Adult Rat Brain (adult + rat_brain)

Distribution by Scientific Domains


Selected Abstracts


Intrauterine proximity to male fetuses affects the morphology of the sexually dimorphic nucleus of the preoptic area in the adult rat brain

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2006
Minjuan Pei
Abstract Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17,-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17,-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains. [source]


Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006
Tania Ramos-Moreno
Abstract Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal (,perforant') path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits. [source]


Cellular prion protein/laminin receptor: distribution in adult central nervous system and characterization of an isoform associated with a subtype of cortical neurons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2004
Hasna Baloui
Abstract The 67-kDa LR protein was originally discovered as a non-integrin laminin receptor. Several more recent in vitro studies demonstrated the function of 67-kDa LR and its related ,precursor' form 37-kDa LRP as receptors of cellular prion protein and their implication in abnormal prion protein propagation in vitro. In addition, expression of both proteins was shown to increase considerably in the brain of scrapie-infected mice and hamsters. While LRP/LR are thus likely to play important roles in neuronal cell adhesion, survival and homeostasis and during pathological disorders, little is known so far about their fine cellular distribution in adult central nervous system. Using immunocytochemistry and western blotting, we show here that the 67-kDa LR is the major receptor form in adult rat brain and spinal cord, expressed within the cytoplasm and at the plasma membrane of most neurons and in a subset of glial cells. The overall distribution of LR correlates well with that reported for laminin-1 but also with brain regions classically associated with prion-related neurodegeneration. In contrast to LR, the 37-kDa LRP form is much less abundant in adult than in postnatal central nervous system. Characterization of a novel antibody allowed us to study the distribution across tissues of cell membrane-associated LRP. Interestingly, this form is almost exclusively found on a subclass of parvalbumin-immunoreactive cortical interneurons known to degenerate during the early stages of Creutzfeldt-Jakob disease. Our demonstration of local differences in the expression of particular LRP/LR isoforms may be a first step towards unraveling their specific molecular interactions. [source]


Selective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medial prefrontocortical dendrites: implications for stress-related cortical pathology?

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2002
A. Trentani
Abstract Stress has been shown to affect brain structural plasticity, promote long-term changes in multiple neurotransmitter systems and cause neuronal atrophy. However, the mechanisms involved in these stress-related neural alterations are still poorly understood. Mitogen-activated protein kinase (MAPK) cascades play a crucial role in the transduction of neurotrophic signal from the cell surface to the nucleus and are implicated in the modulation of synaptic plasticity and neuronal survival. An intriguing possibility is that stress might influence brain plasticity through its effects on selective members of such intracellular signalling cascades responsible for the transduction of neurotrophin signals. Here, we have investigated the effects of stress on the expression of three members of the MAPK/extracellular-regulated kinase (ERK) pathway such as phospho-ERK1, phospho-ERK2 and phospho-cAMP/calcium-responsive element-binding protein (CREB) in the adult rat brain. Male rats were subjected to mild footshocks and the patterns of protein expression were analysed after 21 consecutive days of stress. We found that chronic stress induced a pronounced and persistent ERK1/2 hyperphosphorylation in dendrites of the higher prefrontocortical layers (II and III) and a reduction of phospho-CREB expression in several cortical and subcortical regions. We hypothesized that defects in ERK signalling regulation combined with a reduced phospho-CREB activity may be a crucial mechanism by which sustained stress may induce atrophy of selective subpopulations of vulnerable cortical neurons and/or distal dendrites. Thus, ERK-mediated cortical abnormalities may represent a specific path by which chronic stress affects the functioning of cortical structures and causes selective neural network defects. [source]


