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1.
The brain extracellular matrix (ECM) has attracted growing interest due to its highly regulated spatiotemporal expression during development and maturation of central nervous system. The present study deals with the post‐natal appearance and transformation into adult distribution patterns of the ECM components related to proteoglycans (PGs) and glycoproteins (GPs) in the retrosplenial cortex (RSC) of albino rats at birth (P0), 1 week (P1), P2, P3, P4, P5, P6, P7 and P8. The differentiating PGs and GPs components of the ECM were shown to make their appearance as early as 1–2 weeks post‐natally. At this developmental stage, these components of the ECM appeared in association with some neurons and glia cells or diffusely localized at the neutrophill. Interestingly, Golgi complexes of labelled neurons were usually stained with lectin VVA or WFA, and this labelling dramatically disappeared on reaching P4. During P2–3, the pericoated neuronal cells underwent a progressive increment in number, and presented an inside‐out pattern of migration and differentiation (toward the V‐II cortical layers). On reaching P4, most of the coated neurons appeared distributed into the cortical layer IV and II. At a later stage (P5–8), the overall density and intensity of labelled neurons progressively increased and apparently reached the adult stage of development. They also displayed the usual differential labelling characteristics, after using the cationic iron colloid/lectin staining, for the first time at this juncture. The present findings indicated that the perineuronal ECM components are significantly correlated with age and suggest a possible developmental or biological significance including promotion of migration, as well as functional maturation of the retrosplenial neurons.  相似文献   

2.
The brain extracellular matrix (ECM) has attracted growing interest due to its highly regulated spatiotemporal expression during development and maturation of central nervous system. The present study deals with the post-natal appearance and transformation into adult distribution patterns of the ECM components related to proteoglycans (PGs) and glycoproteins (GPs) in the retrosplenial cortex (RSC) of albino rats at birth (P0), 1 week (P1), P2, P3, P4, P5, P6, P7 and P8. The differentiating PGs and GPs components of the ECM were shown to make their appearance as early as 1–2 weeks post-natally. At this developmental stage, these components of the ECM appeared in association with some neurons and glia cells or diffusely localized at the neutrophill. Interestingly, Golgi complexes of labelled neurons were usually stained with lectin VVA or WFA, and this labelling dramatically disappeared on reaching P4. During P2–3, the pericoated neuronal cells underwent a progressive increment in number, and presented an inside-out pattern of migration and differentiation (toward the V-II cortical layers). On reaching P4, most of the coated neurons appeared distributed into the cortical layer IV and II. At a later stage (P5–8), the overall density and intensity of labelled neurons progressively increased and apparently reached the adult stage of development. They also displayed the usual differential labelling characteristics, after using the cationic iron colloid/lectin staining, for the first time at this juncture. The present findings indicated that the perineuronal ECM components are significantly correlated with age and suggest a possible developmental or biological significance including promotion of migration, as well as functional maturation of the retrosplenial neurons.  相似文献   

3.
Hippocalcin participates in the maintenance of neuronal calcium homeostasis. In the present study, we examined the time-course changes of neuronal degeneration and hippocalcin protein level in the mouse hippocampus following pilocarpine-induced status epilepticus (SE). Marked neuronal degeneration was observed in the hippocampus after SE in a time-dependent manner, although neuronal degeneration differed according to the hippocampal subregions. Almost no hippocalcin immunoreactivity was detected in the pyramidal neurons of the cornu ammonis 1 (CA1) region from 6 h after SE. However, many pyramidal neurons in the CA2 region showed hippocalcin immunoreactivity until 24 h after SE. In the CA3 region, only a few hippocalcin immunoreactive cells were observed at 12 h after SE, and almost no hippocalcin immunoreactivity was observed in the pyramidal neurons from 24 h after SE. Hippocalcin immunoreactivity in the polymorphic cells of the dentate gyrus was markedly decreased from 6 h after SE. In addition, hippocalcin protein level in the hippocampus began to decrease from 6 h after SE, and was significantly decreased at 24 h and 48 h after pilocarpine-induced SE. These results indicate that marked reduction of hippocalcin level may be closely related to neuronal degeneration in the hippocampus following pilocarpine-induced SE.  相似文献   

