Immunohistochemical changes related to ageing in the mouse hippocampus and subventricular zone

We investigated mainly immunohistochemical changes of nestin (a marker of neuroepithelial stem cells) and Ki-67 (a marker of proliferating cells) proteins related to ageing in the mouse hippocampus and subventricular zone (SVZ) using young adult (8 weeks old) and middle-aged (40 weeks old) mice. In the present study, no significant changes in neurons and astrocytes of the hippocampal CA1 sector were found in a middle-aged male ICR mice without severe senile weakness, as compared with young adult animals. In contrast, a significant change in the number of microglia was found in the hippocampal CA1 sector of the middle-aged mice. Furthermore, no significant changes in the number of nestin- and Ki-67-positive cells were observed in the hippocampal CA1 sector of the middle-aged mice. On the other hand, decreases in the number of nestin- and Ki-67-immunopositive cells were observed in the SVZ of the middle-aged mice. Furthermore, a migration of nestin- and Ki-67-immunoreactive cells in the corpus callosum was not observed in the SVZ of the middle-aged mice. In the dentate gyrus, significant decreases in the number of Ki-67-immunopositive cells were observed in the middle-aged mice. Our study also showed that nestin immunoreactivity was observed in both Ki-67-postive cells and astrocytes in the SVZ of young adult mice. These findings emphasize the need to recognize ageing as important factors in studies of microglia, which may help to clarify the role of glial cell structure and function during ageing processes. Furthermore, the present findings suggest that ageing processes may decrease neurogenesis in the corpus callosum, SVZ and dentate gyrus. Thus our present findings provide valuable information for the neurogenesis during ageing processes.     

Ischemia induces cell proliferation and neurogenesis in the gerbil hippocampus in response to neuronal death

We studied hippocampal cellular proliferation and neurogenesis processes in a model of transient global cerebral ischemia in gerbils by labelling dividing cells with 5'-Bromo-2'-deoxyuridine (BrdU). Surrounding the region of selective neuronal death (CA1 pyramidal layer of the hippocampus), an important increase in reactive astrocytes and BrdU-labelled cells was detected 5 days after ischemia. A similar result was found in the dentate gyrus (DG) 12 days after ischemia. The differentiation of the BrdU+ cells was investigated 28 days after BrdU administration by analyzing the morphology, anatomic localization and cell phenotype by triple fluorescent labelling (BrdU, adult neural marker NeuN and DNA marker TOPRO-3) using confocal laser-scanning microscopy. This analysis showed increased neurogenesis in the DG in case of ischemia and triple positive labelling in some newborn cells in CA1. Seven brain hemispheres from gerbils subjected to ischemia did not develop CA1 neuronal death; hippocampus from these hemispheres did not show any of the above mentioned findings. Our results indicate that ischemia triggers proliferation in CA1 and neurogenesis in the DG in response to CA1 pyramidal neuronal death, independently of the reduced cerebral blood flow or the cell migration from subventricular zone (SVZ).     

Wnt expression in the adult rat subventricular zone after stroke

Neurogenesis occurs in adult brain neural progenitor cells (NPCs) located in the subventricular zone (SVZ) of the lateral ventricle and the subgrandular zone of the hippocampal dentate gyrus. After ischemic stroke, NPCs in the SVZ proliferate and migrate towards the ischemic boundary region to replenish damaged neurons. During development, the Wnt pathways contribute to stem cell maintenance and promote neurogenesis. We hypothesized that stroke up regulates Wnt family genes in SVZ cells. Non-ischemic and ischemic cultured SVZ cells and a single population of non-ischemic and ischemic SVZ cells isolated by laser capture microdissection (LCM) were analyzed for Wnt pathway expression using real-time RT-PCR and immunostaining. The number of neurospheres increased significantly (p<0.05) in SVZ cells derived from ischemic (32+/-4.7/rat) compared with the number in non-ischemic SVZ cells (18+/-3/rat). Wnt family gene mRNA levels were detected in SVZ cells isolated from both cultured and LCM SVZ cells, however there was no up regulation between non-ischemic and ischemic SVZ cells. Immunostaining on brain sections also demonstrated no up regulation of Wnt pathway protein between ischemic and non-ischemic SVZ cells. Expression of the Wnt family genes in SVZ cells support the hypothesis that the Wnt pathway may be involved in neurogenesis in the adult brain. However, ischemia does not up regulate Wnt family gene expression.     

