Effect of Batroxobin on Expression of Neural Cell Adhesion Molecule in Temporal Infarction Rats and Spatial Learning and Memory Disorder

The effect of Batroxobin expression of neural cell adhesion molecule (NCAM) in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemical methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats and at the same time NCAM expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of NCAM immune reactive cells of Batroxobin-treated rats was more than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats and the regulation of the expression of NCAM is probably related to the neuroprotective mechanism.

Effects of Batroxobin on Spatial Learning and Memory Disorder of Rats with Temporal Ischemia and the Expression of HSP32 and HSP70

The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri`s water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats in searching a goal were significantly longer than those of the sham-operated rats and at the same time HSP32 and HSP70 expression of left temporal ischemic region in rats was significantly increased as compared with the sham-operated rats. However, the mean reaction time and distance of the Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of HSP32 and HSP70 immune reactive cells of Batroxobin-treated rats was also less than that of the ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats; and the down-regulation of the expression of HSP32 and HSP70 is probably related to the attenuation of ischemic injury.

Effects of Yizhi Capsule (益智胶囊) on Learning and Memory Disorder and β-amyloid Peptide Induced Neurotoxicity in Rats

To explore the effects of Yizhi Capsule （益智胶囊, YZC） on learning and memory disorder and β-amyloid peptide induced neurotoxicity in rats. Methods： Various doses of YZC were administered to Sprague-Dawley （SD） rats for 8 consecutive days, twice a day. On the 8th day of the experiment, scopolamine hydrobromide was intraperitoneally injected to every rat and Morris water maze test and shuttle dark avoidance test were carried out respectively to explore the changes of learning and memory capacities in the rats. Resides, after the cerebral cortical neurons of newborn SD rats aged within 3 days were cultured in vitro for 7 days, drug serum containing YZC was added to the cultured neurons before or after β amyloid peptide25-35 （Aβ25-35） intoxication to observe the protective effect of YZC on neurotoxicity by MTT assay and to determine the LDH content in the supernatant. Results： Compared with those untreated with YZC, the rats having received YZC treatment got superiority in shorter time of platform seeking in Morris water maze test, as well as elongated latent period and less times of error in shuttle dark avoidance test. On the cultured neurons, YZC drug serum could effectively increase the survival rate of Aβ25-35 intoxicated neurons and reduce the LDH contents in cultured supernatant. Conclusion： YZC has an action of improving learning and memory disorder, and good protective effect on Aβ25-35 induced neurotoxicity in SD rats. KEY WORDS

Microglia regulation of synaptic plasticity and learning and memory

Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity.Through the C1 q,C3 and CR3"Eat Me"and CD47 and SIRPα"Don't Eat Me"complement pathways,as well as other pathways such as CX3 CR1 signaling,resting microglia regulate synaptic pruning,a process crucial for the promotion of synapse formation and the regulation of neuronal activity and synaptic plasticity.By mediating synaptic pruning,resting microglia play an important role in the regulation of experience-dependent plasticity in the barrel cortex and visual cortex after whisker removal or monocular deprivation,and also in the regulation of learning and memory,including the modulation of memory strength,forgetfulness,and memory quality.As a response to brain injury,infection or neuroinflammation,microglia become activated and increase in number.Activated microglia change to an amoeboid shape,migrate to sites of inflammation and secrete proteins such as cytokines,chemokines and reactive oxygen species.These molecules released by microglia can lead to synaptic plasticity and learning and memory deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and other neurological or mental disorders such as autism,depression and post-traumatic stress disorder.With a focus mainly on recently published literature,here we reviewed the studies investigating the role of resting microglia in synaptic plasticity and learning and memory,as well as how activated microglia modulate disease-related plasticity and learning and memory deficits.By summarizing the function of microglia in these processes,we aim to provide an overview of microglia regulation of synaptic plasticity and learning and memory,and to discuss the possibility of microglia manipulation as a therapeutic to ameliorate cognitive deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and mental disorders.

