-26

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  19. Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats

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    Alireza Sarkaki

    2013-09-01

    Full Text Available   Objective(s: Cerebral hypoperfusion/ischemia (CHI is a neurological disease where impaired hippocampus electrical activity and cognition caused by a serial pathophysiological events. This study aimed to evaluate the effects of chronic oral administration of grape seed extract (GSE on passive avoidance memory and long-term potentiation (LTP after permanent bilateral common carotid arteries occlusion (2CCAO in male adult rats.   Materials and Methods: Thirty-two adult male Wistar rats were randomly divided into: 1 Sham+Veh, 2 Isch+Veh, 3 Sham+GSE, 4 Isch+GSE. In order to make 2CCAO as an animal model of CHI, carotid arteries were ligatured and then cut bilaterally. To evaluation of passive avoidance memory, step-down latency (STL was measured and LTP was recorded from hippocampal dentate gyrus (DG after high frequency stimulation (HFS in all rats. Results: We found that memory was significantly impaired in rats after CHI (P

  20. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Science.gov (United States)

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  1. Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats.

    Science.gov (United States)

    Bellaver, Bruna; Souza, Débora Guerini; Souza, Diogo Onofre; Quincozes-Santos, André

    2014-06-01

    Astrocytes are responsible for modulating neurotransmitter systems and synaptic information processing, ionic homeostasis, energy metabolism, maintenance of the blood-brain barrier, and antioxidant and inflammatory responses. Our group recently published a culture model of cortical astrocytes obtained from adult Wistar rats. In this study, we established an in vitro model for hippocampal astrocyte cultures from adult (90 days old) and aged (180 days old) Wistar rats. Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant, anti-inflammatory, anti-aging and neuroprotective effects that modulate glial functions. Here, we evaluated the effects of resveratrol on GSH content, GS activity, TNF-α and IL-1β levels in hippocampal astrocytes from newborn, adult and aged Wistar rats. We observed a decrease in antioxidant defenses and an increase in the inflammatory response in hippocampal astrocytes from adult and aged rats compared to classical astrocyte cultures from newborn rats. Resveratrol prevented these effects. These findings reinforce the neuroprotective effects of resveratrol, which are mainly associated with antioxidant and anti-inflammatory activities.

  2. Kindling induces transient fast inhibition in the dentate gyrus--CA3 projection.

    Science.gov (United States)

    Gutiérrez, R; Heinemann, U

    2001-04-01

    The granule cells of the dentate gyrus (DG) send a strong glutamatergic projection, the mossy fibre tract, toward the hippocampal CA3 field, where it excites pyramidal cells and neighbouring inhibitory interneurons. Despite their excitatory nature, granule cells contain small amounts of GAD (glutamate decarboxylase), the main synthetic enzyme for the inhibitory transmitter GABA. Chronic temporal lobe epilepsy results in transient upregulation of GAD and GABA in granule cells, giving rise to the speculation that following overexcitation, mossy fibres exert an inhibitory effect by release of GABA. We therefore stimulated the DG and recorded synaptic potentials from CA3 pyramidal cells in brain slices from kindled and control rats. In both preparations, DG stimulation caused excitatory postsynaptic potential (EPSP)/inhibitory postsynaptic potential (IPSP) sequences. These potentials could be completely blocked by glutamate receptor antagonists in control rats, while in the kindled rats, a bicuculline-sensitive fast IPSP remained, with an onset latency similar to that of the control EPSP. Interestingly, this IPSP disappeared 1 month after the last seizure. When synaptic responses were evoked by high-frequency stimulation, EPSPs in normal rats readily summate to evoke action potentials. In slices from kindled rats, a summation of IPSPs overrides that of the EPSPs and reduces the probability of evoking action potentials. Our data show for the first time that kindling induces functionally relevant activity-dependent expression of fast inhibition onto pyramidal cells, coming from the DG, that can limit CA3 excitation in a frequency-dependent manner.

  3. Hepatotrophic activity of benzodiazepine drugs in adult rats of either sex.

    Science.gov (United States)

    Gershbein, L L

    1994-07-01

    Adult rats with two-thirds of the liver removed were administered diets supplemented with benzodiazepine drugs over a period of 10 days and the mass of organ regenerated or the liver increment ascertained. For a number of the drugs, liver regeneration was stimulated; the effect was more consistent and reproducible in the adult female. On the basis of the lower sensitivity of the male, such animals provided an approach toward rating the hepatotrophic efficacy of the agents and in relation to structure. According to the current classification, hepatotrophic activity was higher with lorazepam, loprazolam, oxazepam and chlordiazepoxide; intermediate with nitrazepam, temazepam, quazepam, halazepam and triazepam and lower with diazepam, clorazepate dipotassium, clobazam and alprazolam. More reproducible responses in terms of g wet and dry liver per 100 g body weight were obtained with sham-operated or intact males. The antagonist, flumazenil, fed at 0.080% was not effective as such nor modified the responses in admixture with several drugs in partially hepatectomized or intact males. In vivo hepatic microsomal changes in protein, cytochrome P-450 or the enzymes, aminopyrine demethylase and benzo[a]pyrene hydroxylase with the various series were not remarkable or sporadic. Among other factors, the liver incremental changes noted currently are dependent on the metabolic intermediate benzodiazepines of varying elimination half-lives which may be distinct from that of the parent drug coupled with the alterations induced by partial ablation of the organ in rats of either sex.

  4. Stem cells in the adult rat spinal cord: plasticity after injury and treadmill training exercise.

    Science.gov (United States)

    Foret, Ariane; Quertainmont, Renaud; Botman, Olivier; Bouhy, Delphine; Amabili, Philippe; Brook, Gary; Schoenen, Jean; Franzen, Rachelle

    2010-02-01

    Ependymal cells located around the central canal of the adult spinal cord are considered as a source of neural stem cells (NSCs) and represent an interesting pool of endogenous stem cells for repair strategies. Physical exercise is known to increase ependymal cell proliferation, while improving functional recovery. In this work, we further characterized those endogenous NSCs within the normal and injured adult rat spinal cord and investigated the effects of treadmill training using immunohistochemical and behavioral studies. In uninjured untrained rats, Sox-2, a NSC marker, was detected in all ependymal cells of the central canal, and also scattered throughout the parenchyma of the spinal cord. Within the lesion, Sox-2 expression increased transiently, while the number of nestin-positive ependymal cells increased with a concomitant enhancement of proliferation, as indicated by the mitotic markers Ki67 and bromo-deoxyuridine. Exercise, which improved functional recovery and autonomous micturition, maintained nestin expression in both injured and uninjured spinal cords, with a positive correlation between locomotor recovery and the number of nestin-positive cells.

  5. Cortical neurogenesis in adult rats after ischemic brain injury:most new neurons fail to mature

    Institute of Scientific and Technical Information of China (English)

    Qing-quan Li; Guan-qun Qiao; Jun Ma; Hong-wei Fan; Ying-bin Li

    2015-01-01

    The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial ifbrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identiifed using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromode-oxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial ifbrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our ifndings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  6. Subacute toxicity assessment of diflubenzuron, an insect growth regulator, in adult male rats.

    Science.gov (United States)

    de Barros, Aline Lima; Cavalheiro, Gabriela Finoto; de Souza, Alexsandra Vila Maior; Traesel, Giseli Karenina; Anselmo-Franci, Janete A; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

    2016-04-01

    Diflubenzuron (DFB), an insecticide and acaricide insect growth regulator, can be used in agriculture against insect predators and in public health programs, to control insects and vectors, mainly Aedes aegypti larvae. Due to the lack of toxicological assessments of this compound, the objective of the present study was to evaluate the toxicological effects of subacute exposure to the DFB insecticide in adult male rats. Adult male rats were exposed (gavage) to 0, 2, 4, or 8 mg/kg of DFB for 28 days. No clinical signs of toxicity were observed in the DFB-treated animals of the experimental groups. However, there was an increase in serum levels of alanine aminotransferase in the group that received 8 mg/kg/DFB/day and urea at doses of 4 and 8 mg/kg/DFB/day, without altering other biochemical or hematological parameters. The subacute exposure to the lowest dose of DFB caused significant decrease in testis weight, daily sperm production, and in number of sperm in the epididymis in relation to the control group. However, no alterations were observed in the sperm morphology, testicular, epididymis, liver and kidney histology, or testosterone levels. These findings unveiled the hazardous effects of DFB on male reproduction after the subacute exposure and special attention should be addressed to the effects of low doses of this pesticide.

  7. Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

    Directory of Open Access Journals (Sweden)

    Jodi L. Pawluski

    2014-01-01

    Full Text Available Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1 cookie and (2 osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat.

  8. Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior.

    Science.gov (United States)

    Takada, Silvia Honda; Motta-Teixeira, Lívia Clemente; Machado-Nils, Aline Vilar; Lee, Vitor Yonamine; Sampaio, Carlos Alberto; Polli, Roberson Saraiva; Malheiros, Jackeline Moraes; Takase, Luiz Fernando; Kihara, Alexandre Hiroaki; Covolan, Luciene; Xavier, Gilberto Fernando; Nogueira, Maria Inês

    2016-01-01

    Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches.