胚胎时期大鼠海马结构的发育

为研究胚胎时期大鼠海马结构的发育状况,用浸泡固定、石蜡切片、混合尼氏染色方法,观察了Ｅ１４、Ｅ１６、Ｅ１８、Ｅ２２天大鼠胚胎海马结构的发育过程。结果：Ｅ１４天基本上能区分出海马原基。Ｅ１６天海马原基背侧与下托部神经上皮延续,腹侧与隔区神经上皮及脉络丛基质相连续;此时海马原基可区分出３部分,即背侧的阿蒙角神经上皮,其下的原始齿状回神经上皮,腹侧的伞部胶质上皮。Ｅ１８天海马裂形成,将阿蒙角神经上皮与齿状回生发基质区分开来;ＣＡ１区锥体层和海马伞开始出现,齿状回外臂和门也开始形成并第一次见向齿状回迁移的细胞。Ｅ２２天海马裂消失,阿蒙角分子层与齿状回分子层贴在一起;ＣＡ１区锥体层增厚,ＣＡ３区锥体层出现并穿透门区;阿蒙角神经上皮变成单层结构,中间层变薄,仍见大量逗留的锥体细胞,海马槽形成;齿状回外臂轮廓出现,颗粒细胞呈单层排列,内臂起始部开始形成;ＣＡ３区中间层周围及个部附近见大量的细胞正朝门区迁移。研究表明：出生前阿蒙角ＣＡ１、ＣＡ３区锥体层已经形成,齿状回外臂的轮廓已形成,内臂刚开始出现,其轮廓将于出生后形成。     

Expression of the group I metabotropic glutamate receptor in the hippocampus of patients with mesial temporal lobe epilepsy

Immunocytochemical studies at light and electron microscopic levels in hippocampi of patients with mesial temporal lobe epilepsy showed mGluR1 and mGluR5 immunoreactivity in the molecular layer of the dentate gyrus and CA1 area, especially at the border between stratum oriens and alveus. By electron microscopy, degenerating neuronal elements were found in all areas studied. There were glial filamentous tangles which appeared similar to intranuclear inclusions in astrocytes in all areas studied. Reactive product for mGluR1 was localised only in post-synaptic elements. However, mGluR5 immunoreactivity was demonstrated in both post- and pre-synaptic elements in the molecular layer of the dentate gyrus and CA1 area. Reactive product for mGluR5 was also demonstrated in astrocytes and in the periphery of fibrillary tangles. We postulate that in patients with mesial temporal lobe epilepsy, mGluR1 may increase hippocampal excitability through postsynaptic activation, and mGluR5 may do so through both pre- and post-synaptic mechanisms.     

Expression of the group I metabotropic glutamate receptor in the hippocampus of patients with mesial temporal lobe epilepsy

Immunocytochemical studies at light and electron microscopic levels in hippocampi of patients with mesial temporal lobe epilepsy showed mGluR1 and mGluR5 immunoreactivity in the molecular layer of the dentate gyrus and CA1 area, especially at the border between stratum oriens and alveus. By electron microscopy, degenerating neuronal elements were found in all areas studied. There were glial filamentous tangles which appeared similar to intranuclear inclusions in astrocytes in all areas studied. Reactive product for mGluR1 was localised only in post-synaptic elements. However, mGluR5 immunoreactivity was demonstrated in both post- and pre-synaptic elements in the molecular layer of the dentate gyrus and CA1 area. Reactive product for mGluR5 was also demonstrated in astrocytes and in the periphery of fibrillary tangles. We postulate that in patients with mesial temporal lobe epilepsy, mGluR1 may increase hippocampal excitability through postsynaptic activation, and mGluR5 may do so through both pre- and post-synaptic mechanisms.     