从“脾主升清”探讨瓦伯格效应在学习记忆障碍中的作用

学习记忆障碍病位主要在脑,与脾、心、肾、肝功能失调密切相关,尤其是脾,其居中土,主管气机升降,斡旋一身之气血以濡养脑窍。本文通过论述“脾主升清”的生理功能,探讨其在学习记忆障碍中的作用。瓦伯格效应以快速高效的方式产生能量以维持大脑正常功能,与中医脾主升清的功能在一定程度上相契合。因此,以“脾主升清”立论,探讨学习记忆障碍的病理基础,并从中西医方面阐述瓦伯格效应紊乱是本病的重要特征,有助于深入探讨助脾升清法治疗学习记忆障碍的作用,为该病中医治疗提供新思路。

Efficacy of electroacupuncture stimulating Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)on spatial learning and memory deficits in rats with insomnia induced by para-chlorophenylalanine:a single acupoint vs combined acupoints

OBJECTIVE:To investiage the effect of electroacupuncture(EA)at a single acupoint of Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6)and at combined acupoints of Shenmen(HT7)and Baihui(GV20)and Sanyinjiao(SP6)on the PKA/CREB and BDNF/TrkB signaling,as well as neuroapoptosis and neurogenesis in hippocampus and elucidate the underlying mechanism of single and combined acupoints on ameliorating spatial learning and memory deficits in a rat model of primary insomnia.METHODS:Primary insomnia was modeled by intraperitoneal injection of para-chlorophenylalanine(PCPA)once daily for 2 d.EA was applied at Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),or Shenmen(HT7)+Baihui(GV20)+Sanyinjiao(SP6)(combined)for 30 min daily for 4 d.Spatial learning and memory function was evaluated by the Morris water maze(MWM)test.Protein expressions of hippocampal cAMP-dependent protein kinase(PKA)-Cβ,phosphorylated cAMP-responsive element-binding protein(p-CREB),brainderived neurotrophic factor(BDNF),and tyrosine kinase receptor B(TrkB)were evaluated by Western blotting.Neuronal apoptosis in the hippocampus was detected with the transferase-mediated dUTP-X nick end labeling assay.Endogenous neurogenesis was examined with bromodeoxyuridine staining.The MWM test and hippocampal p-CREB,BDNF,and TrkB protein levels in the combined acupoints group were evaluated after the administration of a PKA-selective inhibitor(H89).RESULTS:Spatial learning and memory were significantly impaired in rats with insomnia.The spatial learning deficits were ameliorated in the Shenmen(HT7),Baihui(GV20),Sanyinjiao(SP6),and combined groups;this improvement was significantly greater in the combined group than the single acupoint groups.The spatial memory impairment was improved in the combined,Baihui(GV20),and Shenmen(HT7)groups,but not the Sanyinjiao(SP6)group.The expressions of PKA-Cβ,p-CREB,BDNF,and TrkB were decreased in rats with insomnia.All these proteins were significantly upregulated in the combined group.PKA/p-CREB protein levels were elevated in the Baihui(GV20)and Shenmen(HT7)groups,whereas BDNF/TrkB expression was upregulated in the Sanyinjiao(SP6)group.The staining results showed significant attenuation of hippocampal cell apoptosis and increased numbers of proliferating cells in the combined group,whereas the single acupoint groups only showed decreased numbers of apoptotic cells.In the combined group,the PKA inhibitor reversed the improvement of spatial memory and upregulation of pCREB expression caused by EA,but did not affect its activation of BDNF/TrkB signaling.CONCLUSIONS:EA at the single acupoints Baihui(GV20),Shenmen(HT7),or Sanyinjiao(SP6)had an ameliorating effect on the spatial learning and memory deficits induced by insomnia.EA at combined acupoints exerted a synergistic effect on the improvements in spatial learning and memory impairment in rats with insomnia by upregulating the hippocampal PKA/CREB and BDNF/TrkB signaling,facilitating neurogenesis,and inhibiting neuronal apoptosis.These findings indicate that EA at combined acupoints[(Baihui(GV20),Shenmen(HT7),and Sanyinjiao(SP6)]achieves a more pronounced regulation of hippocampal neuroplasticity than EA at single acupoints,which may partly explain the underlying mechanisms by which EA at combined acupoints exerts a better ameliorative effect on the cognitive dysfunction caused by insomnia.

Protective Effects and Mechanism of Puerarin on Learning-Memory Disorder after Global Cerebral Ischemia-Reperfusion Injury in Rats

Objective:To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats,and to explore its mechanism of action.Methods:The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats.Rats were intraperitoneally injected with puerarin(100 mg/kg) 1 h before ischemia and once every 6 h afterwards.The learning-memory ability was evaluated by the passive avoidance test.Th...