4.
Earlier observations in neuroscience suggested that no new neurons form in the mature central nervous system. Evidence now indicates that new neurons do form in the adult mammalian brain. Two regions of the mature mammalian brain generate new neurons: (a) the border of the lateral ventricles of the brain (subventricular zone) and (b) the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. This review focuses only on new neuron formation in the dentate gyrus of the hippocampus. During normal prenatal and early postnatal development, neural stem cells (NSCs) give rise to differentiated neurons. NSCs persist in the dentate gyrus SGZ, undergoing cell division, with some daughter cells differentiating into functional neurons that participate in learning and memory and general cognition through integration into pre-existing neural networks. Axons, which emanate from neurons in the entorhinal cortex, synapse with dendrites of the granule cells (small neurons) of the dentate gyrus. Axons from granule cells synapse with pyramidal cells in the hippocampal CA3 region, which send axons to synapse with CA1 hippocampal pyramidal cells that send their axons out of the hippocampus proper. Adult neurogenesis includes proliferation, differentiation, migration, the death of some newly formed cells and final integration of surviving cells into neural networks. We summarise these processes in adult mammalian hippocampal neurogenesis and discuss the roles of major signalling molecules that influence neurogenesis, including neurotransmitters and some hormones. The recent controversy raised concerning whether or not adult neurogenesis occurs in humans also is discussed.  相似文献   

5.
Calbindin D-28k (CB), a calcium-binding protein, containing neurons in the hippocampus plays an important role in hippocampal excitability in epilepsy. In the present study, we investigated changes of CB immunoreactivity after adrenalectomy (ADX) in the hippocampus and dentate gyrus of the seizure sensitive gerbil, which is susceptible to seizure to identify roles of CB in epileptogenesis. The changes of the CB immunoreactivity after ADX were significant in the hippocampal CA1 region. By 24 h after ADX, CB-immunoreactive CA1 pyramidal cells and CB immunoreactivity increased. At this time, well-stained dendrites projected to the stratum radiatum. Thereafter, the CB immunoreactivity decreased time dependently by 96 h after ADX. In the dentate gyrus, the changes of CB-immunoreactive neurons were mainly observed in the granule cell layer. The number and immunoreactivity of CB-immunoreactive neurons was high at 24 h after ADX, thereafter, those decreased by 96 h after ADX. These results suggest that glucocorticoid has an important role in modulating the seizure activity and CB serves an inhibitory function, which regulates the seizure activity and output signals from the hippocampus.  相似文献   

6.
用SABC免疫组织化学技术,观察家兔海马各区nNOS阳性神经元在去卵巢及雌激素替代治疗后的形态结构及分布变化,为雌激素类药物防治绝经后老年性痴呆症提供理论依据。结果表明,家兔海马各区都有nNOS阳性神经元分布;去卵巢后海马nNOS阳性神经元的形态结构及分布变化有区域差异性:与假手术对照组相比,在海马CA1区、CA3区、齿状回(DG)阳性神经元数量明显减少(P0.05),而在CA2区数量明显增多(P0.05)。CA1、CA3区和DG的阳性神经元胞体截面积明显变小,最长突起长度明显变短,第一级突起数变少,与假手术组有显著差异(P0.05)。CA2区阳性神经元胞体截面积明显变小(P0.05),最长突起长度、第一级突起数增多,但差异不显著(P0.05);nNOS阳性神经元的4种指标在雌激素替代治疗组与假手术组之间无显著差异(P0.05)。结果提示:雌激素可能通过影响海马nNOS的表达来影响脑的学习和记忆功能。  相似文献   