Acute intermittent nicotine treatment induces fibroblast growth factor-2 in the subventricular zone of the adult rat brain and enhances neuronal precursor cell proliferation

Over the past years, evidence has accumulated that stem cells are present in the adult brain, and generate neurons and/or glia from two active germinal zones: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. This study shows that acute intermittent nicotine treatment significantly enhances neuronal precursor cell proliferation in the SVZ of adult rat brain, but not in the SGZ of the hippocampus, and pre-treatment with mecamylamine, a nonselective nAChR antagonist, blocks the enhanced precursor proliferation by nicotine. This effect is supported by up-regulation of fibroblast growth factor-2 (FGF-2) mRNA in the SVZ and the expression of its receptor FGFR-1 in cells of SVZ showing precursor cells profile. It is also demonstrated that the nicotine effect on neuronal precursor proliferation is mediated by FGF-2 via fibroblast growth factor receptor 1 (FGFR-1) activation by showing that i.c.v. pre-treatment with anti-FGF-2 antibodies or with FGFR-1 inhibitor 3-[(3-(2-carboxyethyl)-4-methylpyrrol-2-yl)methylene]-2-indolinone (SU5402) blocks nicotine-induced precursor cell proliferation. This nicotine enhancement of neuronal precursor cell proliferation was not accompanied by an increase in the number of apoptotic cells. Taken together the present findings revealed the existence in the SVZ of the adult rat brain of a trophic mechanism mediated by FGF-2 and its receptor and regulated by nAchR activation. This possibility of in vivo regulation of neurogenesis in the adult brain by exogenous factors may aid to develop treatments stimulating neurogenesis with potential therapeutic implications.     

Characterization of adult neural stem cells and their relation to brain tumors

The adult mammalian brain contains neural stem cells that are capable of generating new neurons and glia over the course of a lifetime. Neural stem cells reside in 2 germinal niches, the subventricular zone (SVZ) and the dentate gyrus subgranular zone. These primary progenitors have been identified in their niche in vivo; these cells have characteristics of astrocytes. Recent studies have shown that adult SVZ stem cells are derived from radial glia, the stem cells in the developing brain, which in turn are derived from the neuroepithelum, the earliest brain progenitors. Thus, SVZ stem cells are a continuum from neuroepithelium to radial glia to astrocytes, and are contained within what has been considered the lineage for astrocytes. However, it seems that only a small subset of the astrocytes present in the adult brain have stem cell properties. Recent findings have shown that SVZ stem cell astrocytes express a receptor for platelet-derived growth factor (PDGF), suggesting that the ability to respond to specific growth factor stimuli, such as PDGF, epidermal growth factor and others, may be unique to these stem cell astrocytes. Intriguingly, activation of these same signaling pathways is widely implicated in brain tumor formation. Since the adult brain has very few proliferating cells capable of accumulating the numerous mutations required for transformation, the adult neural stem and/or progenitor cells may be likely candidates for the brain tumor cell of origin. Indeed, activation of the PDGF or epidermal growth factor pathways in adult neural stem or progenitor cells confers tumor-like properties on these cells, lending support to this hypothesis.     

Synaptic connections from multiple subfields contribute to granule cell hyperexcitability in hippocampal slice cultures

