Association of refractory complex partial seizures with a polymorphism of ApoE genotype

Apolipoprotein E (ApoE) is a constituent of many types of lipoproteins that play a role in metabolism of cholesterol and lipids in the body as well as in the brain. ApoE is synthesised in astrocytes and microglia and enter to neurons through LDL, LRP and VLDL receptors. Recently it was shown that ApoE is also produced in neurons. ApoE has a role in modulating learning and memory, structural plasticity, mobilization of cholesterol in repair, growth and maintenance of myelin and neuronal membranes during development and aging, and cell death after ischemic, convulsive, or other type of brain injury. The aim of this research was to investigate the possible association of ApoE gene polymorphism with the development of resistance to pharmacological therapy in patients with partial complex seizures with or without secondary generalization. In this prospective matched-pair controlled study, 60 patients with cryptogenic epilepsy with complex partial seizures, with or without secondary generalization, who have been suffering for five or more years, were studied. The first group comprised 30 patients refractory to the current therapy, while the second group consisted of patients with well-controlled seizures. The refractory and non-refractory groups of patients differed significantly in their phenotypes. Phenotype E3/4 was six times more frequent in refractory group than among non-refractory group. The lack of response was shown to be significantly associated with the presence of epsilon4 allele. This study provided evidence that the presence of epsilon4 allele is more often associated with a lack of response to current antiepileptic drugs as compared to epsilon2 and epsilon3 alleles.     

Do glia contribute to behaviour? A neuromodulatory review

1. The links between behavioural state, gross electrophysiology and the activity of neurons and astrocytes are reviewed to stimulate interest in the contributions that glia make to behaviour. 2. Behavioural arousal in which neuronal responsivity ("sensitivity") is elevated is also associated with a sustained (0.5-10 sec) potential shift (SPS). 3. There is powerful and accumulating evidence that the SPS is primarily of glial origin. 4. In epilepsy neurons are hyperactive and there is a massive SPS during seizures. In seizure free periods, epileptic animals frequently have elevated arousal responses and increased neuronal sensitivity, indicating that seizures may be due to elevation of the activity of a normally adaptive sensitizing mechanism. 5. The common finding of an astrocytic pathology in epilepsy and the links between arousal, neuronal sensitization, SPSs and seizures implicates a modulatory role for astrocytes in both health and disease. 6. Glia, especially astrocytes, may modulate neuronal responsiveness by regulation of the microenvironment. 7. At the current state of knowledge, regulation of extracellular ionic K+, Ca2+ and neurotransmitter glutamate and GABA seem to be the most important candidates for modulating neuronal sensitivity in arousal and abnormally for seizure genesis. 8. Both in phylogeny and in ontogeny, glia and neurons have intimate associations. 9. The functional astrocytic syncitium is in a prime position to control the ecology of neuronal populations and thereby their activity. 10. The physiology and biochemistry of glia-neuronal interactions offers exciting new prospects for developments in behavioural neuroscience.     

Immunohistochemical localization of P-glycoprotein in rat brain and detection of its increased expression by seizures are sensitive to fixation and staining variables.

The MDR1 gene product, P-glycoprotein (P-gp), was shown to confer multidrug resistance to cancer cells, but its overexpression is also suggested to be involved in pharmacoresistance of epilepsy by acting as an energy-dependent drug-efflux pump in the blood-brain barrier (BBB). In normal brain tissue, P-gp is almost exclusively expressed by capillary endothelial cells (EC) of the BBB, whereas little or no expression is detected in other cell types. Increased P-gp expression was observed after seizures, but localization of this increase, i.e., within brain capillary EC or within parenchymal or perivascular astrocytes, which contribute to the BBB function, is controversial. To test whether these antithetic data arise from unusual properties of the antigen itself, we compared different immunohistochemical techniques and monoclonal or polyclonal antibodies to P-gp in normal rat brain and rat brain after kainate-induced seizures. Using acetone-fixed cryostat sections of snap-frozen tissue, strong P-gp labeling was detected in EC and, after seizures, in hippocampal neurons, but not in astrocytes. In contrast, EC and neuronal P-gp immunolabeling were not seen in paraformaldehyde-fixed sections, whereas both perivascular and parenchymal astrocytes exhibited strong P-gp labeling after seizures. The lack of P-gp labeling in EC by paraformaldehyde fixation, was reversed by treatment of the sections with acetate/ethanol. These experiments demonstrate that various fixation conditions have a striking effect on the immunohistochemical localization of P-gp in rat brain and detection of its increased expression by seizures. When data obtained from different immunohistochemical techniques are taken together, seizures seem to induce overexpression of P-gp in four different cell types, i.e., EC, perivascular astrocytes, parenchymal astrocytes, and neurons.     