7.
The mechanisms of ischemic neuronal death have been focused on glutamate receptor activation and subsequent elevation of intracellular Ca2+ concentration. The purpose of this study was to evaluate the effects of dizocilpine, an NMDA receptor antagonist, pretreatment on Fos expression and parvalbumin (PV, calcium binding protein) immunoreactivity in the hippocampus of the mongolian gerbil after global ischemic insults. The number of PV-immunoreactive (PV-ir) neurons in CA1 were significantly decreased from 1 day after cerebral ischemia, while dizocilpine pretreatment completely suppressed the loss of PV-ir neurons in CA1. Dizocilpine pretreatment also protected the structural loss of microtubule-associated protein 2 immunoreactivity in CA1 after ischemic insults. In addition, dizocilpine pretreatment increased Fos expression in both hippocampal CA3 and CA4 after 3 hr ischemic reperfusion as compared to that of the saline pretreated group. Subsequently, the Fos-defined cellular activity of PV-ir neurons was slightly increased by dizocilpine pretreatment in the hippocampal area. This study demonstrated that NMDA receptor mediated calcium influx was associated with the loss of PV-ir neurons in CA1 hippocampal region, and that dizocilpine pretreatment increased Fos expression and the neuronal activity of PV-ir neurons in the non-vulnerable region of hippocampus after cerebral ischemia. Based on this data, we conclude that the protective effect of dizocilpine may be induced by the regulation of calcium overload, or by the upregulation of a neuroregenerative initiator such as Fos protein.  相似文献   

8.
旨在研究限位栏饲养造成的制动应激对妊娠母猪神经元可塑性的影响，本研究选取6头8~9月龄配种成功的巴马小型母猪，随机分成两组，应激组（n=3）限位栏饲养，对照组（n=3）自由环境饲养，其余饲养管理一致。于妊娠第18天处死孕猪，取其海马和血液，使用ELISA、放射免疫法检测相关激素水平，制作海马石蜡切片进行尼氏染色和镀银染色后观察神经元丢失率、树突复杂度以及树突棘数量等，并采用Western blot检测海马脑源性神经营养因子（BDNF）表达水平。结果显示，应激组血浆中促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）、皮质醇（COR）水平均显著上升（P≤0.05），齿状回（DG）和CA3区出现神经元丢失现象，CA3区锥形细胞树突复杂度下降，神经元成熟树突棘和未成熟树突棘数量均显著降低，DG的成熟树突棘数量显著降低，且海马内的BDNF蛋白表达量较对照组降低70.6%（P≤0.01）。因此，制动应激减弱了孕猪大脑海马中CA3区和DG的神经元可塑性。  相似文献   

9.
采用股动脉放血并双侧颈总动脉夹闭制作全脑缺血再灌注模型 ,于术后 1d处死动物 ,取脑 ,制作石腊切片 ,通过 HE染色、Tunel检测 ,对海马 CA1 区锥体细胞形态进行了观察。结果表明 :在短暂性全脑缺血中 ,海马锥体细胞存在着凋亡和坏死 2种死亡形式 ;与对照组相比 ,缺血再灌注后 1d,海马 CA1 区损伤较重 ,出现了较多的凋亡细胞 ,而MT- 1可明显抑制锥体细胞的凋亡。本试验证明 :在脑缺血再灌注损伤中 ,细胞凋亡是神经元死亡的一种重要形式 ;MT- 1对脑缺血再灌注有明显神经保护作用  相似文献   

10.
Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy characterised by accumulation of resistant prion protein (PrPBSE), neuronal loss, spongiosus and glial cell proliferation. In this study, properties of the extracellular matrix (ECM) were investigated in boTg110 transgenic mice over-expressing the bovine cellular prion protein (PrPc) and infected with BSE. Using immunohistochemistry with Wisteria floribunda agglutinin as a specific marker for perineuronal nets (PNNs) and antibodies against aggrecan and hyaluronic acid binding protein, loss of ECM was correlated with PrPBSE accumulation and activation of astrocytes and microglia. PrPBSE accumulation and glial cell activation were detected from the earliest stages of the disease and increased in the terminal stages. Decreases in PNNs, aggrecan and hyaluronic acid were observed only in the terminal stages and correlated with the distribution of PrPBSE and activated glial cells. This study suggests that the loss of PNNs, aggrecan and hyaluronic acid is a consequence of PrPBSE accumulation. Degradation of ECM in BSE may be due to secretion of degradative enzymes by activated glial cells.  相似文献   

