Transient increase of NMDA-binding sites in human hippocampus during development

In the human hippocampus, the density of glutamate and N-methyl-D-aspartate (NMDA) binding sites follows during development a bell-shaped curve with a peak at 23-27 fetal weeks. We suggest that there is a transient increased density of NMDA binding sites during a restricted period of hippocampal development; this may play an important role in developmental plasticity.     

Caspase-3在出生后大鼠海马中的表达

目的 探讨Wistar大鼠海马生后发育过程中,活化的Caspase-3与凋亡之间的关系. 方法 应用免疫荧光方法观测活化的Caspase-3和赫斯特荧光染料33342(Hoechst 33342)在生后不同时期大鼠海马CA1、CA3区和齿状回(DG)中的表达情况. 结果 在CA1区,活化的Caspase-3的表达在生后7d(P7)达到高峰;在CA3区,P2达到高峰,然后逐渐减弱.在DG,P7后又有所增强,到P14达到高峰,并在所观测的其余时段维持此水平.观测的3个区的凋亡细胞数目都在P7达到高峰,然后逐渐减少. 结论 在大鼠海马生后发育过程中,活化的Caspase-3的表达存在特定的时空格局.活化的Caspase-3在CA1区与CA3区有丝分裂后期细胞和DG神经前体细胞中的作用和机制不同.     

大鼠海马γ-氨基丁酸-A受体在生后发育中的表达

目的:研究大鼠生后发育过程中海马组织γ-氨基丁酸-A(GABA-A)受体的表达规律。方法:用免疫组织化学和PCR技术,检测不同年龄大鼠海马组织GABA-A受体及编码该受体的mRNA表达,并用图像分析方法进行定量研究。结果:大鼠海马组织在生后3 d已经出现GABA-A受体免疫反应,以后逐渐增强,到生后30 d达到最高值,海马各区GABA-A受体免疫反应强度没有显著的差别;编码GABA-A受体的mRNA表达也有类似的增龄性增多,但其表达高峰值提前到14 d。结论:生后大鼠海马GABA-A受体表达在一定时期内呈增龄性表达增强的趋势。     

点燃模型大鼠海马和皮层星形胶质细胞变化的动态观察

目的　探讨星形胶质细胞在戊四唑 (PTZ)化学点燃模型癫痫发病中的作用。方法　用 30只Wistar大鼠随机分为对照组和模型组。采用免疫组织化学方法和图像分析技术 ,对PTZ点燃各发作级别大鼠海马结构和颞叶皮质部位的胶质纤维酸性蛋白 (GFAP)的变化作动态观察。结果　GFAP值改变见于点燃后Ⅲ级组开始增加 ,Ⅴ级组达到高峰 ,Ⅴ级后 2 4h组仍有持续增加。结论　戊四唑点燃癫痫模型中 ,随着点燃级别的进展 ,GFAP免疫表达逐渐增加。提示星形胶质细胞GFAP含量的增加可能是PTZ点燃模型癫痫发病的原因之一。     

Protein turnover in brain during the development of alcohol dependence

The chronic effect of ethanol on central nervous system protein turnover was investigated in selected regions of brain following intoxication and withdrawal in a strain of ethanol preferring mice.Mice were serially injected with [¹⁴C]glucose in order to achieve a constant specific radioactivity of brain glutamase. Protein turnover was calculated from the specific activities of extracted protein and free glutamate.Results from these studies show that ethanol causes a significant increase in protein turnover in all sections of brain. The brain protein turnover in animals following alcohol withdrawal also shows an increase which deviates significantly from controls in 2 of the 3 regions examined.     

Questioning the depolarizing effects of GABA during early brain development

During early brain development, γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the adult brain, has been thought to be an important source of excitatory neurotransmission. This view, however, was recently challenged by a series of studies that claim that the excitatory effect of GABA is due to non-physiological in vitro experimental conditions. In this article, we aim to summarize results that support and challenge the traditional point of view, and indicate some strong and weak points of both positions.     

Human brain synapses during early prenatal development

Laboratory of Development of the Human Nervous System, Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 105, No. 3, pp. 357–359, March, 1988.     

Energy metabolism in mammalian brain during development

Production of energy for the maintenance of ionic disequilibria necessary for generation and transmission of nerve impulses is one of the primary functions of the brain. This review attempts to link the plethora of information on the maturation of the central nervous system with the ontogeny of ATP metabolism, placing special emphasis on variations that occur during development in different brain regions and across the mammalian species. It correlates morphological events and markers with biochemical changes in activities of enzymes and pathways that participate in the production of ATP. The paper also evaluates alterations in energy levels as a function of age and, based on the tenet that ATP synthesis and utilization cannot be considered in isolation, investigates maturational profiles of the key processes that utilize energy. Finally, an attempt is made to assess the relevance of currently available animal models to improvement of our understanding of the etiopathology of various disease states in the human infant. This is deemed essential for the development and testing of novel strategies for prevention and treatment of several severe neurological deficits.     

Variations in trace metal levels in rat hippocampus during ontogenetic development

The variations in trace metal (zinc, iron, copper and manganese) levels in rat hippocampus were followed by atomic absorption spectrophotometry from the 17th embryonic day to the 100th postnatal day. In agreement with histochemical observations, it was found that the greatest relative increase in the hippocampal zinc level occurs during the 11th-20th postnatal days, simultaneously with the morphological maturation of the mossy fibre terminals. The iron level falls dramatically from the 17th embryonic day to the 3rd postnatal day. Beginning from the 11th postnatal day, the iron level, similarly to the copper level, continuously increases with age. The manganese level rises up to the 20th postnatal day, and subsequently progressively decreases. It is suggested that all of these elements are indispensable for the normal development and functioning of the hippocampus and the mossy fibre terminals.     