  9. Renoprotective effects of moringa oleifera leaf extract on the kidneys of adult wistar rats

    Directory of Open Access Journals (Sweden)

    Ezejindu D. N

    2016-07-01

    Full Text Available Moringa oleifera is one of several nutritional supplements giving wide spread popularity in Nigeria and many other countries of the world. The leaves and flowers are being used by the population with great dietary importance. The aim of this study is to investigate the effects of oral administration of Moringa oleifera leaf extract on the kidneys of adult wistar rats. 24 apparently healthy adult wistar rats weighing between190- 230kg were divided into four groups of six animals each. Group A served as the control and received 0.3ml of distilled water orally. The experimental groups B, C & D received 0.5ml, 0.6ml &0.7ml of Moringa oleifera extract orally respectively. The administration lasted for twenty one days. The animals were weighed, sacrificed using chloroform vapour. The kidney tissue were removed, weighed and trimmed down for histological studies. Result of this study showed non-distortion of the kidney cells. The findings of this study suggest that chronic Moringa oleifera consumption may not put the kidneys at risk of adverse histopathological conditions.

  10. Bisphenol A exposure at an environmentally relevant dose induces meiotic abnormalities in adult male rats.

    Science.gov (United States)

    Liu, Chuan; Duan, Weixia; Zhang, Lei; Xu, Shangcheng; Li, Renyan; Chen, Chunhai; He, Mindi; Lu, Yonghui; Wu, Hongjuan; Yu, Zhengping; Zhou, Zhou

    2014-01-01

    Whether environmental exposure to bisphenol A (BPA) may induce reproductive disorders is still controversial but certain studies have reported that BPA may cause meiotic abnormalities in C. elegans and female mice. However, little is known about the effect of BPA on meiosis in adult males. To determine whether BPA exposure at an environmentally relevant dose could induce meiotic abnormalities in adult male rats, we exposed 9-week-old male Wistar rats to BPA by gavage at 20 μg/kg body weight (bw)/day for 60 consecutive days. We found that BPA significantly increased the proportion of stage VII seminiferous epithelium and decreased the proportion of stage VIII. Consequently, spermiation was inhibited and spermatogenesis was disrupted. Further investigation revealed that BPA exposure delayed meiosis initiation in the early meiotic stage and induced the accumulation of chromosomal abnormalities and meiotic DNA double-strand breaks (DSBs) in the late meiotic stage. The latter event subsequently activated the phosphatidylinositol 3-kinase-related protein kinase (ATM). Our results suggest that long-term exposure to BPA may lead to continuous meiotic abnormalities and ultimately put mammalian reproductive health at risk.

  11. Effects of Extremely Low Frequency Electromagnetic Fields on Vascular Permeability of Circumventricular Organs in the Adult Rat

    Science.gov (United States)

    Gutiérrez-Mercado, Y. K.; Cañedo-Dorantes, L.; Bañuelos-Pineda, J.; Serrano-Luna, G.; Feria-Velasco, A.

    2008-08-01

    The present work deals with the effects of extremely low frequency electromagnetic fields (ELF-EMF) on blood vessels permeability to non liposoluble substances of the circumventricular organs (CVO) of adult rats. Male Wistar adult rats were exposed to ELF-EMF and vascular permeability to colloidal carbon was investigated with the use of histological techniques. Results were compared to corresponding data from sham-exposed and control groups of animals. Exposure to ELF-EMF increased the CVO vascular permeability to colloidal carbon intravascularly injected, particularly in the subfornical organ, the median eminence, the pineal gland and the area postrema.

  12. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Guizar-Sahagun, G. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Inst. Mexicano del Seguro Social, Mexico City (Mexico)); Rivera, F. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico)); Babinski, E. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico)); Berlanga, E. (Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico)); Madrazo, M. (Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico)); Franco-Bourland, R. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Biochemistry, Inst. Nacional de la Nutricion, Mexico City (Mexico)); Grijalva, I. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo

    1994-08-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  13. PROLIFERATION AND DIFFERENTIATION OF NEURAL STEM CELLS IN ADULT RATS AFTER CEREBRAL INFARCTION

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Ren-zhi Wang; Yong Yao; Zhi-hai Liu; Zhi-gang Lian; Yu-jie Zou; Yu-kui Wei

    2004-01-01

    Objective To investigate proliferation and differentiation of neural stem cells in adult rats after cerebral infarction.Methods Models of cerebral infarction in rats were made and the time-course expression of bromodeoxyuridine (BrdU), Musashil, glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU and Musashil were used to mark dividing neural stem cells. GFAP and NeuN were used to mark differentiating neural stem cells.Results Compared with controls, the number of BrdU-labeled and BrdU-labeled with Musashil-positive cells increased strikingly 1 day after cerebral infarction; approximately 6 fold with a peak 7 days later; markedly decreased 14 days later, but was still elevated compared with that of controls; decling to the control level 28 days later. The number of BrdU-labeled with GFAP-positive cells nearly remained unchanged in the hippocampus after cerebral infarction. The number of BrdU-labeled with NeuN-positive cells increased strikingly 14 days after cerebral infarction, reached maximum peak in the hippocampus 28 days after cerebral infarction in rats.Conclusion Cerebral infarction stimulate proliferation of inherent neural stem cells and most proliferated neural stem cells differentiate into neurons.

  14. Adrenal steroidogenesis disruption caused by HDL/cholesterol suppression in diethylstilbestrol-treated adult male rat.

    Science.gov (United States)

    Haeno, Satoko; Maeda, Naoyuki; Yamaguchi, Kousuke; Sato, Michiko; Uto, Aika; Yokota, Hiroshi

    2016-04-01

    The synthetic estrogen diethylstilbestrol is used to prevent miscarriages and as a therapeutic treatment for prostate cancer, but it has been reported to have adverse effects on endocrine homeostasis. However, the toxicity mechanism is poorly understood. Recently, we reported that diethylstilbestrol impairs adrenal steroidogenesis via cholesterol insufficiency in adult male rats. In the present study, we found that the adrenal cholesterol level was significantly reduced without of the decrease in other precursors in the adrenal steroidogenesis 24 h after a single dose of diethylstilbestrol (0.33 μg/g body mass). The serum HDL/cholesterol level was also reduced only 12 h after the diethylstilbestrol exposure. The level of Apo E, which is indispensable for HDL/cholesterol maturation, was decreased in both the HDL and VLDL/LDL fractions, whereas the level of Apo A1, which is an essential constituent of HDL, was not altered in the HDL fraction. Because the liver is a major source of Apo E and Apo A1, the secretion rates of these proteins were examined using a liver perfusion experiment. The secretion rate of Apo A1 from the liver was consistent between DES-treated and control rats, but that of Apo E was comparatively suppressed in the DES-treated rats. The disruption of adrenal steroidogenesis by diethylstilbestrol was caused by a decrease in serum HDL/cholesterol, which is the main source of adrenal steroidogenesis, due to the inhibition of Apo E secretion from the liver.

  15. Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats.

    Science.gov (United States)

    Fuentes, Silvia; Carrasco, Javier; Armario, Antonio; Nadal, Roser

    2014-08-01

    Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23-28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors.

  16. Effects of morphine on thermal sensitivity in adult and aged rats.

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    Morgan, Drake; Mitzelfelt, Jeremiah D; Koerper, Lorraine M; Carter, Christy S

    2012-06-01

    There are contradictory data regarding older individuals' sensitivity to pain stimulation and opioid administration. Adult (12-16 months; n = 10) and aged (27-31 months; n = 7) male F344xBN rats were tested in a thermal sensitivity procedure where the animal chooses to remain in one of two compartments with floors maintained at various temperatures ranging from hot (45°C) through neutral (30°C) to cold (15°C). Effects of morphine were determined for three temperature comparisons (ie, hot/neutral, cold/neutral, and hot/cold). Aged rats were more sensitive to cold stimulation during baseline. Morphine produced antinociception during hot thermal stimulation, but had no effect on cold stimulation. The antinociceptive (and locomotor-altering) effects of morphine were attenuated in aged rats. These data demonstrate age-related differences in baseline thermal sensitivity and responsiveness to opioids. Based on behavioral and physiological requirements of this procedure, it is suggested that thermal sensitivity may provide a relevant animal model for the assessment of pain and antinociception.

  17. Neonatal local noxious insult affects gene expression in the spinal dorsal horn of adult rats

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    Dubner Ronald

    2005-09-01

    Full Text Available Abstract Neonatal noxious insult produces a long-term effect on pain processing in adults. Rats subjected to carrageenan (CAR injection in one hindpaw within the sensitive period develop bilateral hypoalgesia as adults. In the same rats, inflammation of the hindpaw, which was the site of the neonatal injury, induces a localized enhanced hyperalgesia limited to this paw. To gain an insight into the long-term molecular changes involved in the above-described long-term nociceptive effects of neonatal noxious insult at the spinal level, we performed DNA microarray analysis (using microarrays containing oligo-probes for 205 genes encoding receptors and transporters for glutamate, GABA, and amine neurotransmitters, precursors and receptors for neuropeptides, and neurotrophins, cytokines and their receptors to compare gene expression profiles in the lumbar spinal dorsal horn (LDH of adult (P60 male rats that received neonatal CAR treatment within (at postnatal day 3; P3 and outside (at postnatal 12; P12 of the sensitive period. The data were obtained both without inflammation (at baseline and during complete Freund's adjuvant induced inflammation of the neonatally injured paw. The observed changes were verified by real-time RT-PCR. This study revealed significant basal and inflammation-associated aberrations in the expression of multiple genes in the LDH of adult animals receiving CAR injection at P3 as compared to their expression levels in the LDH of animals receiving either no injections or CAR injection at P12. In particular, at baseline, twelve genes (representing GABA, serotonin, adenosine, neuropeptide Y, cholecystokinin, opioid, tachykinin and interleukin systems were up-regulated in the bilateral LDH of the former animals. The baseline condition in these animals was also characterized by up-regulation of seven genes (encoding members of GABA, cholecystokinin, histamine, serotonin, and neurotensin systems in the LDH ipsilateral to the