11.
对山羊胚胎大脑皮质形成及其神经元发育的形态学变化进行了研究，结果表明：（1）山羊胚胎不同类型大脑皮质的皮质板形成时间顺序为旧皮质、新皮质→海马皮质，与种系发生规律相反，提示神经系统内部结构的形成并非完全符合种系进化，而与动物个体组织结构自身的发展相关。不同类型大脑皮质皮质板的分化顺序为古皮质→旧皮质→新皮质，与种系发生的顺序相符。（2）山羊胚胎海马皮质锥体细胞的发育较早，按由深到浅的次序发育，而海马皮质中的非锥体细胞于第19周开始发育。梨状叶皮质锥体细胞发育的较早，最先出现在深层，颗粒层第18周出现。大脑新皮质各层神经元发育顺序依次为：内锥体层→外锥体层、多形层→内颗粒层→外颗粒层。各种类型皮质的神经元在出生前都未发育成熟。  相似文献   

12.
本研究旨在探讨右美托咪定干预氯胺酮致发育期大鼠神经损伤的影响及其可能的机制。7日龄SD大鼠随机分为对照组、氯胺酮组（氯胺酮20 mg·kg-1腹腔注射,每1.5 h注射1次,共5次）、右美托咪定组（右美托咪定腹腔注射15 μg·kg-1）和氯胺酮+右美托咪定组（氯胺酮注射前30 min,腹腔注射15 μg·kg-1右美托咪定）。最后1次给药90 min后,取大脑组织固定后进行尼氏染色;测定海马和皮质组织中CAT、GSH、MDA、IL-1β和IL-18的含量。尼氏染色结果显示,与对照组相比右美托咪定预先用药可以缓解氯胺酮导致的海马CA1区、CA3区和皮质区的神经元丢失。右美托咪定预处理还可以显著降低（P<0.05）海马和皮质MDA、IL-1β和IL-18水平,显著增加（P<0.05）CAT和GSH含量。综上表明,右美托咪定预处理能够有效降低海马和皮质MDA水平、增加CAT和GSH含量,并抑制炎症因子IL-1β和IL-18的分泌,在氯胺酮致发育期大鼠神经损伤时发挥神经保护作用。  相似文献   

13.
Previous studies have demonstrated that a loss of parvalbumin-immunoreactive (PV-ir) neurones is observed in the hippocampus after transient cerebral ischaemia. However, whether the loss of parvalbumin (PV) immunoreactivity is related to the over-production of nitric oxide (NO) during cerebral ischaemia has not been evaluated. This study was designed to test the effect of 7-nitroindazole pre-treatment (7-NI, 50 mg/kg), a selective neuronal NO synthase inhibitor, on PV immunoreactivity and its cellular activity following forebrain ischaemia. PV-ir neurones in the hippocampus of the control group were widely distributed in the pyramidal cell layer and stratum oriens of CA1 and CA3, and the granular cell layer of dentate gyrus. 7-NI pre-treatment completely suppressed the reduction of PV immunoreactivity in CA1 that was observed in the ischaemia-induced group. Subsequently, 7-NI pre-treatment also protected against the structural loss of microtubule-associated protein 2 (MAP2) immunoreactivity in CA1 after ischaemic insult. In addition, the Fos-defined neuronal activity of PV-ir neurones was slightly increased by the 7-NI pre-treatment 3 h after ischaemia. Based on these data, we conclude that the neuronal toxicity of NO may be involved in the loss of PV-ir neurones after cerebral ischaemia.  相似文献   