Postnatal handling alters the activation of stress-related neuronal circuitries

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000
István M. Ábrahám
Abstract Postnatal handling, as a crucial early life experience, plays an essential role in the development of hypothalamo-pituitary,adrenal axis responses to stress. The impact of postnatal handling on the reactivity of stress-related neuronal circuitries was investigated in animals that were handled for the first 21 days of life and as adults they were exposed to physical (ether) or emotional (restraint) challenge. To assess neuronal activation we relied on the induction of immediate-early gene product c-Fos and analysed its spatial and temporal distribution at various time intervals after stress. Ether and restraint commonly activated parvocellular neurons in the hypothalamic paraventricular nucleus, and resulted in activation of brain areas providing stress-related information to the hypothalamic effector neurons and/or in regions governing autonomic and behavioural responses to stress. Beyond these areas, the strength and timing of c-Fos induction showed stressor specificity in olfactory and septal region, basal ganglia, hypothalamus, hippocampal formation, amygdala and brainstem. Handled rats displayed a lower number of c-Fos-positive cell nuclei and weaker staining intensity than non-handled controls in the hypothalamic paraventricular nucleus, bed nucleus of stria terminalis, central nucleus of amygdala, hippocampus, piriform cortex and posterior division of the cingulum. Significant differences were revealed in timing of c-Fos induction as a function of stressor and early life experience. Together, these data provide functional anatomical evidence that environmental enrichment in the early postnatal period attenuates the reactivity of stress-related neuronal circuitries in the adult rat brain. [source]


The chondroitin sulphate proteoglycan brevican is upregulated by astrocytes after entorhinal cortex lesions in adult rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2000
Niklas Thon
Abstract The chondroitin sulphate proteoglycan brevican is one of the most abundant extracellular matrix molecules in the adult rat brain. It is primarily synthesized by astrocytes and is believed to influence astroglial motility during development and under certain pathological conditions. In order to study a potential role of brevican in the glial reaction after brain injury, its expression was analysed following entorhinal cortex lesion in rats (12 h, 1, 2, 4, 10, 14 and 28 days and 6 months post lesion). In situ hybridization and immunohistochemistry were employed to study brevican mRNA and protein, respectively, in the denervated outer molecular layer of the fascia dentata and at the lesion site. In both regions brevican mRNA was upregulated between 1 and 4 days post lesion. The combination of in situ hybridization with immunohistochemistry for glial fibrillary acidic protein demonstrated that many brevican mRNA-expressing cells are astrocytes. In the denervated zone of the fascia dentata, immunostaining for brevican was increased by 4 days, reached a maximum by 4 weeks and remained detectable up to 6 months post lesion. Electron microscopic immunocytochemistry showed that brevican is a component of the extracellular matrix compartment. At the lesion site a similar time course of brevican upregulation was observed. These data demonstrate that brevican is upregulated in areas of brain damage as well as in areas denervated by a lesion. They suggest a role of brevican in reactive gliosis and are compatible with the hypothesis that brevican is involved in the synaptic reorganization of denervated brain areas. [source]


NG2 proteoglycan-expressing cells of the adult rat brain: Possible involvement in the formation of glial scar astrocytes following stab wound

GLIA, Issue 3 2005
G. Alonso
Abstract Stab wound lesion to the adult central nervous system induces strong proliferative response that is followed by the formation of a dense astroglial scar. In order to determine the origin of those astrocytes composing the glial scar, the cell proliferation marker bromodeoxyuridine (BrdU) was administered to lesioned rats that were fixed 3 h or 6 days later. At 3 h after the BrdU administration, labeled nuclei were frequently associated with either NG2+ cells or microglia/macrophages, but rarely with astrocytes expressing glial fibrillary acidic protein (GFAP). Six days later, by contrast, numerous BrdU-labeled nuclei were associated with astrocytes located along the lesion borders. After the injection of a viral vector of the green fluorescent protein (GFP) into the lesional cavity, GFP was preferentially detected within NG2- or GFAP-labeled cells when lesioned animals were fixed 1 or 6 days after the injections, respectively. The combined detection of glial markers within cells present in the lesioned area indicated that, although they rarely express GFAP, the marker of mature astrocytes, NG2+ cells located along the lesion borders frequently express nestin and vimentin, i.e., two markers of immature astrocytes. Lastly, chronic treatment of lesioned rats with dexamethasone was found to inhibit the proliferation of NG2+ cells present within the lesioned area and to subsequently alter the formation of a dense astroglial scar. Taken together, these data strongly suggest that following a surgical lesion, at least a portion of the astrocytes that constitute the glial scar are issued from resident NG2+ cells. © 2004 Wiley-Liss, Inc. [source]