Dietary supplementation with α-tocopherol reduces neuroinflammation and neuronal degeneration in the rat brain after kainic acid-induced status epilepticus

Abstract

Vitamin E (as α-tocopherol, α-T) is proposed to alleviate glia-mediated inflammation in neurological diseases, but such a role in epilepsy is still elusive. This study investigated the effect of α-T supplementation on glial activation, neuronal cell death and oxidative stress of rat brain exposed to kainate-induced seizures. Animals were fed for 2 weeks with a α-T-enriched diet (estimated intake of 750 mg/kg/day) before undergoing status epilepticus. Compliance to supplementation was demonstrated by the remarkable increase in brain α-T. Four days after seizure, brain α-T returned to baseline and lipid peroxidation markers decreased as compared to non-supplemented rats. Status epilepticus induced a lower up-regulation of astrocytic and microglial antigens (GFAP and MHC II, respectively) and production of pro-inflammatory cytokines (IL-1β and TNF-α) in supplemented than in non-supplemented animals. This anti-inflammatory effect was associated with a lower neuronal cell death. In conclusion, α-T dietary supplementation prevents oxidative stress, neuroglial over-activation and cell death occurring after kainate-induced seizures. This evidence paves the way to an anti-inflammatory and neuroprotective role of α-T interventions in epilepsy.     

In vivo activated brain astrocytes may produce and secrete nerve growth factor-like molecules.

The cellular localization of the nerve growth factor-like immunoreactivity (NGF-LIR) has been studied in the septum and hippocampus of the rat brain 7 days following partial electrolytic lesion (2 mA, 30 s) of the septohippocampal pathways or after single intraventricular administration of 15 U of interleukin-1 beta (IL-1 beta). A double immunostaining technique which allowed a simultaneous localization of NGF-LIR and that of astroglia marker glial fibrillary acidic protein was used. Our data show that after both treatments, apart from neuronal localization of NGF-LIR typical for normal brain, many astrocytes both in the septum and hippocampus became NGF-like immunoreactive. Besides, NGF-LIR often formed a "halo" reaction around astrocytes. These results support the notion that activated in vivo brain astrocytes may, just as astrocytes growing in vitro, synthesize and secrete NGF-like molecules. Our findings may be of importance in considerations concerning trophic support to the cholinergic neurons of the basal forebrain nuclei whose impaired function is essentially responsible for some cognitive deficits in neurodegenerative diseases such as Alzheimer disease.     

Aortic coarctation hypertension induces fibroblast growth factor-2 immunoreactivity in the stimulated nucleus tractus solitarii