Limbic status epilepticus and preparation of hippocampal slice cultures both produce cell loss and denervation. This commonality led us to hypothesize that morphological and physiological alterations in hippocampal slice cultures may be similar to those observed in human limbic epilepsy and animal models. To test this hypothesis, we performed electrophysiological and morphological analyses in long-term (postnatal day 11; 40-60 days in vitro) organotypic hippocampal slice cultures. Electrophysiological analyses of dentate granule cell excitability revealed that granule cells in slice cultures were hyperexcitable compared with acute slices from normal rats. In physiological buffer, spontaneous electrographic granule cell seizures were seen in 22% of cultures; in the presence of a GABA(A) receptor antagonist, seizures were documented in 75% of cultures. Hilar stimulation evoked postsynaptic potentials (PSPs) and multiple population spikes in the granule cell layer, which were eliminated by glutamate receptor antagonists, demonstrating the requirement for excitatory synaptic transmission. By contrast, under identical recording conditions, acute hippocampal slices isolated from normal rats exhibited a lack of seizures, and hilar stimulation evoked an isolated population spike without PSPs. To examine the possibility that newly formed excitatory synaptic connections to the dentate gyrus contribute to granule cell hyperexcitability in slice cultures, anatomical labeling and electrophysiological recordings following knife cuts were performed. Anatomical labeling of individual dentate granule, CA3 and CA1 pyramidal cells with neurobiotin illustrated the presence of axonal projections that may provide reciprocal excitatory synaptic connections among these regions and contribute to granule cell hyperexcitability. Knife cuts severing connections between CA1 and the dentate gyrus/CA3c region reduced but did not abolish hilar-evoked excitatory PSPs, suggesting the presence of newly formed, functional synaptic connections to the granule cells from CA1 and CA3 as well as from neurons intrinsic to the dentate gyrus. Many of the electrophysiological and morphological abnormalities reported here for long-term hippocampal slice cultures bear striking similarities to both human and in vivo models, making this in vitro model a simple, powerful system to begin to elucidate the molecular and cellular mechanisms underlying synaptic rearrangements and epileptogenesis.     

Acupuncture improves cognitive deficits and regulates the brain cell proliferation of SAMP8 mice

Senescence-accelerated mouse prone 8 (SAMP8) is an autogenic senile strain characterized by early cognitive impairment and age-related deterioration of learning and memory. To investigate the effect of acupuncture on behavioral changes and brain cell events, male 4-month-old SAMP8 and age-matched homologous normal aging SAMR1 mice were divided into four groups: SAMP8 acupuncture group (Pa), SAMP8 non-acupoint control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). By Morris water maze test, the cognitive deficit of SAMP8 was revealed and significantly improved by "Yiqitiaoxue and Fubenpeiyuan" acupuncture. Meanwhile, by 5'-bromo-2'-deoxyuridine (BrdU) specific immunodetection, the decreased cell proliferation in dentate gyrus (DG) of SAMP8 was greatly enhanced by the therapeutic acupuncture, suggesting acupoint-related specificity. Even though no significant differences were found in ventricular/subventricular zones (VZ/SVZ) of the third ventricle (V3) and lateral ventricle (LV) between groups, we obtained interesting results: a stream-like distribution of newly proliferated cells presented along the dorsum of alveus hippocampi (Alv), extending from LV to corpus callosum (CC), and the therapeutic acupuncture showed a marked effect on this region. Our research suggests that acupuncture can induce different cell proliferation in different brain regions of SAMP8, which brings forth the need to explore further for the mechanism of cognitive deficits and acupuncture intervention in this field.     

移植的齿状回颗粒细胞在培养的大鼠海马组织上移行特征

为探讨齿状回颗粒细胞在培养的海马组织表面上的移行过程以及苔状纤维的投射特征,本实验从生后3d的绿色荧光蛋白(GFP)基因导入的SD大鼠海马组织切片中分离出齿状回颗粒细胞层,移植到培养的SD大鼠海马组织切片表面上,共同培养3～4d后,激光共聚焦显微镜观察。结果显示,97.6%的细胞移行到齿状回和CA3区,仅有2.4%细胞移行到CA2和CA1区。移行到齿状回颗粒细胞层的颗粒细胞投射苔状纤维到齿状回门区和CA3区的透明层,却不到CA2和CA1区。上述结果提示,在海马组织培养中移植的齿状回颗粒细胞的移行以及苔状纤维的投射方向明显受宿主的影响。     

High level of adenosine A1 receptor-like immunoreactivity in the CA2/CA3a region of the adult rat hippocampus.