Chlorotoxin-sensitive Ca2+ -activated Cl, channel in type R2 reactive astrocytes from adult rat brain

GLIA, Issue 4 2003
Stanislava Dalton
Abstract Astrocytes express four types of Cl, or anion channels, but Ca2+ -activated Cl, (ClCa) channels have not been described. We studied Cl, channels in a morphologically distinct subpopulation (, 5% of cells) of small (10,12 ,m, 11.8 ± 0.6 pF), phase-dark, GFAP-positive native reactive astrocytes (NRAs) freshly isolated from injured adult rat brains. Their resting potential, ,57.1 ± 4.0 mV, polarized to ,72.7 ± 4.5 mV with BAPTA-AM, an intracellular Ca2+ chelator, and depolarized to ,30.7 ± 6.1 mV with thapsigargin, which mobilizes Ca2+ from intracellular stores. With nystatin-perforated patch clamp, thapsigargin activated a current that reversed near the Cl, reversal potential, which was blocked by Cl, channel blockers, 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and Zn2+, by I, (10 mM), and by chlorotoxin (EC50 = 47 nM). With conventional whole-cell clamp, NPPB- and Zn2+ -sensitive currents became larger with increasing [Ca2+]i (10, 150, 300 nM). Single-channel recordings of inside-out patches confirmed Ca2+ sensitivity of the channel and showed open-state conductances of 40, 80, 130, and 180 pS, and outside-out patches confirmed sensitivity to chlorotoxin. In primary culture, small phase-dark NRAs developed into small GFAP-positive bipolar cells with chlorotoxin-sensitive ClCa channels. Imaging with biotinylated chlorotoxin confirmed the presence of label in GFAP-positive cells from regions of brain injury, but not from uninjured brain. Chlorotoxin-tagged cells isolated by flow cytometry and cultured up to two passages exhibit positive labeling for GFAP and vimentin, but not for prolyl 4-hydroxylase (fibroblast), A2B5 (O2A progenitor), or OX-42 (microglia). Expression of a novel chlorotoxin-sensitive ClCa channel in a morphologically distinct subpopulation of NRAs distinguishes these cells as a new subtype of reactive astrocyte. GLIA 42:325,339, 2003. © 2003 Wiley-Liss, Inc. [source]


Proliferation of progenitor cells in the adult rat brain correlates with the presence of vimentin-expressing astrocytes

GLIA, Issue 4 2001
Gérard Alonso
Abstract It is well established that proliferation of progenitor cells persists within the hippocampal dentate gyrus (DG) and the subventricular zone of the lateral ventricle (SVZ) in the adult brain. The aim of the present study was to determine whether the rate of cell proliferation within these germinative zones could be correlated to the occurrence of a particular glial environment. The cell proliferation marker bromodeoxyuridine (BrdU) was administrated to rats under different physiological and experimental conditions known to modify the rate of progenitor cell proliferation. Within both germinative zones, BrdU-labeled nuclei were associated with cell bodies immunostained for the neuronal marker polysialylated neural cell adhesion molecule, but not for the glial markers glial fibrillary acidic protein (GFAP) or vimentin (VIM). In all the rats examined, however, proliferating (BrdU-labeled) cells always exhibited close relationships with immature-like astrocytes that expressed both GFAP and VIM. There was a dramatic decrease of cell proliferation in the DG from both the aged rats and the corticosterone-treated adult rats that was correlated with a decreased expression of vimentin by the astrocytes present in this region. In contrast, both cell proliferation and vimentin expression were only slightly affected in the SVZ from these two treatment groups. Conversely, after either adrenalectomy or a surgical lesion through the lateral hippocampus, the increase in cell proliferation observed in the DG was correlated to the occurrence of an increased number of GFAP and VIM double immunostained structures in these regions. All together, these data suggest that immature-like astrocytes present in the germinative zones may provide a microenvironment involved in sustaining the proliferation of progenitor cells. GLIA 34:253,266, 2001. © 2001 Wiley-Liss, Inc. [source]