The actions of neurotrophic factors i.e. basic fibroblast growth factor (bFGF, FGF-2) to neurons are related not only to neuronal development and maintenance but also to synaptic plasticity regarding neurotransmission. We analyzed here the levels of FGF-2 immunoreactivity in the nucleus tractus solitarii (NTS) of Wistar Kyoto rats in response to alterations of neuronal activity promoted by the stimulation of the baroreceptor reflex following an aortic coarctation-induced-hypertension. The FGF-2 immunoreactivity (IR) was found in the cytoplasm of the neurons and in the nuclei of the glial cells in the NTS. A large number of NTS neurons expressed FOS immunoreactivity 4 h after coarctation, as an indication of neuronal activity. Stereological methods showed an increased number of FGF-2 immunoreactive (ir) neuronal profiles (90%) and glial profiles (149%) in the NTS of the 72 h aortic coarctated rats. 1-week later, FGF-2 ir neurons were still increased (54%) but no change was found in the number of FGF-2 ir glial profiles. The double immunoperoxidase method revealed that the majority of the FGF-2 ir glial cells was glial fibrillary acidic protein (GFAP) positive astrocytes. GFAP immunohistochemistry showed an astroglial reaction at 72 h time-interval (55%) but not 1 week after stimulation. The number of the cresyl violet positive neurons and OX42 ir profiles (marker of activated microglia) in the NTS of coarctated rats were not different from control by 1 week and 1 month after the surgery, indicating a lack of NTS injury in this period following coarctation hypertension. FGF-2 may be an important neurotrophic factor in areas involved in the control of blood pressure. The increased FGF-2 IR in the NTS cells following neuronal stimulation may represent trophic and plastic adaptive responses in this nucleus in an autocrine/paracrine fashion.     

Role of calpain in spinal cord injury: Increased calpain immunoreactivity in rat spinal cord after impact trauma

Impact spinal cord injury (20 g-cm) was induced in rat by weight drop. The immunoreactivity of mcalpain was examined in the lesion and adjacent areas of the cord following trauma. Increased calpain immunoreactivity was evident in the lesion compared to control and the immunostaining intensity progressively increased after injury. The calpain immunoreactivity was also increased in tissue adjacent to the lesion. mCalpain immunoreactivity was significantly stronger in glial and endothelial cells, motor neurons and nerve fibers in the lesion. The calpain immunoreactivity also increased in astrocytes and microglial cells in the adjacent areas. Proliferation of microglia and astrocytes identified by GSA histochemical staining and GFAP immunostaining, respectively, was seen at one and three days after injury. Many motor neurons in the ventral horn showed increased calpain immunoreactivity and were shrunken in the lesion. These studies indicate a pivotal role for calpain and the involvement of glial cells in the tissue destruction in spinal cord injury. Special issue dedicated to Dr. Marion E. Smith.     

Do astrocytes contribute to excitation underlying seizures?

Synchronous neuronal activity during seizures is thought to arise from an entirely neuronal origin. A recent study by Tian et al. suggests that by releasing glutamate, astrocytes contribute to the neuronal depolarizations underling epilepsy. Treatment of hippocampal and cortical tissue with compounds that induce seizures was shown to excite astrocytes directly through a pathway that stimulates the release of glial glutamate. Anticonvulsants reduce the activity of this non-neuronal pathway, suggesting that there is an astrocytic basis for epilepsy. Should further experimental analysis corroborate and extend this conclusion, this pathway will be a novel target for therapeutic intervention.     

蝎毒对癫痫敏感性和海马GFAP释放的影响

目的和方法 :本工作用海人酸癫痫模型 ,通过对癫痫大鼠蝎毒治疗后行为变化及脑内胶质原纤维酸性蛋白(GFAP)免疫反应活性的检测 ,对蝎毒抗癫痫反复发作的相关脑区及其机制做以初步探讨。结果 :癫痫大鼠蝎毒治疗三周后 ,能明显减少癫痫发作的例数 ,减轻癫痫发作的程度 ,使发作的潜伏期延长 (P <0 .0 5 )。免疫细胞化学的实验显示 ,蝎毒抗癫痫反复发作的相关脑区是海马。 8例蝎毒治疗的大鼠与实验对照组相比 ,有 6例背侧海马GFAP免疫染色明显减轻 ,未见星形胶质细胞增生 ;CA1区无明显神经元缺失 ;而且与空白对照组相比无显著差异。结论 :癫痫大鼠蝎毒治疗三周后 ,能明显减轻癫痫发作的行为 ,抑制海马星形胶质细胞的增生肥大 ,减轻海马神经元受损的程度。蝎毒抑制海马星形胶质细胞增生很可能是蝎毒抗癫痫反复发作的重要机制之一。     