14.
Microglia are evenly distributed throughout the brain parenchyma. They respond rapidly to a variety of alterations in the microenvironment of the brain and act as sensors for pathological events in the brain. In the present study, we investigated the age-dependent changes in the immunoreactivity and protein level of ionized calcium-binding adapter molecule 1 (Iba-1), a microglial marker, in the CA1 region of the gerbil hippocampus. Iba-1 immunoreactive microglia were detected in the hippocampal CA1 region of the postnatal month 1 (PM 1) group. Iba-1 positive microglia were morphologically inactive between the PM 1 and PM 12 stages. Some Iba-1 immunoreactive microglia were present in the active form in the hippocampal CA1 region of the PM 18 and PM 24 groups. The Iba-1 protein levels in hippocampal CA1 homogenates were decreased in the PM 1 through PM 6 groups and increased in an age-dependent manner thereafter. These results suggest that Iba-1 immunoreactive microglia in the active form were detected in the hippocampal CA1 region in the PM 18 and PM 24 groups. This result may be associated with an age-dependent susceptibility to neurodegenerative diseases associated with the hippocampus.  相似文献   

15.
Over 100 free-ranging adult California sea lions (Zalophus californianus) and one Northern fur seal (Callorhinus ursinus), predominantly adult females, were intoxicated by domoic acid (DA) during three harmful algal blooms between 1998 and 2000 in central and northern California coastal waters. The vector prey item was Northern anchovy (Engraulis mordax) and the primary DA-producing algal diatom was Psuedonitzschia australis. Postmortem examination revealed gross and histologic findings that were distinctive and aided in diagnosis. A total of 109 sea lions were examined, dying between 1 day and 10 months after admission to a marine mammal rehabilitation center. Persistent seizures with obtundation were the main clinical findings. Frequent gross findings in animals dying acutely consisted of piriform lobe malacia, myocardial pallor, bronchopneumonia, and complications related to pregnancy. Gross findings in animals dying months after intoxication included bilateral hippocampal atrophy. Histologic observations implicated limbic system seizure injury consistent with excitotoxin exposure. Peracutely, there was microvesicular hydropic degeneration within the neuropil of the hippocampus, amygdala, pyriform lobe, and other limbic structures. Acutely, there was ischemic neuronal necrosis, particularly apparent in the granular cells of the dentate gyrus and the pyramidal cells within the hippocampus cornu ammonis (CA) sectors CA4, CA3, and CA1. Dentate granular cell necrosis has not been reported in human or experimental animal DA toxicity and may be unique to sea lions. Chronically, there was gliosis, mild nonsuppurative inflammation, and loss of laminar organization in affected areas.  相似文献   

16.
研究了癫痫对幼龄大鼠中枢神经元的损伤以及应用依托咪酯后的影响,旨在探讨依托咪酯对癫痫大鼠神经元的保护作用。大鼠随机分为试验组（72只）和对照组（C组,6只）,试验组分为模型组（KA组）、依托咪酯治疗组（Et组）,采用海仁酸（KA）诱导幼龄大鼠癫痫模型,通过甲酚紫染色观察受损的神经细胞以及热休克蛋白HSP-70的免疫反应阳性结果作为神经元损伤程度的指标,通过电镜观察海马神经元。结果显示,在KA组海马的CA3和DG区两种反应的阳性细胞数明显增多,而注射依托咪酯的大鼠海马相应区域阳性细胞数目明显减少。电镜观察结果显示依托咪酯组海马神经元损伤被抑制。结果表明,依托咪酯具有对海仁酸癫痫模型神经毒性的抑制作用,对海马神经元起到一定的保护作用。  相似文献   

17.
The hippocampus is affected by various stimuli that include hyperglycemia, depression, and ischemia. Calcium-binding proteins (CaBPs) have protective roles in the response to such stimuli. However, little is known about the expression of CaBPs under diabetic conditions. This study was conducted to examine alterations in the physiological parameters with type 1 diabetes induced with streptozotocin (STZ) as well as time-dependent changes in the expression of two CaBPs changes of were being evaluated. Rats treated with STZ (70 mg/kg) had high blood glucose levels (>21.4 mmol/L) along with increased food intake and water consumption volumes compared to the sham controls. In contrast, body weight of the animals treated with STZ was significantly reduced compared to the sham group. CB-specific immunoreactivity was generally increased in the hippocampal CA1 region and granule cell layer of the dentate gyrus (DG) 2 weeks after STZ treatment, but decreased thereafter in these regions. In contrast, the number of PV-immunoreactive neurons and fibers was unchanged in the hippocampus and DG 2 weeks after STZ treatment. However, this number subsequently decreased over time. These results suggest that CB and PV expression is lowest 3 weeks after STZ administration, and these deficits lead to disturbances in calcium homeostasis.  相似文献   