Restricted, but abundant, expression of the novel rat gene-3 (R3) relaxin in the dorsal tegmental region of brain

JOURNAL OF NEUROCHEMISTRY, Issue 6 2002
Tanya C. D. Burazin
Abstract Relaxin is a peptide hormone with known actions associated with female reproductive physiology, but it has also been identified in the brain. Only one relaxin gene had been characterized in rodents until recently when a novel human relaxin gene, human gene-3 (H3) and its mouse equivalent (M3) were identified. The current study reports the identification of a rat homologue, rat gene-3 (R3) relaxin that is highly expressed in a discrete region of the adult brain. The full R3 relaxin cDNA was generated using RT-PCR and 3, and 5, RACE protocols. The derived amino acid sequence of R3 relaxin retains all the characteristic features of a relaxin peptide and has a high degree of homology with H3 and M3 relaxin. The distribution of R3 relaxin mRNA in adult rat brain was determined and highly abundant expression was only detected in neurons of the ventromedial dorsal tegmental nucleus (vmDTg) in the pons, whereas all other brain areas were unlabelled or contained much lower mRNA levels. Relaxin binding sites and relaxin immunoreactivity were also detected in the vmDTg. These together with earlier findings provide strong evidence for a role(s) for multiple relaxin peptides as neurotransmitters and/or modulators in the rat CNS. [source]


Non-homologous DNA end joining in the mature rat brain

JOURNAL OF NEUROCHEMISTRY, Issue 6 2002
Keqin Ren
Abstract Recent evidence suggests that DNA double strand breaks (DSBs) are introduced in neurons during the course of normal development, and that repair of such DSBs is essential for neuronal survival. Here we describe a non-homologous DNA end joining (NHEJ) system in the adult rat brain that may be used to repair DNA DSBs. In the brain NHEJ system, blunt DNA ends are joined with lower efficiency than cohesive or non-matching protruding ends. Moreover, brain NHEJ is blocked by DNA ligase inhibitors or by dATP and can occur in the presence or absence of exogenously added ATP. Comparison of NHEJ activities in several tissues showed that brain and testis share similar mechanisms for DNA end joining, whereas the activity in thymus seems to utilize different mechanisms than in the nervous system. The developmental profile of brain NHEJ showed increasing levels of activity after birth, peaking at postnatal day 12 and then gradually decreasing along with age. Brain distribution analysis in adult animals showed that NHEJ activity is differentially distributed among different regions. We suggest that the DNA NHEJ system may be utilized in the postnatal brain for the repair of DNA double strand breaks introduced within the genome in the postnatal brain. [source]


Content of endoplasmic reticulum and Golgi complex membranes positively correlates with the proliferative status of brain cells

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2009
David C. Silvestre
Abstract Although the molecular and cellular basis of particular events that lead to the biogenesis of membranes in eukaryotic cells has been described in detail, understanding of the intrinsic complexity of the pleiotropic response by which a cell adjusts the overall activity of its endomembrane system to accomplish these requirements is limited. Here we carried out an immunocytochemical and biochemical examination of the content and quality of the endoplasmic reticulum (ER) and Golgi apparatus membranes in two in vivo situations characterized by a phase of active cell proliferation followed by a phase of declination in proliferation (rat brain tissue at early and late developmental stages) or by permanent active proliferation (gliomas and their most malignant manifestation, glioblastomas multiforme). It was found that, in highly proliferative phases of brain development (early embryo brain cells), the content of ER and Golgi apparatus membranes, measured as total lipid phosphorous content, is higher than in adult brain cells. In addition, the concentration of protein markers of ER and Golgi is also higher in early embryo brain cells and in human glioblastoma multiforme cells than in adult rat brain or in nonpathological human brain cells. Results suggest that the amount of endomembranes and the concentration of constituent functional proteins diminish as cells decline in their proliferative activity. © 2008 Wiley-Liss, Inc. [source]