  18. Neonatal local noxious insult affects gene expression in the spinal dorsal horn of adult rats.

    Science.gov (United States)

    Ren, Ke; Novikova, Svetlana I; He, Fang; Dubner, Ronald; Lidow, Michael S

    2005-09-22

    Neonatal noxious insult produces a long-term effect on pain processing in adults. Rats subjected to carrageenan (CAR) injection in one hindpaw within the sensitive period develop bilateral hypoalgesia as adults. In the same rats, inflammation of the hindpaw, which was the site of the neonatal injury, induces a localized enhanced hyperalgesia limited to this paw. To gain an insight into the long-term molecular changes involved in the above-described long-term nociceptive effects of neonatal noxious insult at the spinal level, we performed DNA microarray analysis (using microarrays containing oligo-probes for 205 genes encoding receptors and transporters for glutamate, GABA, and amine neurotransmitters, precursors and receptors for neuropeptides, and neurotrophins, cytokines and their receptors) to compare gene expression profiles in the lumbar spinal dorsal horn (LDH) of adult (P60) male rats that received neonatal CAR treatment within (at postnatal day 3; P3) and outside (at postnatal 12; P12) of the sensitive period. The data were obtained both without inflammation (at baseline) and during complete Freund's adjuvant induced inflammation of the neonatally injured paw. The observed changes were verified by real-time RT-PCR. This study revealed significant basal and inflammation-associated aberrations in the expression of multiple genes in the LDH of adult animals receiving CAR injection at P3 as compared to their expression levels in the LDH of animals receiving either no injections or CAR injection at P12. In particular, at baseline, twelve genes (representing GABA, serotonin, adenosine, neuropeptide Y, cholecystokinin, opioid, tachykinin and interleukin systems) were up-regulated in the bilateral LDH of the former animals. The baseline condition in these animals was also characterized by up-regulation of seven genes (encoding members of GABA, cholecystokinin, histamine, serotonin, and neurotensin systems) in the LDH ipsilateral to the neonatally-injured paw. The

  19. Perinatal Nicotine Exposure Increases Obesity Susceptibility in Adult Male Rat Offspring by Altering Early Adipogenesis.

    Science.gov (United States)

    Fan, Jie; Zhang, Wan-Xia; Rao, Yi-Song; Xue, Jing-Ling; Wang, Fei-Fei; Zhang, Li; Yan, You-E

    2016-11-01

    The present study aims to evaluate whether perinatal nicotine (NIC) exposure increases obesity susceptibility in adult male rat offspring by altering early adipogenesis. NIC was sc administered (2.0 mg/kg per day) to pregnant rats from gestational day 9 to the time of weaning (postnatal day 28). At weaning, NIC-exposed male pups had an increased body weight and inguinal sc fat mass and a decreased average cell area of adipocyte, which was accompanied by an overexpression of adipogenic and lipogenic genes in the epididymal white adipose tissue. Additionally, the hepatic lipogenic gene levels from NIC-exposed male pups were also affected. At 12 and 26 weeks of age, body weight and fat mass were increased, whereas there was no change in food intake in NIC-exposed male offspring. Adipogenic and lipogenic genes, glucose transporter 4, and leptin mRNA levels were increased, whereas adiponectin mRNA levels were decreased in the epididymal white adipose tissue of NIC-exposed males. The hepatic lipogenic gene expression of NIC-exposed males was increased. NIC-exposed male offspring showed normal glycemia and a higher serum insulin level, homeostasis model assessment of insulin resistance, and homeostasis model assessment of β-cell function. Furthermore, the NIC-exposed male offspring showed higher serum lipids and Castelli index I and lower nonesterified fatty acid. At 26 weeks, in the ip glucose and insulin tolerance tests, the glucose clearance was delayed, and the area under the curve was higher in the NIC-exposed male offspring. In conclusion, perinatal NIC exposure increased obesity susceptibility in adult male rat offspring by altering early adipogenesis.

  20. Subculture of proliferating adult rat hepatocytes in medium supplemented with nicotinamide and EGF.

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    Mitaka, T; Kojima, T; Mizuguchi, T; Mochizuki, Y

    1996-09-01

    To establish parenchymal hepatocyte cell lines, we tried to subculture the primary hepatocytes isolated from adult rats. The hepatocytes were cultured in serum-free modified Dulbecco's modified Eagle's medium supplemented with 10 mM nicotinamide and 10 ng/ml epidermal growth factor. When 6 x 10(5) cells were plated on 35-mm dishes coated with rat tail collagen, the cells proliferated and reached confluence at Day 6 to Day 8. The first subculture was carried out at Day 8 using 0.005% collagenase and gentle pipettings. Most cells were recovered and plated on the new dishes coated with the collagen (first passage). The attached cells could proliferate and reached near confluence when the cells occupied more than two-thirds of the dish surface. About a week after the first subculture, the second one was conducted. Although the number of the recovered cells was smaller than at the first passage, the cells could attach and proliferate to a certain extent. Thereafter, they were maintained for more than 2 mo, but they never overgrew. Albumin secretion into the culture medium was confirmed in the subcultured cells. Ultrastructurally, these subcultured cells possessed hepatic characteristics such as peroxisomes with a crystalline nucleiod and bile-canaliculus structures. When 10% fetal bovine serum and ascorbic acid 2-phosphate were added to the cells of the second passage, they began to proliferate very slowly. These proliferating cells were mainly mononucleate and had a small cytoplasm. In addition, some of them could differentitate into typical mature hepatocytes by forming a three-dimensional structure interacting with nonparenchymal cells. In this experiment, we showed the successful subculturing of parenchymal hepatocytes isolated from adult rats and provided evidence that the subcultured cells still have the potential to proliferate and to differentiate.

  1. The Histopathological Effect of Sildenafil Citrate on Superior Colliculus of Adult Male Rat

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    Amany Shams

    2013-08-01

    Full Text Available Objective: Preclinical and very limited clinical studies suggest that sildenafil may have therapeutic potential in selected neurological disorders. However, many neurological side effects of sildenafil have been reported. This work aimed to clarify the histopathological effect of sildenafil citrate on the superior colliculus (SC of adult male albino rat. Material and methods: 24 adult male albino rats were used and divided into 4 groups. The first 3 groups were received respectively sildenafil citrate orally at doses 0.25, 0.70 and 1.43mg/kg body weight daily for 30 days while the 4th group was used as control. At end of the treatment, the superior colliculi were undergone light and electron microscopic investigation. Results: In the control group, superficial part of the SC has neural cells and myelinated nerve fibers. With least dose of sildenafil, the superficial part of SC revealed disturbance in neural tissue with dilated capillaries and vacuoles. Some neurons showed deeply stained nuclei shrunken cytoplasm. Some cells showed enlarged mitochondria and dilated endoplasmic reticulum. With medium dose of sildenafil, SC showed more disturbances; stripped myelin sheaths or widely separated myelin lamellae, dilated blood vessels with large vacuoles around them and many neurons with apoptotic criteria. However, maximum dose of sildenafil induced massive destruction of edematous neural tissue; invasion of the surface with massive blood vessels, marked decrease in thickness of myelin sheaths and the neural cells revealed degenerative and apoptotic changes. The mean number and size of cells revealed significantly progressive decrease in all treated rats with increasing doses of the drug. Conclusion: Long-term, daily use of sildenafil can lead to pathological effect in the superior colliculus which may be implicated in visual disturbance and this effect is dose dependent, so neurological effect of sildenafil necessitates further investigations. [J

  2. Identification of interneurons activated at different inclines during treadmill locomotion in adult rats.

    Science.gov (United States)

    Tillakaratne, Niranjala J K; Duru, Paul; Fujino, Hidemi; Zhong, Hui; Xiao, Mei Si; Edgerton, V Reggie; Roy, Roland R

    2014-12-01

    By using c-fos as an activity-dependent marker, we identified the cholinergic interneurons around the central canal and lumbar interneurons throughout the gray matter that were activated after a 30-min bout of quadrupedal treadmill stepping at a 0° or 25° incline in adult rats. Increased loading (elevated treadmill incline) imposed during treadmill stepping activated more cholinergic interneurons in the proximity of the central canal, i.e., central canal cluster cells and partition neurons. Since cholinergic central canal cells are thought to modulate motoneuron excitability, these data suggest that increased load during stepping may increase motoneuronal activity through activating more cholinergic central canal cells. We identified the muscle-specific motoneurons and afferent terminals in the spinal cord by injecting cholera toxin subunit B in the soleus and tibialis anterior muscles. The number of interneurons in lumbar segments L4 (tibialis anterior) and L5 (soleus) was higher in both groups that stepped on the treadmill compared with control and was highest in rats that stepped at a 25° incline. In a majority of laminae, the distribution of total and muscle-specific activated interneurons was highest in the 25° incline group and lowest in the control group for both muscles. These data could reflect increased peripheral (proprioceptive) input as well as supraspinal drive associated with stepping and demonstrate the differences in 1) the activation of cholinergic interneurons near the central canal and 2) the laminar and segmental location of interneurons throughout the gray matter that play a role in generating stepping under different loading conditions in adult rats.