We describe the immunocytochemical distribution of adenosine A1 receptors in the rat hippocampus. Adenosine A1 receptor-like immunoreactivity was seen on the cell soma and dendrites of pyramidal cells and the cell soma and proximal part of dendrites of granule cells, but not on glial cells. Developmentally, adenosine A1 receptor-like immunoreactivity was diffuse on postnatal day 7 and increased in intensity in individual cells by day 21. In the CA2/CA3a region, the adult pattern of A1 receptor distribution was established by day 28. In the adult rat hippocampus, rostrocaudal inspection revealed that immunoreactivity in CA2/CA3a was greatest. Confocal microscopy revealed differences in the staining patterns for the adenosine A receptor and synaptophysin, a marker of presynaptic terminals. This result suggests that the adenosine A1 receptor might have postsynaptic physiological functions. Double-labeling of adenosine A1 receptors and anterogradely-labeled fibers from the supramammillary nucleus showed that the fibers from the supramammillary nucleus terminate directly on the cell soma of the A1 receptor-immunopositive neurons in CA2/CA3a and the dentate gyrus. These results indicate that the adenosine A 1 receptor in CA2/CA3a and the dentate gyrus are in a position to regulate hippocampal theta activity and that resultant strong synaptic depression in CA2/CA3a could play a role in regulating the intrinsic signal flow between CA3 and CA1.     

雌激素对老年雌性小鼠齿状回和海马CA1区神经胶质细胞的影响——形态学观察和无偏性体视学定量分析

切除 2 0～ 2 4月龄 C5 7BL /6NIA小鼠双侧卵巢 ,随后于颈部皮下植入可持续释放 60 d的含 1.7mgβ-雌二醇 (E2 )或含等剂量胆固醇的安慰剂。用免疫组织化学结合无偏性体视学方法 ,分析小鼠齿状回和海马 CA1区小胶质细胞和星形胶质细胞形态和数量的变化。结果发现 :60 d E2处理老年雌性小鼠不仅可以抑制神经胶质细胞的激活 ,而且可以明显降低小胶质细胞和星形胶质细胞的总数 ;神经胶质细胞在脑内免疫和炎症反应过程中起着非常重要的作用。本实验的结果提示 ,雌激素可能通过调节胶质细胞介导的脑内炎症反应通路 ,发挥其神经保护作用。     

穹窿海马伞损伤对大鼠学习记忆和海马GFAP阳性神经胶质细胞的影响

为探讨穹隆海马伞损伤鼠学习记忆能力与海马胶质纤维酸性蛋白阳性细胞之间的关系 ,切断 SD成年大鼠左侧穹窿海马伞 ,用 Y迷宫和免疫组织化学结合图像分析系统测试大鼠学习记忆能力和海马胶质纤维酸性蛋白阳性细胞的变化状况及它们的相互关系。结果显示 :损伤 2周后 ,损伤组损伤侧海马 CA1 区辐射层和齿状回分子层胶质纤维酸性蛋白阳性细胞的数密度较正常组分别增多 3 0 .2 9%和 3 0 .15 % (都为 P<0 .0 1) ,胞体面积分别增加 16.0 4%和 19.42 % (都为 P<0 .0 1) ,齿状回分子层胶质纤维酸性蛋白阳性细胞体密度增大 19.40 % (P<0 .0 5 )。经相关分析 ,大鼠学习记忆能力与海马 CA1 区胶质纤维酸性蛋白阳性细胞数密度呈负相关 (r=-0 .83 6,P<0 .0 1) ,与齿状回数密度呈负相关 (r=-0 .792 ,P<0 .0 1)。提示海马星形胶质细胞可能参与学习记忆过程     