Laminin and fibronectin in normal and malignant neuroectodermal cells

Laminin and fibronectin, the major noncollagenous matrix glycoproteins, were studied in connection with normal brain cells and neuroectodermal cell lines. Laminin, a Mr 900,000 dalton matrix glycoprotein and an essential component of basement membranes, was found to be produced by cultured cells of several malignant cell lines of neuroectodermal origin. In cultured mouse C1300 neuroblastoma line cells laminin was localized, by immunoelectron microscopy, to the rough endoplasmic reticulum and, to sites of cell-to-cell and cell-to-substratum adhesion. Further experiments on the intracellular transport of this glycoprotein in C1300 cells confirmed that laminin is, at least partially, transported through the Golgi pathway. These results favor a role for laminin in attachment and cellular interactions of malignant neuronal cells. Laminin was also found in connection with neurons and glial cells from mammalian brain. In primary cultures from developing rat brain the vast majority of non-neuronal cells (80%) expressed immunoreactivity for the glial fibrillary acidic protein, a cytoskeletal protein specific for astrocytes. During the first week in culture all the glial fibrillary acidic protein-positive cells, with the exception of mature-looking star-shaped astrocytes, exhibited immunoreactivity for laminin. The intracellular laminin disappeared gradually after a few weeks in culture, but an extensive laminin matrix persisted and seemed to be localized on the upper surface of the non-neuronal cells. The neurofilament-positive neurons were negative for laminin. Pretreatment of the cultures with the ionophore monensin, caused accumulation of laminin-immunoreactivity within the Golgi region, which confirmed that laminin is, indeed, produced by cultured astrocytes and secreted through the Golgi complex. No fibronectin immunoreactivity was found in the majority of glial cells. However, under culture conditions where fibronectin was omitted from the culture medium there was, in the primary cultures, a minor population of glial fibrillary acidic protein-positive flat glial cells that exhibited intracytoplasmic immunofluorescence for fibronectin. In the presence of fibronectin in culture medium no fibronectin-positive glial cells could be detected. It thus appears that laminin, and to a minor extent fibronectin, are proteins that normal glial cells are capable of producing under specific conditions. Laminin and fibronectin were localized in adult rat brain in capillary and meningeal structures.(ABSTRACT TRUNCATED AT 400 WORDS)     

Modification of Astrocyte Metabolism as an Approach to the Treatment of Epilepsy: Triheptanoin and Acetyl-<Emphasis Type="SmallCaps">l</Emphasis>-Carnitine

Epilepsy is a severe neurological disorder characterized by altered electrical activity in the brain. Important pathophysiological mechanisms include disturbed metabolism and homeostasis of major excitatory and inhibitory neurotransmitters, glutamate and GABA. Current drug treatments are largely aimed at decreasing neuronal excitability and thereby preventing the occurrence of seizures. However, many patients are refractory to treatment and side effects are frequent. Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults. In rodents, the pilocarpine-status epilepticus model reflects the pathology and chronic spontaneous seizures of TLE and the pentylenetetrazole kindling model exhibits chronic induced limbic seizures. Accumulating evidence from studies on TLE points to alterations in astrocytes and neurons as key metabolic changes. The present review describes interventions which alleviate these disturbances in astrocyte–neuronal interactions by supporting mitochondrial metabolism. The compounds discussed are the endogenous transport molecule acetyl-l-carnitine and the triglyceride of heptanoate, triheptanoin. Both provide acetyl moieties for oxidation in the tricarboxylic acid cycle whereas heptanoate is also provides propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis—the refilling of the tricarboxylic acid cycle.     