  3. Effects of H2S on the central regulation of respiration in adult rats.

    Science.gov (United States)

    Li, Hui; Hou, Xuefei; Ding, Yan; Nie, Lihong; Zhou, Hua; Nie, Zheng; Tang, Yuhong; Chen, Li; Zheng, Yu

    2014-04-16

    Hydrogen sulfide (H2S) is a gasotransmitter synthesized from cysteine (Cys) by pyridoxal-5'-phosphate-dependent enzymes. We investigated the potential roles of H2S in the regulation of central rhythmic respiration in adult rats in vivo. Sodium hydrosulfide (NaHS: 2.5 mM, 10 mM, and 5 mM) as a source of exogenous H2S, Cys (2.5 mM, 10 mM and 5 mM) as a source of endogenous H2S, 2.5 mM Cys+10 mM hydroxylamine (NH2OH), and 10 mM NH2OH, respectively, were intracerebroventricularly injected into rats. The rhythmic discharge of the diaphragm, including burst duration (BD), burst interval (BI), burst frequency (BF), and integrated amplitude (IA), and arterial blood pressure (BP) were measured at different time points. The results were analyzed by analysis of variance. A total of 2.5 mM NaHS did not significantly affect changes in BD, BI, BF, IA, or BP (P>0.05), whereas 2.5 mM Cys significantly altered BD, BI, and BF (P0.05). A concentration of 5 mM Cys had effects similar to those of 5 mM NaHS; both induced biphasic respiratory responses and changed the BF (P0.05) except for BD was temporarily decreased (P<0.05) in the 2.5 mM Cys+10 mM NH2OH group. These results suggest that exogenous and endogenous H2S may participate in the regulation of respiratory activity in adult rats.

  4. The effect of Jujuboside A on the evoked field potentials of granule cells in dentate gyrus

    Institute of Scientific and Technical Information of China (English)

    封洲燕; 郑筱祥

    2002-01-01

    Jujuboside A (JuA) is a main component of Jujubogenin extracted from the seeds of Ziziphus. The authors have not seen any report on JuA's direct effect on the neurons of the central nervous system. This study aimed to assess the effect of JuA on paired-pulse responses of dentate gyrus granule cells in urethane-anaesthetized rats, used intracerebroventricular (i.c.v.) JuA to mimic in vitro bath conditions in vivo. Paired-pulse stimuli with 80ms interpulse interval were used to stimulate the perforant pathway. Evoked responses were recorded in the dentate gyrus cell layer after i.c.v. administration of 0.9% normal saline or JuA. In the first responses, the slopes of excitatory postsynaptic potential (EPSP1) and the amplitudes of population spike (PS1) decreased significantly after administration of JuA while the PS1 latencies increased significantly. In the second responses, the EPSP2 slopes and PS2 latencies were changed similarly to those of the first ones, but PS2 amplitudes increased. The results showed that JuA may have some inhibitory effect on the granule cell excitability mediated by presynaptic mechanism but may have little effect on the excitability mediated by postsynaptic mechanism since the second evoked N-methyl-D-aspartic mediating paired-pulse facilitation is a postsynaptic mechanism.

  5. HISTOLOGICAL STUDIES OF THE EFFECTS OF MONOSODIUM GLUTAMATE ON THE MEDIAL GENICULATE BODY OF ADULT WISTAR RATS

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    A.O.Eweka

    2007-01-01

    Full Text Available Histological effects of Monosodium glutamate (MSG commonly used as food additive on the medial geniculate body (MGB of adult wistar rats were carefully studied. The rats of both sexes (n=24, average weight of 185g were randomly assigned into two treatments (n=16 and control (n=8 groups.The rats in the treatment groups received 3g and 6g of MSG thoroughly mixed with their feeds for fourteen days, while the control rats received equal amounts of feeds without MSG added. The rats were fed with grower's mash purchased from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The medial geniculate body was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method.The histological findings after H&E methods indicated that the treated sections of the medial geniculate body showed some cellular degenerative changes, autophagic vacuoles with some vacuolations appearing in the stroma, and some degree of neuronal hypertrophy when compared to the control sections. These findings indicate that MSG consumption may have a deleterious effect on the neurons of the medial geniculate body (MGB. MSG may probably have adverse effects on the auditory sensibilities by its deleterious effects on the nerve cells of the MGB of adult wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

  6. Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring.

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    Care, Alison S; Sung, Miranda M; Panahi, Sareh; Gragasin, Ferrante S; Dyck, Jason R B; Davidge, Sandra T; Bourque, Stephane L

    2016-05-01

    This study was undertaken to determine whether perinatal maternal resveratrol (Resv)--a phytoalexin known to confer cardiovascular protection--could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (-18 mm Hg; P=0.007), and nitric oxide synthase inhibition (with L-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment with L-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric arteries was reduced in Resv-treated offspring (-28%; Phypertension and causes persistent alterations in vascular responsiveness in spontaneously hypertensive rats.

  7. Development of the glucocorticoid receptor system in the rat limbic brain. 2. An autoradiographic study

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    Meaney, M.J.; Sapolsky, R.M.; McEwen, B.S. (Rockefeller Univ., New York (USA))

    1985-02-01

    The authors report the results of an autoradiographic analysis of the postnatal development of the hippocampal glucocorticoid receptor system in the rat brain. Quantitative analysis of the autoradiograms revealed a varied pattern of gradual development towards adult receptor concentrations during the second week of life. Receptor concentrations in the dentate gyrus increased dramatically between Days 9 and 15, while the changes during this period in the pyramidal layers of Ammon's horn seemed to reflect both structural changes in these regions as well as increases in receptor concentrations.

  8. Characterization and enrichment of hepatic progenitor cells in adult rat liver

    Institute of Scientific and Technical Information of China (English)

    Ai-Lan Qin; Xia-Qiu Zhou; Wei Zhang; Hong Yu; Qin Xie

    2004-01-01

    AIM: To detect the markers of oval cells in adult rat liver and to enrich them for further analysis of characterization in vitro.METHODS: Rat model for hepatic oval cell proliferation was established with 2-acetylaminofluorene and two third partial hepatectomy (2-AAF/PH). Paraffin embedded rat liver sections from model (11 d after hepatectomy) and control groups were stained with HE and OV6, cytokeratin19 (CK19),albumin, alpha fetoprotein (AFP), connexin43, and c-kit antibodies by immunohistochemistry. Oval cell proliferation was measured with BrdU incorporation test. C-kit positive oval cells were enriched by using magnetic activated cell sorting (MACS) .The sorted oval cells were cultured in a low density to observe colony formation and to examine their characterization in vitroby immunocytochemistry and RT-PCR. RESULTS: A 2-AAF/PH model was successfully established to activate the oval cell compartment in rat liver. BrdU incorporation test of oval cell was positive. The hepatic oval cells coexpressed oval cell specific marker OV6, hepatocytemarker albumin and cholangiocyte-marker CK19. They also expressed AFP and connexin 43. C-kit, one hematopoietic stem cell receptor, was expressed in hepatic oval cells at high levels. By using c-kit antibody in conjunction with MACS,we developed a rapid oval cell isolation protocol. The sorted cells formed colony when cultured in vitro. Cells in the colony expressed albumin or CK19 or coexpressed both and BrdU incorporation test was positive. RT-PCR on colony showed expression of albumin and CK19 gene.CONCLUSION: Hepatic oval cells in the 2-AAF/PH model had the properties of hepatic stem/progenitor cells. Using MACS, we established a method to isolate oval cells. The sorted hepatic oval cells can form colony in vitro which expresses different combinations of phenotypic markers and genes from both hepatocytes and cholangiocyte lineage.

  9. AVPV neurons containing estrogen receptor-beta in adult male rats are influenced by soy isoflavones

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    Bu Lihong

    2007-02-01

    Full Text Available Abstract Background Isoflavones, the most abundant phytoestrogens in soy foods, are structurally similar to 17beta-estradiol. It is known that 17beta-estradiol induces apoptosis in anteroventral periventricular nucleus (AVPV in rat brain. Also, there is evidence that consumption of soy isoflavones reduces the volume of AVPV in male rats. Therefore, in this study, we examined the influence of dietary soy isoflavones on apoptosis in AVPV of 150 day-old male rats fed either a soy isoflavone-free diet (Phyto-free or a soy isoflavone-rich diet (Phyto-600. Results The occurrence of apoptosis in AVPV was examined by TUNEL staining. The incidence of apoptosis was about 10 times higher in the Phyto-600 group (33.1 ± 1.7% than in the Phyto-free group (3.6 ± 1.0%. Furthermore, these apoptotic cells were identified as neurons by dual immunofluorescent staining of GFAP and NeuN as markers of astrocytes and neurons, respectively. Then the dopaminergic neurons in AVPV were detected by immunohistochemistry staining of tyrosine hydroxylase (TH. No significant difference in the number of TH neurons was observed between the diet treatment groups. When estrogen receptor (ER alpha and beta were examined by immunohistochemistry, we observed a 22% reduction of ERbeta-positive cell numbers in AVPV with consumption of soy isoflavones, whereas no significant change in ERalpha-positive cell numbers was detected. Furthermore, almost all the apoptotic cells were ERbeta-immunoreactive (ir, but not ERalpha-ir. Last, subcutaneous injections of equol (a major isoflavone metabolite that accounts for approximately 70–90% of the total circulating plasma isoflavone levels did not alter the volume of AVPV in adult male rats. Conclusion In summary, these findings provide direct evidence that consumption of soy isoflavones, but not the exposure to equol, influences the loss of ERbeta-containing neurons in male AVPV.