Role of glial metabolism in diabetic encephalopathy as detected by high resolution 13C NMR

NMR IN BIOMEDICINE, Issue 6-7 2003
María A. García-Espinosa
Abstract The roles of glial energetics and of the glutamine cycle in diabetic encephalopathy have been investigated ex vivo by 13C NMR in extracts of adult rat brain. Streptozotocin-induced diabetic or euglycemic animals received intravenous infusions of (1- 13C) glucose in the absence and presence of trifluoroacetic acid or methionine sulfoximine, two selective inhibitors of the glial tricarboxylic acid cycle or of glutamine synthase, respectively. (1- 13C) glucose infusions resulted in smaller 13C incorporation in all carbons of cerebral glutamate, glutamine and GABA in the diabetic animals. Co-infusion of trifluoroacetic acid with (1- 13C) glucose further reduced the 13C enrichments in cerebral glutamate and glutamine, the decrease being larger in the diabetic animals than in the corresponding euglycemic controls. Methionine sulfoximine decreased to undetectable levels the fractional 13C enrichment in the carbons of cerebral glutamine in both groups and had no significant effect on 13C incorporation in glutamate and GABA, suggesting that glutamine is not the main precursor of glutamate and GABA. Additional animals were infused with (1,2- 13C2) acetate, a major substrate of glial metabolism. In this case, (1,2- 13C2) acetate infusions resulted in increased 13C incorporation in all carbons of glutamate, glutamine and GABA in the diabetic animals. Together, these results reveal that diabetic encephalopathy has an important effect in astroglial metabolism, decreasing glucose transport and metabolism and increasing the relative contribution of glial oxidative metabolism to the support of glutamatergic and GABAergic neurotransmissions. Copyright © 2003 John Wiley & Sons, Ltd. [source]


Developmental vitamin D deficiency alters brain protein expression in the adult rat: Implications for neuropsychiatric disorders

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2007
Lionel Almeras
Abstract An increased risk for multiple sclerosis and schizophrenia is observed at increasing latitude and in patients born in winter or spring. To explore a possible link between maternal vitamin D deficiency and these brain disorders, we examined the impact of prenatal hypovitaminosis D on protein expression in the adult rat brain. Vitamin D-deficient female rats were mated with vitamin D normal males. Pregnant females were kept vitamin D-deficient until birth whereupon they were returned to a control diet. At week 10, protein expression in the progeny's prefrontal cortex and hippocampus was compared with control animals using silver staining 2-D gels associated with MS and newly devised data mining software. Developmental vitamin D (DVD) deficiency caused a dysregulation of 36 brain proteins involved in several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, PTMs, synaptic plasticity and neurotransmission. A computational analysis of these data revealed that (i) nearly half of the molecules dysregulated in our animal model have also been shown to be misexpressed in either schizophrenia and/or multiple sclerosis and (ii) an impaired synaptic network may be a consequence of mitochondrial dysfunction. [source]