甘珀酸对内脏痛大鼠延髓星形胶质细胞和神经元反应的影响

目的:研究侧脑室注射甘珀酸后对福尔马林灌胃致内脏疼痛大鼠的延髓迷走孤束复合体内星形胶质细胞和神经元反应的影响.方法:经侧脑室注射缝隙连接阻断剂甘珀酸(carbenoxolone,CBX)后向大鼠胃内灌入2.5%福尔马林2ml诱发内脏疼痛,用免疫组织化学方法观察延髓迷走孤束复合体(VSC)内抗Fos蛋白(标记神经元)和抗胶质原纤维酸性蛋白(标记星形胶质细胞)的单一或双重标记的免疫荧光染色.结果:福尔马林灌胃后大鼠出现烦躁易激惹,呼吸变快,持续1h;而预先侧脑室注射CBX则动物疼痛行为学反应明显减轻.免疫组织化学染色发现福尔马林灌胃后大鼠VSC中的Fos免疫反应数目增强;大鼠预先侧脑室注射CBX后VSC中的Fos免疫反应数目明显减弱.结论:延髓VSC中的星形胶质细胞和神经元参与福尔马林灌胃致内脏痛的调节,星形胶质细胞可能通过缝隙连接影响神经元对内脏痛的调节功能.     

S100 immunoreactivity is increased in reactive astrocytes of the visual pathways following a mechanical lesion of the rat occipital cortex

After demonstration of the paracrine action of glial neurotrophic factors, gliosis has also been considered to be related to neuronal trophism and plasticity rather than solely a repair event following brain injury. S100 is a Ca2+ binding protein, present mainly in astrocytes, that exerts paracrine trophic effects on several neuronal populations. This study analyses the presence of S100 protein by means of immunohistochemistry combined with stereology in the reactive glial cells of the rat visual pathways following a lesion of the visual cortex. Adult male Wistar rats were submitted to a unilateral aspiration of the occipital cortex or to a sham operation. One week later the rats were killed and their brain processed for immunochemistry. Single antibody immunohistochemistry was performed for the visualization of glial fibrillary acidic protein (GFAP, a marker for astrocytes), OX-42 (a marker for microglia) and S100 protein. Double immunofluorescence procedures were applied for co-localization of the S100/GFAP and S100/OX-42. An optical dissector, point interceptors and rotators were used to quantify the degree of glial activation and the changes in the S100 immunoreactivity. We observed an intense microglial and astroglial reaction in addition to an increased S100 immunoreactivity in the occipital cerebral cortex, geniculate nucleus and hippocampus ipsilateral to the lesion. In the ipsilateral superior colliculus, an intense astroglial activation was accompanied by an up-regulation of S100 immunoreactivity. Double-immunofluoresence revealed an increased S100 immunoreactivity in reactive astrocytes, but not in the reactive microglia. Evidence has therefore been obtained that after mechanical trauma, the astroglial S100 protein participates in the trophism and plasticity of the injured visual pathways.     

Gabapentin Administration Reduces Reactive Gliosis and Neurodegeneration after Pilocarpine-Induced Status Epilepticus

The lithium-pilocarpine model of epilepsy reproduces in rodents several features of human temporal lobe epilepsy, by inducing an acute status epilepticus (SE) followed by a latency period. It has been proposed that the neuronal network reorganization that occurs during latency determines the subsequent appearance of spontaneous recurrent seizures. The aim of this study was to evaluate neuronal and glial responses during the latency period that follows SE. Given the potential role of astrocytes in the post-SE network reorganization, through the secretion of synaptogenic molecules such as thrombospondins, we also studied the effect of treatment with the α2δ1 thrombospondin receptor antagonist gabapentin. Adult male Wistar rats received 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once SE was achieved, seizures were stopped with 20 mg/kg diazepam. Animals then received 400 mg/kg/day gabapentin or saline for either 4 or 14 days. In vitro experiments were performed in dissociated mixed hippocampal cell culture exposed to glutamate, and subsequently treated with gabapentin or vehicle. During the latency period, the hippocampus and pyriform cortex of SE-animals presented a profuse reactive astrogliosis, with increased GFAP and nestin expression. Gliosis intensity was dependent on the Racine stage attained by the animals and peaked 15 days after SE. Microglia was also reactive after SE, and followed the same pattern. Neuronal degeneration was present in SE-animals, and also depended on the Racine stage and the SE duration. Polysialic-acid NCAM (PSA-NCAM) expression was increased in hippocampal CA-1 and dentate gyrus of SE-animals. Gabapentin treatment was able to reduce reactive gliosis, decrease neuronal loss and normalize PSA-NCAM staining in hippocampal CA-1. In vitro, gabapentin treatment partially prevented the dendritic loss and reactive gliosis caused by glutamate excitotoxicity. Our results show that gabapentin treatment during the latency period after SE protects neurons and normalizes PSA-NCAM probably by direct interaction with neurons and glia.     