  10. The effects of biological sex and gonadal hormones on learning strategy in adult rats.

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    Hawley, Wayne R; Grissom, Elin M; Barratt, Harriet E; Conrad, Taylor S; Dohanich, Gary P

    2012-02-28

    When learning to navigate toward a goal in a spatial environment, rodents employ distinct learning strategies that are governed by specific regions of the brain. In the early stages of learning, adult male rats prefer a hippocampus-dependent place strategy over a striatum-dependent response strategy. Alternatively, female rats exhibit a preference for a place strategy only when circulating levels of estradiol are elevated. Notably, male rodents typically perform better than females on a variety of spatial learning tasks, which are mediated by the hippocampus. However, limited research has been done to determine if the previously reported male spatial advantage corresponds with a greater reliance on a place strategy, and, if the male preference for a place strategy is impacted by removal of testicular hormones. A dual-solution water T-maze task, which can be solved by adopting either a place or a response strategy, was employed to determine the effects of biological sex and hormonal status on learning strategy. In the first experiment, male rats made more correct arm choices than female rats during training and exhibited a bias for a place strategy on a probe trial. The results of the second experiment indicated that testicular hormones modulated arm choice accuracy during training, but not the preference for a place strategy. Together, these findings suggest that the previously reported male spatial advantage is associated with a greater reliance on a place strategy, and that only performance during the training phase of a dual-solution learning task is impacted by removal of testicular hormones.

  11. Neonatal Androgen Exposure Causes Persistent Gut Microbiota Dysbiosis Related to Metabolic Disease in Adult Female Rats.

    Science.gov (United States)

    Moreno-Indias, Isabel; Sánchez-Alcoholado, Lidia; Sánchez-Garrido, Miguel Ángel; Martín-Núñez, Gracia María; Pérez-Jiménez, Francisco; Tena-Sempere, Manuel; Tinahones, Francisco J; Queipo-Ortuño, María Isabel

    2016-12-01

    Alterations of gut microbiome have been proposed to play a role in metabolic disease, but the major determinants of microbiota composition remain ill defined. Nutritional and sex hormone challenges, especially during early development, have been shown to permanently alter adult female phenotype and contribute to metabolic disturbances. In this study, we implemented large-scale microbiome analyses to fecal samples from groups of female rats sequentially subjected to various obesogenic manipulations, including sex hormone perturbations by means of neonatal androgenization or adult ovariectomy (OVX), as a model of menopause, to establish whether these phenomena are related to changes in gut microbiota. Basic metabolic profiles concerning glucose/insulin homeostasis were also explored. The effects of the sex hormonal perturbations, either developmentally (androgenization) or in adulthood (OVX), clearly outshone the impact of nutritional interventions, especially concerning the gut microbiota profile. Notably, we observed a lower diversity in the androgenized group, with the highest Firmicutes to Bacteroidetes ratio, supporting the occurrence of durable alterations in gut microbiota composition, even in adulthood. Moreover, the elimination of adult ovarian secretions by OVX affected the richness of gut microbiota. Our data are the first to document the durable impact of sex steroid manipulations, and particularly early androgenization, on gut microbiota composition. Such dysbiosis is likely to contribute to the metabolic perturbations of conditions of obesity linked to gonadal dysfunction in the female.

  12. Persistent sodium current properties in hippocampal CA1 pyramidal neurons of young and adult rats.

    Science.gov (United States)

    Lunko, Oleksii; Isaev, Dmytro; Maximyuk, Oleksandr; Ivanchick, Gleb; Sydorenko, Vadym; Krishtal, Oleg; Isaeva, Elena

    2014-01-24

    Persistent tetrodotoxin-sensitive sodium current (INaP) plays an important role in cellular and neuronal network excitability in physiological conditions and under different pathological circumstances. However, developmental changes in INaP properties remain largely unclear. In the present study using whole cell patch clamp technique we evaluated INaP properties in CA1 hippocampal pyramidal neurons isolated from young (postnatal day (P) 12-16) and adult (P60-75) rats. We show that the INaP density is substantially larger in the adult group. Although INaP inactivation characteristics were found to be similar in both groups, voltage dependence of INaP activation is shifted to more negative membrane potentials (young: -48.6±0.5mV vs. adult: -52.4±0.2mV, p<0.01). Our data indicates the increase of INaP contribution in the basal membrane sodium conductivity in the mature hippocampus.

  13. Expression of alpha-synuclein in different brain parts of adult and aged rats.

    Science.gov (United States)

    Adamczyk, A; Solecka, J; Strosznajder, J B

    2005-03-01

    The synucleins are a family of presynaptic proteins that are abundant in neurons and include alpha-, beta, and gamma-synuclein. Alpha-synuclein (ASN) is involved in several neurodegenerative age-related disorders but its relevance in physiological aging is unknown. In the present study we investigated the expression of ASN mRNA and protein in the different brain parts of the adult (4-month-old) and aged (24-month-old) rats by using RT-PCR technique and Western blot, respectively. Our results indicated that mRNA expression and immunoreactivity of ASN is similar in brain cortex, hippocampus and striatum but markedly lower in cerebellum comparing to the other brain parts. Aging lowers ASN mRNA expression in striatum and cerebellum by about 40%. The immunoreactivity of ASN in synaptic plasma membranes (SPM) from aged brain cortex, hippocampus and cerebellum is significantly lower comparing to adult by 39%, 24% and 65%, respectively. Beta-synuclein (BSN) was not changed in aged brain comparing to adult. Age-related alteration of ASN may affect the nerve terminals structure and function.

  14. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.

    Science.gov (United States)

    Xiao, DaLiao; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Wang, Lei; Zhang, Lubo

    2015-09-01

    Previous studies have demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring.

  15. Early postnatal nociceptive stimulation results in deficits of spatial memory in male rats.

    Science.gov (United States)

    Amaral, Cristiane; Antonio, Bruno; Oliveira, Maria Gabriela Menezes; Hamani, Clement; Guinsburg, Ruth; Covolan, Luciene

    2015-11-01

    Prematurely-born infants are exposed to multiple invasive procedures while in the intensive care unit. Newborn rats and humans have similar behavioral responses to noxious stimulation. Previous studies have shown that early noxious stimuli may alter dentate gyrus neurogenesis and the behavioral repertoire of adult rats. We evaluated the late effects of noxious stimulation administered during different phases of development on two spatial memory tests; object recognition (OR) and Morris water maze (WM) tests. Noxious stimulation was induced by an intra-plantar injection of complete Freund's adjuvant (CFA) on postnatal (P) day 1 (group P1) or 8 (P8). Control animals were not stimulated. Behavioral tests were conducted on P60 in both male and female animals. In the WM, three domains were evaluated: acquisition, probe trial performance and reversal re-acquisition. The number of Nissl stained cells in the dentate granule cell layer was assessed by stereological counting. The OR test revealed that P1 male rats had poor long-term memory compared to the control and P8 groups. In the WM, no short- or long-term memory differences were detected between early postnatal-stimulated male and female rats and their respective controls. However, the ability to find the hidden platform in a new position was reduced in P1 male rats. The number of dentate granule cells in P8 males was higher than in all other groups. This study demonstrates that noxious stimulation on P1 results in spatial learning deficits in male animals, but does not disrupt the development of the hippocampus-dependent strategies of learning and memory.

  16. a-Band Oscillations in Intracellular Membrane Potentials of Dentate Gyrus Neurons in Awake Rodents

    Science.gov (United States)

    Anderson, Ross W.; Strowbridge, Ben W.

    2014-01-01

    The hippocampus and dentate gyrus play critical roles in processing declarative memories and spatial information. Dentate granule cells, the first relay in the trisynaptic circuit through the hippocampus, exhibit low spontaneous firing rates even during locomotion. Using intracellular recordings from dentate neurons in awake mice operating a…

  17. Expression of brain lipid binding protein in rat hippocampus dentate gyrus after traumatic brain injury%大鼠创伤性脑损伤后海马齿状回中脑脂结合蛋白的表达变化

    Institute of Scientific and Technical Information of China (English)

    毛伟峰; 金国华; 衣昕; 秦建兵; 田美玲

    2011-01-01

    Objective To investigate the change of brain lipid binding protein( BLBP ) expression in hippocampus dentate gyrus( DG ) at different time points after traumatic brain injury ( TBI ). Methods Seventy-two rats were divided into the injured group, sham group and control group randomly, and then were subjected to a lateral fluid percussion injury ( FPI ). Western blotting was used to detect BLBP expression. Brains were sectioned for immunofluorescence staining of BLBP and Vimentin at the time points of 1, 3, 7, 14 days after TBI. Results The results of Western blotting showed that the BLBP expression was lower than that of control group at 1 day post injury( P < 0. 01 ) and reached the peak compared with the other groups at 7 days after injury( P < 0. 01 ), then descended at 14 days compared with control group after injury( P < 0. 01 ). The changes of BLBP and Vimentin double-label positive cells were consistent with the results of Western blotting. The BLBP and Vimentin double-label positive cells were found mainly at the subgranular zone of ipsilateral injured hippocampus DG, and most of them were radial glia like cells; BLBP and Vimentin double-labelled positive cells were found at the hilus of DG at 7days after injury, and most of them looked like reactive astrocytes. Conclusion The expression of BLBP in DG after TBI decreased firstly, then increased and reached peak at 7 days after injury, decreased dramatically again at last. The phenomenon may be associated with hippocampus neurogenesis and neural rehabilitation after TBI.%目的 观察大鼠创伤性脑损伤(TBI)后不同时间点海马结构齿状回中脑脂结合蛋白(BLBP)的表达变化.方法 将72只SD大鼠随机分为脑损伤组、假手术组和空白对照组,制备大鼠颅脑液压损伤模型,伤后1、3、7、14d分别行海马组织Western blotting和BLBP、波形蛋白(Vimentin)免疫荧光双标检测.结果 Western blotting结果显示,伤后1d BLBP蛋白含量相