18.
Astrocytes perform neuron-supportive tasks, repair and scarring process in the central nervous system. In this study, we observed glial fibrillary acidic protein (GFAP), a marker for astrocytes, immunoreactivity in the dentate gyrus and hippocampus proper (CA1-3 region) of adult (2-3 years of age) and aged (10-12 years of age) dogs. In the adult group, GFAP immunoreactive astrocytes were distributed in all layers of the dentate gyrus and CA1-3 region, except in the stratum pyramidale of the CA1-3 region. In the aged group, GFAP immunoreactivity decreased markedly in the molecular layer of the dentate gyrus. However, GFAP immunoreactivity in the CA1-3 region increased in all layers, and the cytoplasm of GFAP immunoreactive astrocytes was hypertrophied. GFAP protein levels in the aged dentate gyrus decreased; however, GFAP levels in the CA1-3 region increased. These results suggest that the morphology of astrocytes and GFAP protein levels in the hippocampal dentate gyrus and CA1 region are changed, respectively, with age.  相似文献   

19.
大鼠短暂性全脑缺血再灌注后海马神经元动态变化   总被引：2，自引：0，他引：2  
采用股动脉放血并双侧颈总动脉夹闭制作大鼠全脑缺血再灌注模型,分别于术后6h、1d、3d、5d处死动物,取脑,制作石蜡切片和冰冻切片,通过HE染色、TUNEL检测及Caspase-3活性测定,对大鼠海马各区锥体细胞形态进行动态观察。结果表明:在短暂性全脑缺血中,海马锥体细胞存在着凋亡和坏死两种死亡形式,细胞凋亡在海马各区中的分布是一动态过程,各区对缺血易损伤性的顺序是:CA1及门区>CA2>CA3>齿状回;脑缺血再灌注不同时间,海马锥体细胞中DNA断裂及Caspase-3的表达与细胞凋亡呈现相似的变化趋势,且DNA的断裂早于Caspase-3的表达;与青年组相比,老年组海马神经元出现凋亡时间早且损伤严重。试验证明:在脑缺血再灌注损伤中,海马各区存在着缺血耐受性差异;细胞凋亡是神经元死亡的一种重要形式。  相似文献   

20.
OBJECTIVE: To quantify and compare biochemical characteristics of the extracellular matrix (ECM) of specimens harvested from tensional and compressive regions of the superficial digital flexor tendon (SDFT) of horses in age classes that include neonates to mature horses. SAMPLE POPULATION: Tendon specimens were collected on postmortem examination from 40 juvenile horses (0, 5, 12, and 36 months old) without macroscopically visible signs of tendonitis. PROCEDURE: Central core specimens of the SDFT were obtained with a 4-mm-diameter biopsy punch from 2 loaded sites, the central part of the mid-metacarpal region and the central part of the mid-sesamoid region. Biochemical characteristics of the collagenous ECM content (ie, collagen, hydroxylysylpyridinoline crosslink, and pentosidine crosslink concentrations and percentage of degraded collagen) and noncollagenous ECM content (percentage of water and glycosaminoglycans, DNA, and hyaluronic acid concentrations) were measured. RESULTS: The biochemical composition of equine SDFT was not homogeneous at birth with respect to DNA, glycosaminoglycans, and pentosidine concentrations. For most biochemical variables, the amounts present at birth were dissimilar to those found in mature horses. Fast and substantial changes in all components of the matrix occurred in the period of growth and development after birth. CONCLUSIONS AND CLINICAL RELEVANCE: Unlike cartilage, tendon tissue is not biochemically blank (ie, homogeneous) at birth. However, a process of functional adaptation occurs during maturation that changes the composition of equine SDFT from birth to maturity. Understanding of the maturation process of the juvenile equine SDFT may be useful in developing exercise programs that minimize tendon injuries later in life that result from overuse.  相似文献   

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