Widespread immunoreactivity for neuronal nuclei in cultured human and rodent astrocytes

The monoclonal antibody (mAb) neuronal nuclei (NeuN) labels the nuclei of mature neurons in vivo in vertebrates. NeuN has also been used to define post-mitotic neurons or differentiating neuronal precursors in vitro . In this study, we demonstrate that the NeuN mAb labels the nuclei of astrocytes cultured from fetal and adult human, newborn rat, and embryonic mouse brain tissue. A non-neuronal fibroblast cell line (3T3) also displayed NeuN immunoreactivity. We confirmed that NeuN labels neurons but not astrocytes in sections of P10 rat brain. Western blot analysis of NeuN immunoreactive species revealed a distribution of bands in nucleus-enriched fractions derived from the different cell lines that was similar, but not identical to adult rat brain homogenates. We then examined the hypothesis that the glial fibrillary acidic protein/NeuN-double positive population of cells might correspond to neuronal precursors. Although the NeuN-positive astrocytes were proliferating, no evidence of neurogenesis was detected. Furthermore, expression of additional neuronal precursor markers was not detected. Our results indicate that primary astrocytes derived from mouse, rat, and human brain express NeuN. Our findings are consistent with NeuN being a selective marker of neurons in vivo , but indicate that studies utilizing NeuN-immunoreactivity as a definitive marker of post-mitotic neurons in vitro should be interpreted with caution.     

Aluminum affects glial system and behavior of rats

Aluminum (Al) has been associated with neuronal dysfunction. These neuronal changes may involve glial alterations. We intend to evaluate the consequence of Al on the glial system and the behavior of rats exposed chronically to 0.3% of aluminum chloride in drinking water during 4 months in adulthood (A) or since intra-uterine age (IU); animals from this latter group were sacrificed at four months of age. Our data show an intense glial fibrillary acidic protein (GFAP)-immunoreactivity with a high density of astrocytes in both treated groups compared with controls. However, in IU rats, astrocytes display prominent glial cell bodies and processes. A and IU rat groups perform a significantly reduced locomotor activity. However, using the dark/light box test, the IU rats prefer to spend more time in the enlightened compartment compared to other groups. Behavioral and glial changes caused by Al exposure bring support for the role of Al in brain dysfunction involving glial alterations.     

The effect of steroid treatment on lipocortin immunoreactivity of rat brain

Lipocortin-1, lipocortin-2 and lipocortin-5 were immunohistochemically assessed in rats. Apart from animals receiving no treatment, other animals received pretreatment with methylprednisolone, or the 21-aminosteroid U-74389F. Whereas Hpocortin immunoreactivity was absent in the greater part of the brain in animals not pretreated with steroid (except in sporadic microglial cells and choroid plexus), there was obvious immunostaining of parenchymatous elements in steroid pretreated animals. In the steroid pretreated animals lipocortin immunoreactivity of the brain tissue may indicate local formation of lipocortin under the influence of steroids that had entered the tissue. The cellular elements which showed immunostaining included meningeal cells, neurones, ependyma, oligodendroglia and capillary endotheHum.     