  18. Effect of AMPA receptors on learning and momery of the hippocampal dentate gyrus in free-moving conscious rats%AMPA受体对清醒大鼠海马齿状回区学习记忆功能的影响

    Institute of Scientific and Technical Information of China (English)

    孙志刚; 姜岩; 包金锁; 金秀吉; 金元哲; 金清华

    2009-01-01

    目的 在整体水平上揭示海马区习得性突触传递长时程增强(LTP)的形成机制,并进一步探讨谷氨酸(Glu)浓度与LTP和行为学习之间的关系.方法 使用脑部微量透析法、高效液相色谱法、慢性埋植电极技术进行电生理记录以及对学习行为监测相结合的实验方法 .结果 未进行条件反射训练大鼠海马齿状回(DG)注射α-氨基羟甲基恶唑丙酸(AMPA)受体阻断剂DNQX后,不影响DG区细胞外液中的Glu水平,但其群体峰电位(PS)幅值与给药前相比明显下降P0.05.结论 AMPA受体在海马DG区习得性LTP的形成过程中起触发作用,此受体的激活是海马DG区习得性LTP形成的必要条件.%Objective To investigate the neurochemical mechanisms responsible for learning dependent long-term potentiation (LTP), the effect of DNQX on extracellular levels of glutamate (Glu) was measured in hippocampal dentate gyrns(DG) region during the period of establishment and extinction of the conditioned reflex in free-moving conscious rats. Methods The concentrations of amino acids including Glu was measured by microdialysis and high-performance liquid chromatography (HPLC) methods and DNQX (60 nmol/L) was administrated by local-microinjection. The population spike (PS), a parameter of LTP, and conditional reflex were examined by implanted electrodes and combining electrophysiological-behavioral methods. Results There was no significant changes in the extracellular levels of Glu when local-microinjection of DNQX (60 mol/L) into the DG region without training (P > 0.05), but PS amplitude was significantly reduced (P<0.01). In the control group , the extracellular levels of Glu in the DG region were significantly increased (P < 0. 001) during the establishment of conditioned reflex and gradually returned following the extinction of conditioned reflex. The changes of Glu were correlated to the change of PS and both changes roughly follow the correct rate of behavior. Ahhough

  19. The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors.

    Science.gov (United States)

    You, Linya; Yan, Kezhi; Zou, Jinfeng; Zhou, Jinfeng; Zhao, Hong; Bertos, Nicholas R; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-03-01

    Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in leukemia, the MORF gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability. Here we show that forebrain-specific inactivation of the mouse Brpf1 gene causes hypoplasia in the dentate gyrus, including underdevelopment of the suprapyramidal blade and complete loss of the infrapyramidal blade. We trace the developmental origin to compromised Sox2+ neural stem cells and Tbr2+ intermediate neuronal progenitors. We further demonstrate that Brpf1 loss deregulates neuronal migration, cell cycle progression and transcriptional control, thereby causing abnormal morphogenesis of the hippocampus. These results link histone binding and acetylation control to hippocampus development and identify an important epigenetic regulator for patterning the dentate gyrus, a brain structure critical for learning, memory and adult neurogenesis.

  20. The oral health and attitudes to dental treatment of a dentate elderly population in Mosgiel, Dunedin.

    Science.gov (United States)

    Cautley, A J; Rodda, J C; Treasure, E T; Spears, G F

    1992-10-01

    As part of the Mosgiel Community Study, a longitudinal investigation of the health of the elderly, a dental survey was used to determine the oral health status and treatment needs, both objective and subjective, of a group of dentate older adults. Sixteen percent of the 817 subjects were dentate. Of these, 95 were available for the dental survey, and they were questioned and examined at their homes. The mean age was 77 years, and 55 percent of subjects were male; disproportionately more older males than females had retained some of their natural teeth. Seventy-two percent regularly sought dental treatment, and 39 percent felt they were in need of treatment. Few real barriers to treatment were identified, although a major obstacle preventing many from seeking treatment was their lack of perceived need. However, even the realisation that they required treatment was not sufficient cause for many to seek treatment. All subjects required some form of dental treatment. Eighty-five of the 95 subjects required at least one restoration, and 16 percent advanced restorative treatment. The frequencies of coronal and root surface caries were similar. Oral mucosal pathology was also common. Sixty-five percent of denture wearers required prosthetic treatment. Most subjects needed simple periodontal treatment, but 11 percent required advanced therapy. The main oral health problems of this group related to the simple management of plaque-related disease, and the wearing of dentures. However, 24 percent of people required complex restorative and periodontal treatment, or both.

  1. Environmental impoverishment and aging alter object recognition, spatial learning, and dentate gyrus astrocytes.

    Science.gov (United States)

    Diniz, Daniel G; Foro, César A R; Rego, Carla M D; Gloria, David A; de Oliveira, Fabio R R; Paes, Juliana M P; de Sousa, Aline A; Tokuhashi, Tatyana P; Trindade, Lucas S; Turiel, Maíra C P; Vasconcelos, Erick G R; Torres, João B; Cunnigham, Colm; Perry, Victor H; Vasconcelos, Pedro F da Costa; Diniz, Cristovam W P

    2010-08-01

    Environmental and age-related effects on learning and memory were analysed and compared with changes observed in astrocyte laminar distribution in the dentate gyrus. Aged (20 months) and young (6 months) adult female albino Swiss mice were housed from weaning either in impoverished conditions or in enriched conditions, and tested for episodic-like and water maze spatial memories. After these behavioral tests, brain hippocampal sections were immunolabeled for glial fibrillary acid protein to identify astrocytes. The effects of environmental enrichment on episodic-like memory were not dependent on age, and may protect water maze spatial learning and memory from declines induced by aging or impoverished environment. In the dentate gyrus, the number of astrocytes increased with both aging and enriched environment in the molecular layer, increased only with aging in the polymorphic layer, and was unchanged in the granular layer. We suggest that long-term experience-induced glial plasticity by enriched environment may represent at least part of the circuitry groundwork for improvements in behavioral performance in the aged mice brain.

  2. The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors.

    Directory of Open Access Journals (Sweden)

    Linya You

    2015-03-01

    Full Text Available Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1 is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in leukemia, the MORF gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability. Here we show that forebrain-specific inactivation of the mouse Brpf1 gene causes hypoplasia in the dentate gyrus, including underdevelopment of the suprapyramidal blade and complete loss of the infrapyramidal blade. We trace the developmental origin to compromised Sox2+ neural stem cells and Tbr2+ intermediate neuronal progenitors. We further demonstrate that Brpf1 loss deregulates neuronal migration, cell cycle progression and transcriptional control, thereby causing abnormal morphogenesis of the hippocampus. These results link histone binding and acetylation control to hippocampus development and identify an important epigenetic regulator for patterning the dentate gyrus, a brain structure critical for learning, memory and adult neurogenesis.

  3. Contribution of constitutively proliferating precursor cell subtypes to dentate neurogenesis after cortical infarcts

    Directory of Open Access Journals (Sweden)

    Oberland Julia

    2010-11-01

    Full Text Available Abstract Background It is well known that focal ischemia increases neurogenesis in the adult dentate gyrus of the hippocampal formation but the cellular mechanisms underlying this proliferative response are only poorly understood. We here investigated whether precursor cells which constitutively proliferate before the ischemic infarct contribute to post-ischemic neurogenesis. To this purpose, transgenic mice expressing green fluorescent protein (GFP under the control of the nestin promoter received repetitive injections of the proliferation marker bromodeoxyuridine (BrdU prior to induction of cortical infarcts. We then immunocytochemically analyzed the fate of these BrdU-positive precursor cell subtypes from day 4 to day 28 after the lesion. Results Quantification of BrdU-expressing precursor cell populations revealed no alteration in number of radial glia-like type 1 cells but a sequential increase of later precursor cell subtypes in lesioned animals (type 2a cells at day 7, type 3 cells/immature neurons at day 14. These alterations result in an enhanced survival of mature neurons 4 weeks postinfarct. Conclusions Focal cortical infarcts recruit dentate precursor cells generated already before the infarct and significantly contribute to an enhanced neurogenesis. Our findings thereby increase our understanding of the complex cellular mechanisms of postlesional neurogenesis.

  4. Melatonin ameliorates dexamethasone-induced inhibitory effects on the proliferation of cultured progenitor cells obtained from adult rat hippocampus.

    Science.gov (United States)

    Ekthuwapranee, Kasima; Sotthibundhu, Areechun; Tocharus, Chainarong; Govitrapong, Piyarat

    2015-01-01

    Glucocorticoids, hormones that are released in response to stress, induce neuronal cell damage. The hippocampus is a primary target of glucocorticoids in the brain, the effects of which include the suppression of cell proliferation and diminished neurogenesis in the dentate gyrus. Our previous study found that melatonin, synthesized primarily in the pineal, pretreatment prevented the negative effects of dexamethasone, the glucocorticoid receptor agonist, on behavior and neurogenesis in rat hippocampus. In the present study, we attempted to investigate the interrelationship between melatonin and dexamethasone on the underlying mechanism of neural stem cell proliferation. Addition of dexamethasone to hippocampal progenitor cells from eight-week old rats resulted in a decrease in the number of neurospheres; pretreatment with melatonin precluded these effects. The immunocytochemical analyses indicated a reduction of Ki67 and nestin-positive cells in the dexamethasone-treated group, which was minimized by melatonin pretreatment. A reduction of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation and G1-S phase cell cycle regulators cyclin E and CDK2 in dexamethasone-treated progenitor cells were prevented by pretreatment of melatonin. Moreover, luzindole, a melatonin receptor antagonist blocked the positive effect of melatonin whereas RU48, the glucocorticoid receptor antagonist blocked the negative effect of dexamethasone on the number of neurospheres. Moreover, we also found that dexamethasone increased the glucocorticoid receptor protein but decreased the level of MT1 melatonin receptor, whereas melatonin increased the level of MT1 melatonin receptor but decreased the glucocorticoid receptor protein. These suggest the crosstalk and cross regulation between the melatonin receptor and the glucocorticoid receptor on hippocampal progenitor cell proliferation.