Naturally occurring cell death in the subicular complex and hippocampus in the rat during development

Cell death in the subicular complex and hippocampus occurs from P0 to P7 in the rat. Dead cells first appear in the subcortical and subammonic plates, and predominate in the border region between the main regional subfields. Cell death in the cellular layers predominates in the subicular complex. CA1 and intermediate region between CA1 and CA3. Dead cells are almost absent in the upper plexiform layers and dentate gyrus.     

Localization of CD226 in the mouse hippocampus and cerebellum during adulthood and postnatal development

CD226, a member of cell adhesion molecules, has been widely studied in the immune system; however, its expression in the CNS remains unknown. In our present study, we detected CD226 mRNA and protein in the mouse hippocampus and cerebellum by RT-PCR and Western blotting, respectively. Immunohistochemical studies found that CD226 is primarily located in the hilus of the dentate gyrus and stratum lucidum aligned along the pyramidal cells in the hippocampal CA3 area, the interspaces of granular cells and the somata of the Purkinje cells in the cerebellar cortex during adulthood. Double-staining results revealed that CD226 co-localized well with synaptic marker proteins including synaptophysin, syntaxin and PSD-95. During postnatal development, CD226 could not be detected at its adult locations until postnatal day 12; however, it was temporally expressed in the somata of neighboring or distant nuclei associated with its adult location. These results showed the diverse localization of CD226 in the mouse hippocampus and cerebellum for the first time and suggested its potential role in the CNS.     

High-affinity glutamine uptake of the rat hippocampus during postnatal development: a quantitative autoradiographic study

Glutamine uptake into hippocampal slices of the rat was investigated autoradiographically. The characteristics of registered [14C]glutamine uptake such as the incubation with the radiolabelled amino acid at a concentration of 3.5 mumol/l, sodium dependency, the distribution pattern of radioactive material, and the postnatal development of uptake capacity are comparable with those of high-affinity uptake of glutamate. Densitometric evaluation of grain density over hippocampal layers exhibited a marked enhancement of uptake capacity in the neuropil areas during the first postnatal weeks. In the strata oriens and radiatum (CA1) radiolabelling increased from day 2 to 25 by about 390 and 410%, in the strata oriens and lacunosum-moleculare of CA3 by about 350 and 375%, respectively. In contrast, the rise in the accumulation rate in cell body layers was negligible. The temporal and topographical profiles of glutamine uptake in the hippocampal neuropil correlated with those of the activity of phosphate-activated glutaminase and parameters of maturation of the glutamatergic transmission system which have fairly similar time characteristics, suggesting a mutually causative relationship of all these factors.     

Aquaporin7 expression during perinatal development of mouse brain

Emerging evidence suggests that brain aquaporins (AQPs) play important roles in the dynamic regulation of brain water homeostasis and the production of cerebrospinal fluid (CSF) under normal, as well as pathological, conditions. To date, the spatiotemporal expression patterns of AQP1, 4, and 9 have been elucidated in brain tissues. However, the expression of AQP7, an aquaglyceroporin associated with brain development, has not been shown. In the present study, we examined expression of AQP7 during perinatal and adult brain development in the mouse. Throughout brain development, the immunoreactivity of AQP7 was largely found in the choroid plexus (CP). AQP7 immunoreactivity in ependyma (Ep), pia, and blood vessels (BV) was increased during perinatal to postnatal development. Cells in the different layers of cerebral cortex became a little positive for AQP7 immunoreactivity during postnatal development. Optimized semi-quantitative RT-PCR and Western blot analysis revealed that AQP7 mRNA and protein levels increased during perinatal development of brain. To our knowledge, this is the first report on the pattern of AQP7 expression in brain tissues. These results suggest that AQP7 is an important structural element in the choroid plexus and is possibly involved in the production of CSF during brain development in mice.     

Consequences of recurrent seizures during early brain development.

It is well documented that prolonged seizures (status epilepticus) can cause neuronal injury and result in synaptic reorganization in certain brain regions. However, the effect of recurrent, relatively short seizures in young animals on subsequent brain development is not known. To study the consequences of recurrent seizures on the developing brain, we subjected immature rats to a total of 50 flurothyl-induced seizures from postnatal day 11 until day 23. Immunohistochemistry for c-fos was performed to characterize the pattern of neuronal activation following the seizures. Cell counting of dentate granule cells, CA3, CA1, and hilar neurons, using unbiased stereological methods, and the silver impregnation method were used to evaluate neuronal death following the recurrent seizures. Timm and Golgi staining were performed four weeks after the 50th seizure to evaluate the effects of recurrent seizures on synaptic organization. Our results show that recurrent flurothyl-induced seizures progressively increased excitability of the brain, as revealed by a dramatic increase in the extent and intensity of c-fos immunostaining. While no cell loss was detected in the hippocampus with either Cresyl Violet or silver stains, animals experiencing multiple daily seizures developed increased mossy fiber sprouting in both the supragranular layer of the dentate gyrus and the infrapyramidale layer of the CA3 region. Golgi staining confirmed that there was an increase in mossy fibers in the pyramidal cell layer. Our results suggest that serial recurrent seizures in the immature brain can lead to significant changes in mossy fiber distribution even though the seizures do not cause significant hippocampal cell loss.