Dietary supplementation with α-tocopherol reduces neuroinflammation and neuronal degeneration in the rat brain after kainic acid-induced status epilepticus

Vitamin E (as α-tocopherol, α-T) is proposed to alleviate glia-mediated inflammation in neurological diseases, but such a role in epilepsy is still elusive. This study investigated the effect of α-T supplementation on glial activation, neuronal cell death and oxidative stress of rat brain exposed to kainate-induced seizures. Animals were fed for 2 weeks with a α-T-enriched diet (estimated intake of 750 mg/kg/day) before undergoing status epilepticus. Compliance to supplementation was demonstrated by the remarkable increase in brain α-T. Four days after seizure, brain α-T returned to baseline and lipid peroxidation markers decreased as compared to non-supplemented rats. Status epilepticus induced a lower up-regulation of astrocytic and microglial antigens (GFAP and MHC II, respectively) and production of pro-inflammatory cytokines (IL-1β and TNF-α) in supplemented than in non-supplemented animals. This anti-inflammatory effect was associated with a lower neuronal cell death. In conclusion, α-T dietary supplementation prevents oxidative stress, neuroglial over-activation and cell death occurring after kainate-induced seizures. This evidence paves the way to an anti-inflammatory and neuroprotective role of α-T interventions in epilepsy.     

载脂蛋白E与癫痫的关系

载脂蛋白E（apolipoprotein E,ApoE）在中枢神经系统修复受损细胞膜、轴索生长和突触形成的过程中起重要作用.研究证明,在外伤、中毒、免疫应答以及痫性放电引起的脑部损伤的病灶组织中都存在载脂蛋白E表达的上调现象.载脂蛋白E的基因多态性和表达量与难治性癫痫的发生和发展有一定的相关性,提示载脂蛋白E的异常可能是难治性癫痫产生机制中的一个重要环节.     

Alterations of Glial Cells in the Mouse Hippocampus During Postnatal Development

We investigated the postnatal alterations of neurons, astrocyte, oligodendrocyte, and microglia in the mouse hippocampal CA1 sector and dentate gyrus under the same conditions using immunohistochemistry. Neuronal nuclei (NeuN), Glial fibrillary acidic protein (GFAP), 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase), and ionized calcium binding adaptor molecule 1 (Iba 1) immunoreactivity were measured in 1-, 2-, 4-, and 8-week-old mice. Total number of NeuN-positive neurons was unchanged in the mouse hippocampal CA1 sector and dentate gyrus from 1 to 8 weeks of birth. In contrast, a significant increase in the number of GFAP-positive astrocytes was observed only in the hippocampal CA1 sector of 1-week-old mice when compared with 8-week-old animals. Thereafter, total number of GFAP-positive astrocytes was unchanged in the hippocampal CA1 sector and dentate gyrus from 2 to 8 weeks of birth. For microglia, a significant increase in the number of Iba 1-positive microglia was observed in the hippocampal CA1 sector and dentate gyrus of 1-, 2-, and 4-week-old mice as compared with 8-week-old animals. On the other hand, a significant decrease in the area of expression of CNPase-positive fibers was observed in the hippocampal CA1 sector of 1- and 2-week-old mice as compared with 8-week-old animals. In dentate gyrus, a significant decrease in the area of expression of CNPase-positive fibers was found in 1-, 2-, and 4-week-old mice. Furthermore, our double-labeled immunostaining showed that brain-derived neurotrophic factor (BDNF) immunoreactivity was observed in GFAP-positive astrocytes and Iba 1-positive microglia in the hippocampal CA1 sector and dentate gyrus of 1- and 2-week-old mice. These results show that glial cells may play some role in the maintenance and neuronal functions of hippocampal CA1 pyramidal neurons and granule cells of dentate gyrus during postnatal development. Furthermore, our results demonstrate that glial BDNF may play an important role in the maturation of oligodendrocyte in the hippocampal CA1 sector and dentate gyrus during postnatal development. Thus, our findings provide valuable information on the developmental processes.