  5. Histological studies of the effects of monosodium glutamate of the Fallopian tubes of adult female Wistar rats

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-01-01

    Full Text Available Background: The effect of monosodium glutamate used as food additive on the fallopian tubes of adult Wistar rat was investigated. Material and Methods: Adult female Wistar rats (n=24 of average weight of 230g were randomly assigned into three groups A, B and C in each group (n=8. The treatment groups (A & B were given 0.04mg/kg and 0.08mg/kg of monosodium glutamate thoroughly mixed with the growers′ mash, respectively on a daily basis. The control group (C received equal amount of feeds (Growers′ mash without monosodium glutamate added for fourteen days. The growers′ mash was obtained from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and the rats were given water liberally. The rats were sacrificed on day fifteen of the experiment. The fallopian tubes were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological procedures. Result: The histological findings in the treated groups showed evidence of cellular hypertrophy, degenerative and atrophic changes, and lysed red blood cells in lumen with the group that received 0.08mg/kg of monosodium glutamate more severe. Conclusion: MSG may have some deleterious effects on the fallopian tubes of adult female Wistar rats at higher doses and by extension may contribute to the causes of female infertility. It is recommended that further studies aimed at corroborating these findings be carried out.

  6. Massively augmented hippocampal dentate granule cell activation accompanies epilepsy development

    Science.gov (United States)

    Dengler, Christopher G.; Yue, Cuiyong; Takano, Hajime; Coulter, Douglas A.

    2017-01-01

    In a mouse model of temporal lobe epilepsy, multicellular calcium imaging revealed that disease emergence was accompanied by massive amplification in the normally sparse, afferent stimulation-induced activation of hippocampal dentate granule cells. Patch recordings demonstrated reductions in local inhibitory function within the dentate gyrus at time points where sparse activation was compromised. Mimicking changes in inhibitory synaptic function and transmembrane chloride regulation was sufficient to elicit the dentate gyrus circuit collapse evident during epilepsy development. Pharmacological blockade of outward chloride transport had no effect during epilepsy development, and significantly increased granule cell activation in both control and chronically epileptic animals. This apparent occlusion effect implicates reduction in chloride extrusion as a mechanism contributing to granule cell hyperactivation specifically during early epilepsy development. Glutamine plays a significant role in local synthesis of GABA in synapses. In epileptic mice, sparse granule cell activation could be restored by glutamine application, implicating compromised GABA synthesis. Glutamine had no effect on granule cell activation earlier, during epilepsy development. We conclude that compromised feedforward inhibition within the local circuit generates the massive dentate gyrus circuit hyperactivation evident in animals during and following epilepsy development. However, the mechanisms underlying this disinhibition diverge significantly as epilepsy progresses. PMID:28218241

  7. TIME COURSE OF CHOLINESTERASE INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL CARBOFURAN, FORMETANATE, METHOMYL, METHIOCARB, OXAMYL ON PROPOXUR.

    Science.gov (United States)

    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); ...

  8. Effects of chronic overload on muscle hypertrophy and mTOR signaling in adult and aged rats

    Science.gov (United States)

    We examined the effect of 28 days of overload on mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling in young adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two-thirds of the gas...

  9. Effect of neonatal or adult heat acclimation on testicular and epididymal morphometry and sperm production in rats.

    Science.gov (United States)

    Kurowicka, B; Dietrich, G J; Kotwica, G

    2015-03-01

    The accessory gland weight, testicular and epididymal morphometry and sperm production were analyzed in four groups of rats housed at 20 or 34°C: (1) control rats (CR) kept at 20°C from birth to day 90; (2) adult heat-acclimated rats (AHA) kept at 20°C from birth to day 45 followed by 34°C to day 90; (3) neonatal heat-acclimated rats (NHA) kept at 34°C from birth to day 90 and (4) de-acclimated rats (DA) kept at 34°C from birth to day 45 followed by 20°C to day 90. In NHA and DA rats, accessory gland weight was higher than in controls. Despite the lack of differences in testicular and epididymal morphometry, curvilinear velocity of spermatozoa was lower in the NHA group compared to controls. Areas of seminiferous tubules were lower in the DA than in CR and NHA groups, however, sperm concentration and motility were not affected by the treatment in this group. In AHA rats, epithelium of approximately 20% of seminiferous tubules was degenerated and Sertoli cell number was lower in the remaining tubules. In contrast to sperm motility, epididymal duct area, area of the duct occupied by spermatozoa and cauda epididymis sperm concentration were lower in AHA rats than in the other groups. In conclusion, neonatal heat acclimation did not affect the testicular morphometry and epididymal sperm concentration, suggesting adjustment to high ambient temperature. On the contrary, adult heat acclimation of rats affected the examined parameters, leading to decreased sperm concentration.

  10. Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain.

    Directory of Open Access Journals (Sweden)

    Anke Popp

    Full Text Available BACKGROUND: GABA (gamma-aminobutyric acid, the main inhibitory neurotransmitter in the brain, is synthesized by glutamic acid decarboxylase (GAD. GAD exists in two adult isoforms, GAD65 and GAD67. During embryonic brain development at least two additional transcripts exist, I-80 and I-86, which are distinguished by insertions of 80 or 86 bp into GAD67 mRNA, respectively. Though it was described that embryonic GAD67 transcripts are not detectable during adulthood there are evidences suggesting re-expression under certain pathological conditions in the adult brain. In the present study we systematically analyzed for the first time the spatiotemporal distribution of different GADs with emphasis on embryonic GAD67 mRNAs in the postnatal brain using highly sensitive methods. METHODOLOGY/PRINCIPAL FINDINGS: QPCR was used to precisely investigate the postnatal expression level of GAD related mRNAs in cortex, hippocampus, cerebellum, and olfactory bulb of rats from P1 throughout adulthood. Within the first three postnatal weeks the expression of both GAD65 and GAD67 mRNAs reached adult levels in hippocampus, cortex, and cerebellum. The olfactory bulb showed by far the highest expression of GAD65 as well as GAD67 transcripts. Embryonic GAD67 splice variants were still detectable at birth. They continuously declined to barely detectable levels during postnatal development in all investigated regions with exception of a comparatively high expression in the olfactory bulb. Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream. CONCLUSIONS/SIGNIFICANCE: Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity. Therefore a functional role in processes like proliferation, migration or

  11. Effects of juvenile isolation and morphine treatment on social interactions and opioid receptors in adult rats: behavioural and autoradiographic studies.

    Science.gov (United States)

    Van den Berg, C L; Van Ree, J M; Spruijt, B M; Kitchen, I

    1999-09-01

    The consequences of juvenile isolation and morphine treatment during the isolation period on (social) behaviour and mu-, delta- and kappa-opioid receptors in adulthood were investigated by using a social interaction test and in vitro autoradiography in rats. Juvenile isolation reduced social exploration in adults. Morphine treatment counteracted this reduction in isolated rats, but decreased social exploration in nonisolated rats. Self-grooming and nonsocial exploration were enhanced after juvenile isolation. Morphine treatment had no effect on self-grooming, but suppressed nonsocial exploration in isolated rats. With respect to the opioid receptors, juvenile isolation resulted in regiospecific increases in mu-binding sites with a 58% increase in the basolateral amygdala and a 33% increase in the bed nucleus of stria terminalis. Morphine treatment in isolated rats reversed this upregulation in both areas. The number of delta-binding sites did not differ between the experimental groups. A general upregulation of kappa-binding sites was observed after juvenile isolation, predominantly in the cortical regions, the hippocampus and the substantia nigra. Morphine treatment did not affect the upregulation of kappa-receptors. The results show that juvenile isolation during the play period causes long-term effects on social and nonsocial behaviours and on the number of mu- and kappa- but not delta-opioid receptors in distinct brain areas. The number of mu-receptors in the basolateral amygdala appears to be negatively correlated with the amount of social exploration in adult rats.

  12. Effect of light-dark changes on the locomotor activity in open field in adult rats and opossums.

    Science.gov (United States)

    Klejbor, I; Ludkiewicz, B; Turlejski, K

    2013-11-01

    There have been no reports on how the light-dark changes determine the locomotor activity of animals in the group of high reactivity (HR) and low reactivity (LR). In the present study we have compared selected parameters of the locomotor activity of the HR and the LR groups of the laboratory opossums and Wistar rats during consecutive, light and dark phases in the open field test. Sixty male Wistar adult rats, at an average weight of 350 g each, and 24 adult Monodelphis opossums of both sexes at an average weight of 120 g each were used. The animals' activity for 2 h daily between the hours of 17:30 and 19:30, in line with the natural light-dark cycle were recorded and then analysed using VideoTrack ver.2.0 (Vievpoint France). According to our results, we noted that a change of the experimental conditions from light to dark involves an increase in the locomotor activity in rats and opossums of the HR group, while there is no effect on the activity of the rats and opossums in the LR group. Locomotor activity in the HR rats, both in the light and dark conditions is characterised by a consistent pattern of change - higher activity in the first stage of the recording and a slowdown (habituation) in the second phase of the observation. The locomotor activity of the opossum, during both light and dark conditions, was observed to be at a consistently high level compared to the rats.