Leptomeningeal-derived doublecortin-expressing cells in poststroke brain

Increasing evidence indicates that neural stem/progenitor cells (NSPCs) reside in many regions of the central nervous system (CNS), including the subventricular zone (SVZ) of the lateral ventricle, subgranular zone of the hippocampal dentate gyrus, cortex, striatum, and spinal cord. Using a murine model of cortical infarction, we recently demonstrated that the leptomeninges (pia mater), which cover the entire cortex, also exhibit NSPC activity in response to ischemia. Pial-ischemia-induced NSPCs expressed NSPC markers such as nestin, formed neurosphere-like cell clusters with self-renewal activity, and differentiated into neurons, astrocytes, and oligodendrocytes, although they were not identical to previously reported NSPCs, such as SVZ astrocytes, ependymal cells, oligodendrocyte precursor cells, and reactive astrocytes. In this study, we showed that leptomeningeal cells in the poststroke brain express the immature neuronal marker doublecortin as well as nestin. We also showed that these cells can migrate into the poststroke cortex. Thus, the leptomeninges may participate in CNS repair in response to brain injury.     

Effects of transient cerebral ischemia on glial fibrillary acidic protein phosphorylation and immunocontent in rat hippocampus.

Transient global cerebral ischemia induced in rats by four-vessel occlusion for 20 min produced an increase in the immunocontent of glial fibrillary acidic protein and a protein phosphorylation response that was different in the CA1 and dentate gyrus areas of the hippocampus. We studied different times of reperfusion (one, four, seven, 14 and 30 days) and observed that the immunocontent and in vitro rate of phosphorylation of glial fibrillary acidic protein in the CA1 region was significantly increased at all intervals after the ischemic insult, indicating that the astrocytic response was maintained for at least 30 days. After reperfusion for 14 days a significant increase in the ratio "in vitro phosphorylation rate/immunocontent" in the CA1 region was observed when compared to control values, to other intervals and to the dentate gyrus, suggesting a hyperphosphorylation of this intermediate filament protein at this interval. In the dentate gyrus, an area less vulnerable to the insult, labelling and immunocontent of glial fibrillary acidic protein were equally increased from four days of reperfusion and the increase remained significant until 30 days, confirming that neuronal death is not the only determining factor for gliosis to occur. In control sham-operated animals, neither the CA1 region nor the dentate gyrus showed significant increases in labelling or immunocontent. Changes in the phosphorylation of glial fibrillary acidic protein may be essential for the plastic response of astrocytes to neuronal damage, as neurons and astrocytes can act as functional units involved in homeostasis, plasticity and neurotransmission.     

Heme oxgenase-1 is expressed in viable astrocytes and microglia but in degenerating pyramidal neurons in the kainate-lesioned rat hippocampus

The present study aimed to elucidate the distribution of heme oxygenase-1 (HO-1) in the hippocampus after intracerebroventricular injections of kainate. Very little or no staining of HO-1 was observed in the normal CA1, whilst moderate staining of dentate hilar neurons was observed in the dentate gyrus, in the normal hippocampus. At postinjection day 1, a slight increase in immunoreactivity in the neuropil of the lesioned CA fields and a marked increase in HO-1 immunoreactivity in glial cells of the stratum lacunosum moleculare of CA fields and the stratum moleculare of the dentate gyrus was observed. Electron microscopy showed that the glial cells had features of viable astrocytes. At postinjection day 3, glial cells in the dentate gyrus continued to express HO-1, whilst pyramidal neurons in the degenerating CA fields started to express intense HO-1 immunoreactivity in their cell bodies. At postinjection weeks 1–3, HO-1 was observed in glial cells in the center of the lesion, but also in neurons at the perifocal region of the glial scar. The glial cells were found to have features of viable astrocytes and microglia, whilst the neurons contained discontinuous cell membranes and nuclear outlines, and had features of degenerating neurons. Intense immunoreactivity was observed in the cytoplasm of the degenerating neurons. The density of staining was greater than that observed in astrocytes or microglia. Recent in vitro results on fibroblasts transfected with HO-1 cDNA showed that, despite cytoprotection with low (less than fivefold compared with untransfected cells) HO-1 activity, high levels of HO-1 expression (more than 15-fold) were associated with significant oxygen toxicity. These and the present observations suggest a destructive effect of increased expression of HO-1 in neurons, and possible novel therapeutic approaches involving overexpression of HO-1 must therefore be approached with caution. Electronic Publication     