Differential expression of p120 catenin in glial cells of the adult rat brain

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2004
Norbert Chauvet
Abstract p120 catenin (p120ctn) is involved in the regulation of cadherin-mediated adhesion and the dynamic organization of the actin cytoskeleton by modulating RhoGTPase activity. We have previously described the distribution of p120ctn during rat brain development and provided substantial evidence for the potential involvement of p120ctn in morphogenetic events and plasticity in the central nervous system. Here, we analyzed the cellular and ultrastructural distribution of p120ctn in glial cells of the adult rat forebrain. The highest intensity of immunostaining for p120ctn was found in cells of the choroid plexus and ependyma and was mainly restricted to the plasma membrane. However, p120ctn was almost absent from astrocytes. In contrast, in tanycytes, a particular glial cell exhibiting remarkable morphological plasticity, p120ctn, was localized at the plasma membrane and also in the cytoplasm. We show that a large subpopulation of oligodendrocytes expressed multiple isoforms, whereas other neural cells predominantly expressed isoform 1, and that p120ctn immunoreactivity was distributed through the cytoplasm and at certain portions of the plasma membrane. Finally, p120ctn was expressed by a small population of cortical NG2-expressing cells, whereas it was expressed by a large population of these cells in the white matter. However, in both regions, proliferating NG2-positive cells consistently expressed p120ctn. The expression of p120ctn by cells of the oligodendrocyte lineage suggests that p120ctn may participate in oligodendrogenesis and myelination. Moreover, the expression of p120ctn by various cell types and its differential subcellular distribution strongly suggest that p120ctn may serve multiple functions in the central nervous system. J. Comp. Neurol. 479:15,29, 2004. © 2004 Wiley-Liss, Inc. [source]


Impaired Energy Metabolism after Co-Exposure to Leadand Ethanol

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2005
Suresh Kumar Verma
One such factor, ethanol, might affect the neurotoxicity of lead by regulating its absorption and distribution. However, there is little information regarding the possible biochemical mechanism by which ethanol might be affecting the state of neuronal functions in lead-exposed individuals. Therefore, the present investigation involved the effect of alcohol (3 g/kg body weight, intragastrically, for 8 weeks) on lead-induced (50 mg/kg body weight, intragastrically, for 8 weeks) mitochondrial dysfunction in adult rat brain. Ethanol was found to enhance the toxic effects of lead in terms of decreased cellular energy reserves (ATP levels). Co-exposure to lead and ethanol caused marked decline in the rate of mitochondrial respiration as compared to lead alone. Further the activies of various components of the electron transport chain, viz. NADH dehydrogenase, succinate dehydrogenase and cytochrome oxidase depicted a significant decrease in the lead and ethanol co-exposed rats as compared to the lead-treated group. The results of the present study reflect that ethanol makes adult rat brain more vulnerable to the neurotoxic effects of lead in terms of altered mitochondrial energy metabolism. [source]


PRECLINICAL STUDY: Different effects of chronic phencyclidine on brain-derived neurotrophic factor in neonatal and adult rat brains

ADDICTION BIOLOGY, Issue 2 2006
Jun'ichi Semba
ABSTRACT The N-methyl-D-aspartate (NMDA) receptor and brain-derived neurotrophic factor (BDNF) are both known to play major roles in the normal development of the brain. We have hypothesized that the chronic blockade of NMDA with phencyclidine (PCP) may have a different effect on BDNF synthesis at different stages of development. In an acute experiment, rat pups and adult rats were injected with PCP (2.5, 5 or 10 mg/kg) at postnatal day (PD) 15 or 49, respectively. In a chronic experiment, rat pups were injected daily from PD 5 to PD 14 with PCP (2.5, 5 or 10 mg/kg), while adult rats were injected daily with the same dose from PD 39 to PD 48. BDNF levels in the hippocampus, striatum and frontal cortex were determined by ELISA assay 24 hours after the last injection. Chronic PCP treatment of neonatal rats induced a dose-dependent decrease in BDNF in the hippocampus but not in the frontal cortex and striatum. Single injection of PCP to rat pups showed a slight reduction of BDNF in the hippocampus but only at higher doses. In contrast to neonatal brain, neither acute nor chronic injection of PCP influenced BDNF in adult brain. These findings suggest that chronic blockade of NMDA receptor in the early neonatal period has an inhibitory effect on BDNF synthesis in the hippocampus and may impair normal neurodevelopment in rat pups. [source]