  13. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    Science.gov (United States)

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one.

  14. Cellular distribution and localisation of iron in adult rat brain (substantia nigra)

    Energy Technology Data Exchange (ETDEWEB)

    Meinecke, Ch. [Institute for Experimental Physics II, Faculty for Physics and Geosciences, University of Leipzig, Linnestr. 5, D-04103 Leipzig (Germany)]. E-mail: meinecke@physik.uni-leipzig.de; Morawski, M. [Paul-Flechsig-Institute for Brain research, University of Leipzig, Jahnallee 59, D-04109 Leipzig (Germany); Reinert, T. [Institute for Experimental Physics II, Faculty for Physics and Geosciences, University of Leipzig, Linnestr. 5, D-04103 Leipzig (Germany); Arendt, T. [Paul-Flechsig-Institute for Brain research, University of Leipzig, Jahnallee 59, D-04109 Leipzig (Germany); Butz, T. [Institute for Experimental Physics II, Faculty for Physics and Geosciences, University of Leipzig, Linnestr. 5, D-04103 Leipzig (Germany)

    2006-08-15

    Iron appears to be one of the main factors in the metal induced neurodegeneration. Quantitative information on cellular, sub-cellular and cell specific distributions of iron is therefore important to assess. The investigations reported here were carried out on a brain from an adult rat. Therefore, 6 {mu}m thick embedded, unstained brain sections containing the midbrain (substantia nigra, SN) were analysed. Particle induced X-ray emission (PIXE) using a focussed proton beam (beam - diameter app. 1 {mu}m) was performed to determine the quantitative iron content on a cellular and sub-cellular level. The integral analysis shows that the iron content in the SN pars reticulata is twice as high than in the SN pars compacta. The analysis of the iron content on the cellular level revealed no remarkable differences between glia cells and neurons. This is in contrast to other studies using staining techniques.

  15. ACQUISITION OF FREEZING RESPONSE IN RATS: SEX DIFFERENCES IN ADOLESCENTS AND ADULTS

    Directory of Open Access Journals (Sweden)

    Cristina Vargas-Irwin

    2011-12-01

    Full Text Available Pavlovian fear conditioning is one of the most popular preclinical models in the studyof Post-Traumatic Stress Disorder (PTSD. The aim of the present research wasexplore the sex differences that characterize PTSD by means of this experimentalparadigm, as well as to offer a preliminary description of how these sex differencesbehave throughout development. Forty five naïve rats, of Wistar descent were usedas subjects, with 18 males and 27 females approximately balanced by litter acrossthe two experimental groups: adolescents and adults. The results show significantdifferences in the second measurement of the conditioned stimulus in the interactionbetween sex and age and to compare the tree measurements of the conditionedstimulus. Results are discussed regarding the discrepancies in the literature regardingthe effect of the variables evaluated in the acquisition of Conditioned fear.

  16. Systemic physiology and neuroapoptotic profiles in young and adult rats exposed to surgery

    DEFF Research Database (Denmark)

    Ibrahim, Rami Mossad; Krammer, Caspar Weel; Hansen, Tom Giedsing;

    2015-01-01

    to one of four anaesthetics regimens: (i) sevoflurane/dexmedetomidine, (ii) sevoflurane/fentanyl; (iii) propofol/dexmedetomidine, and (iv) propofol/fentanyl. Animals underwent a dorsal skin flap procedure while physiologic, metabolic and biochemical parameters were closely monitored. Neuroapoptotic...... of sevoflurane and dexmedetomidine resulted in the highest number of caspase-3 positive cells, although the extent of cell death remained relatively low in all experimental groups. CONCLUSION: Combination of anaesthesia and surgery induces significant perturbations of physiological parameters in both young...... and adult spontaneously breathing rats undergoing surgery. These observations further enlighten the need for detailed physiological monitoring under these experimental conditions. Although some statistically significant differences in activated caspase-3 profiles were detected between experimental groups...

  17. Electroconvulsive Stimulation, but not Chronic Restraint Stress, Causes Structural Alterations in Adult Rat Hippocampus

    DEFF Research Database (Denmark)

    Olesen, Mikkel V.; Wörtwein, Gitta; Pakkenberg, Bente

    2015-01-01

    The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible...... changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number...... induces depression-like behavior, without significantly changing neurogenesis, the total number of neurons or the volume of the hippocampus. Further, electroconvulsive stimulation prevents stress-induced depression-like behavior and increases neurogenesis. The total number of neurons and the granule cell...

  18. Dissociable effects of ethanol consumption during the light and dark phase in adolescent and adult Wistar rats.

    Science.gov (United States)

    Walker, Brendan M; Walker, Jennifer L; Ehlers, Cindy L

    2008-03-01

    In adolescence, high levels of drinking over short episodes (binge drinking) is commonly seen in a proportion of the population. Because adolescence is an important neurodevelopmental period, the effects of binge drinking on brain and behavior has become a significant health concern. However, robust animal models of binge drinking in rats are still being developed and therefore further efforts are needed to optimize paradigms for inducing maximal self-administration of alcohol. In the present experiment, 1-h limited-access self-administration sessions were instituted to model excessive drinking behavior in adolescent and adult Wistar rats. In addition to age, the involvement of sex and phase within the light/dark cycle (i.e., drinking in the light or dark) on sweetened 5% ethanol intake were also evaluated over 14 limited-access sessions using a between-groups design. The results of the experiment showed that over 14 limited-access sessions, sweetened ethanol intake (g/kg) was significantly higher for adolescents compared to adults. Females were also found to drink more sweetened ethanol as compared to males. Additionally, drinking in the light produced a robust increase in sweetened ethanol intake (g/kg) in adolescents, as compared to adults during the light phase and as compared to both adolescent and adult rats drinking in the dark. Furthermore, the increase in ethanol consumption observed in adolescents drinking during the light phase was dissociable from sweetened solution intake patterns. These results identify that age, sex, and time of day all significantly influence consumption of sweetened ethanol in Wistar rats. Knowledge of these parameters should be useful for future experiments attempting to evaluate the effects of self-administered ethanol exposure in adult and adolescent rats.

  19. Behavioral differences between late preweanling and adult female Sprague-Dawley rat exploration of animate and inanimate stimuli and food.

    Science.gov (United States)

    Smith, Kiersten S; Morrell, Joan I

    2011-03-01

    The late preweanling rat has potential as a preclinical model for disorders initially manifested in early childhood that are characterized by dysfunctional interactions with specific stimuli (e.g., obsessive-compulsive disorder and autism). No reports, however, of specific-stimulus exploration in the late preweanling rat are found in the literature. We examined the behavioral responses of normal late preweanling (PND 18-19) and adult rats when presented with exemplars of categorically-varied stimuli, including inanimate objects systematically varied in size and interactive properties, biological stimuli, and food. Preweanlings were faster to initiate specific stimulus exploration and were more interactive with most specific stimuli than adults; the magnitude of these preweanling-adult quantitative differences ranged from fairly small to very large depending upon the stimulus. In contrast, preweanlings were adult-like in their interaction with food and prey. Preweanling response to some stimuli, for example to live pups, was qualitatively different from that of adults; the preweanling behavioral repertoire was characterized by pup-seeking while the adult response was characterized by pup-avoidance. The specific stimulus interactions of preweanlings were less impacted than those of adults by the time of day of testing and placement of a stimulus in an anxiety-provoking location. The impact of novelty was stimulus dependent. The differences in interactions of preweanlings versus adults with specific stimuli suggests that CNS systems underlying these behavior patterns are at different stages of immaturity at PND 18 such that there may be an array of developmental trajectories for various categories of specific stimuli. These data provide a basis for the use of the preweanling as a preclinical model for understanding and medicating human disorders during development that are characterized by dysfunctional interactions with specific stimuli.

  20. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol

    Energy Technology Data Exchange (ETDEWEB)

    Akane, Hirotoshi [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Saito, Fumiyo [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Shiraki, Ayako [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Takeyoshi, Masahiro; Imatanaka, Nobuya [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Itahashi, Megu [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Murakami, Tomoaki [Laboratory of Veterinary Toxicology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200 mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200 mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc{sup +} neurons at 1000 ppm and Fos{sup +} neurons at ≥ 300 ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure. - Highlights: • Neuronal toxicity parameters after 28-day glycidol treatment were examined in rats. • Region-specific global gene expression profiling was conducted in brain regions. • Cortical tissues downregulated genes on axonogenesis and synaptic transmission. • Cortical tissues

  1. Deletion of the NMDA receptor GluN2A subunit significantly decreases dendritic growth in maturing dentate granule neurons.

    Directory of Open Access Journals (Sweden)

    Timal S Kannangara

    Full Text Available It is known that NMDA receptors can modulate adult hippocampal neurogenesis, but the contribution of specific regulatory GluN2 subunits has been difficult to determine. Here we demonstrate that mice lacking GluN2A (formerly NR2A do not show altered cell proliferation or neuronal differentiation, but present significant changes in neuronal morphology in dentate granule cells. Specifically, GluN2A deletion significantly decreased total dendritic length and dendritic complexity in DG neurons located in the inner granular zone. Furthermore, the absence of GluN2A also resulted in a localized increase in spine density in