Delayed cell migration in the developing rat brain following maternal omega 3 alpha linolenic acid dietary deficiency

Diminished levels of docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid (FA) synthesized from alpha linolenic acid (ALA, 18:3n-3), have been implicated in changes in neurotransmitter production, ion channel disruption and impairments of a variety of cognitive, behavioral and motor functions in the perinatal and adult mammal. Neuronal migration in the cortex and hippocampus of newborn and postnatal rats after ALA-deficiency, beginning on the 2nd day after conception and continuing for three weeks, was investigated. A marked decrease in the migration of bromodeoxyuridine⁽⁺⁾/neuronal nuclei⁽⁺⁾/neurofilament⁽⁺⁾ and glia fibrillary acidic protein^(–) neuronal cells to the dense cortical plate was accompanied by a corresponding abundance of non-migrating cells in several regions such as cortical layers IV–VI, corpus callosum and the sub-ventricular zone of ALA-deficient newborns. Similarly, a delayed migration of cells to CA1 and dentate gyrus areas was noticed while most cells were retained in the subicular area adjacent to the hippocampus. The reversibility of delay in migration in the hippocampus and cortex, after one and two weeks respectively, may be attributed to a temporary reelin disorganization or partial deficiency. Transient obstruction of neuronal cell migration may have long-lasting consequences on the organization of neuronal assemblies, on the connection between neurons (lateral connections) and acquisition of function in the adult brain.     

Physiological variability in brain-derived neurotrophic factor expression predicts dendritic spine density in the mouse dentate gyrus

Dendritic spines are the predominant sites of excitatory neurotransmission in the adult brain, and brain-derived neurotrophic factor (BDNF) is a well-characterized determinant of dendritic spine number and morphology. The relationship between BDNF expression and dendritic spine number is particularly evident in the hippocampus, where environmental conditions that enhance hippocampal BDNF levels also promote local increases in dendritic spine density. However, the relationship between physiological variability in hippocampal BDNF expression and spine number has yet to be assessed. To determine whether natural variability in BDNF expression is associated with hippocampal dendritic spine number, correlations between BDNF protein levels and dendritic spine density among Golgi-impregnated neurons in the hippocampal dentate gyrus and CA1 subfields were assessed in adult male C57Bl/6J mice. In the dentate gyrus, but not in the apical oblique dendrites of CA1 pyramidal cells, BDNF protein expression was significantly correlated with dendritic spine density. This observation suggests that there may be a subregionally specific relationship between hippocampal BDNF expression and the density of spines.     

成年大鼠去皮层血管引起前脑室下区祖细胞增殖迁移并形成迁移路至损伤部位(一)祖细胞增殖迁移的部位在背外侧脑室下区

成年哺乳动物脑室下区(SVZ)富有神经干细胞、神经细胞祖细胞和胶质细胞祖细胞,它们能生成新的神经细胞、星状胶质细胞和少突胶质细胞。SVZ中的神经细胞祖细胞能形成切线形式的嘴侧迁移流(RMS)到嗅球,在嗅球分化成成熟的中间神经元。近年来证明成年动物实验性脑损伤和变性疾病都能引起SVZ细胞增生并能向非嗅球区迁移。本研究将成年大鼠一侧大脑皮层血管去除,15d和30d后取前脑作冠状及矢状连续切片,用BrdU和PCNA抗体显示前脑室下区正在分裂的细胞;用Tuj1抗体显示神经元祖细胞;用GFAP和vimentin抗体显示胶质细胞祖细胞。结果证明去除一侧皮层血管引起术侧及其对侧的背外侧脑室下区(dl-SVZ)的上述免疫反应阳性细胞明显增多,并向胼胝体迁移,在胼胝体内形成放射形式迁移路至损伤部位。本研究表明背外侧脑室下区的范围应包括背外侧角、外侧伸展和侧脑室上壁的SVZ,它们是切线形式和放射形式两种不同方向的迁移路祖细胞的共同源地。