Intrauterine proximity to male fetuses affects the morphology of the sexually dimorphic nucleus of the preoptic area in the adult rat brain

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2006
Minjuan Pei
Abstract Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17,-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17,-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains. [source]


Chlorotoxin-sensitive Ca2+ -activated Cl, channel in type R2 reactive astrocytes from adult rat brain

GLIA, Issue 4 2003
Stanislava Dalton
Abstract Astrocytes express four types of Cl, or anion channels, but Ca2+ -activated Cl, (ClCa) channels have not been described. We studied Cl, channels in a morphologically distinct subpopulation (, 5% of cells) of small (10,12 ,m, 11.8 ± 0.6 pF), phase-dark, GFAP-positive native reactive astrocytes (NRAs) freshly isolated from injured adult rat brains. Their resting potential, ,57.1 ± 4.0 mV, polarized to ,72.7 ± 4.5 mV with BAPTA-AM, an intracellular Ca2+ chelator, and depolarized to ,30.7 ± 6.1 mV with thapsigargin, which mobilizes Ca2+ from intracellular stores. With nystatin-perforated patch clamp, thapsigargin activated a current that reversed near the Cl, reversal potential, which was blocked by Cl, channel blockers, 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and Zn2+, by I, (10 mM), and by chlorotoxin (EC50 = 47 nM). With conventional whole-cell clamp, NPPB- and Zn2+ -sensitive currents became larger with increasing [Ca2+]i (10, 150, 300 nM). Single-channel recordings of inside-out patches confirmed Ca2+ sensitivity of the channel and showed open-state conductances of 40, 80, 130, and 180 pS, and outside-out patches confirmed sensitivity to chlorotoxin. In primary culture, small phase-dark NRAs developed into small GFAP-positive bipolar cells with chlorotoxin-sensitive ClCa channels. Imaging with biotinylated chlorotoxin confirmed the presence of label in GFAP-positive cells from regions of brain injury, but not from uninjured brain. Chlorotoxin-tagged cells isolated by flow cytometry and cultured up to two passages exhibit positive labeling for GFAP and vimentin, but not for prolyl 4-hydroxylase (fibroblast), A2B5 (O2A progenitor), or OX-42 (microglia). Expression of a novel chlorotoxin-sensitive ClCa channel in a morphologically distinct subpopulation of NRAs distinguishes these cells as a new subtype of reactive astrocyte. GLIA 42:325,339, 2003. © 2003 Wiley-Liss, Inc. [source]


Molecular and cellular mechanisms of neuroprotection by vascular endothelial growth factor

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 1-2 2005
Feng-Yan Sun
Abstract The present view of the neuroprotective functions and mechanisms of action of vascular endothelial growth factor (VEGF) is based on studies of neuronal ischemic/hypoxic models in vivo and in vitro. Endogenous neuronal VEGF increases in the ischemic brain and plays a neuroprotective role in the pathophysiologic processes that follow stroke. Exogenous VEGF, directly administered or overexpressed by gene delivery into rat brains, reduces ischemic brain infarct and decreases hypoxic neuronal death. The main neuroprotective mechanisms of VEGF include: (1) modulation of the phosphatidylinositol 3,-kinase (PI3K)/Akt/nuclear factor-,B signaling pathway, inhibition of caspase-3 activity, and reduction of ischemic neuronal apoptosis; (2) inhibition of outward delayed rectifier potassium channel currents and increase of ischemia-induced tyrosine phosphorylation of Kv1.2 potassium channel proteins via activation of the PI3K pathway; and (3) enhancement of proliferation and migration of neural progenitors in the subventricular zone and improvement of striatal neurogenesis and maturation of newborn neurons in adult rat brains after stroke. © 2004 Wiley-Liss, Inc. [source]