N-甲基-D-天冬氨酸受体阻断剂缓解HIV-1/gp120诱导大鼠学习记忆障碍的作用及机制

目的研究阻断N-甲基-D-天冬氨酸受体(N-methyl-D-aspartic acid receptor,NMDAR)对gp120诱导大鼠学习记忆障碍的缓解作用及机制。方法(1)32只SD大鼠随机分为空白对照组、假手术组、gp120组、gp120+Memantine组。除空白对照组外,其余组均双侧海马注射,建立大鼠学习记忆障碍模型。Memantine于造模前3天腹腔注射给药。注射后第3~8天进行水迷宫实验,第10天分离各组大鼠海马,qRT-PCR检测TNF-α、IL-10、CXCL-12表达。(2)以gp120和NMDA诱导建立细胞损伤模型;将细胞分为空白对照组、gp120组、gp120+Memantine组、NMDA组、NMDA+Memantine组。Memantine需预先处理40 min。MTT、LDH法检测细胞存活率和LDH含量,ELISA法检测细胞IL-1β、TNF-α含量,AO/EB染色检测细胞凋亡,qRT-PCR检测IRE1α、JNK、GRP78和CHOP表达。结果(1)与gp120组相比,gp120+Memantine组逃避潜伏期及游泳距离明显减少,目标象限时间百分比和平台穿越次数增加,TNF-α、CXCL-12的mRNA表达量减少。(2)与gp120组和NMDA组相比,gp120+Memantine组和NMDA+Memantine组细胞活力上升,细胞状态良好,IL-1β、TNF-α、IRE1α、JNK、GRP78和CHOP的表达量下降。结论NMDAR参与了gp120诱导的HAND,阻断NMDAR可以显著改善gp120诱导的大鼠学习记忆障碍和神经细胞损伤,其机制与抑制神经炎症、凋亡反应和内质网应激相关IRE1α-JNK-CHOP通路有关。

长春西汀对抑郁大鼠MECT后学习记忆障碍的改善作用机制

目的探究长春西汀对抑郁大鼠无抽搐电休克(MECT)后学习记忆障碍的改善作用机制。方法采用慢性温和不可预见性应激(CUMS)法构建抑郁症大鼠模型,将30只抑郁症大鼠随机分为抑郁组、MECT组、MECT+长春西汀(10 mg/kg)组,每组10只,另选取10只未处理的健康大鼠作对照组。采用Morris水迷宫实验和新物体识别实验检测学习记忆能力,糖度偏好实验评估抑郁状态,制备海马脑片进行电生理实验,高尔基染色检测树突棘密度,qPCR和Western blotting实验检测内源性大麻素相关基因[二酰基甘油脂肪酶(DAGLα)、单酰甘油脂肪酶(MAGL)和内源性大麻素Ⅰ型受体(CB1R)]表达。此外注射慢病毒下调海马中CB1R和DAGLα表达,再次建模与处理后,进行行为学检测。结果与对照组比较,抑郁组糖度偏好、空间探索时间、相对辨别指数、长时程增强(LTP)、树突棘密度、DAGLα和CB1R表达降低,逃避潜伏期和MAGL表达升高(P<0.05);与抑郁组比较,MECT组糖度偏好、逃避潜伏期和MAGL表达升高,空间探索时间、相对辨别指数、LTP、树突棘密度、DAGLα和CB1R表达降低(P<0.05),MECT+长春西汀组糖度偏好、空间探索时间、相对辨别指数、LTP、树突棘密度、DAGLα和CB1R表达升高,逃避潜伏期和MAGL表达降低(P<0.05);与MECT组比较,MECT+长春西汀组糖度偏好、空间探索时间、相对辨别指数、LTP、树突棘密度、DAGLα和CB1R表达升高,逃避潜伏期和MAGL表达降低(P<0.05);慢病毒下调DAGLα或CB1R表达后,可抑制长春西汀对抑郁大鼠MECT治疗后行为学表现的改善作用。结论长春西汀可明显改善抑郁大鼠MECT治疗后的学习记忆障碍,可能与调节内源性大麻素相关基因表达、增强突触可塑性有关。

睡眠障碍对儿童学习记忆的影响及其机制研究进展

睡眠障碍是目前常见的一种可以引起心血管系统、神经系统疾病等的病理、生理过程。大量数据显示睡眠障碍问题越来越趋于年轻化,但目前对于儿童睡眠障碍问题的研究与成人相比较少。睡眠障碍会对儿童生长发育、学习记忆、免疫功能等产生不利影响,甚至可能增加远期抑郁症发生的风险。鉴于目前睡眠障碍问题越来越严重,且对学习记忆等认知功能的影响日益突出,全面了解常见的儿童睡眠障碍产生的原因和睡眠障碍对学习记忆的影响及其作用机制具有重要的临床意义,可为临床上儿童睡眠障碍治疗方式的选择提供新思路。

Role of Eclipta prostrata extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats

OBJECTIVE: To investigate the role of Eclipta prostrata (E. prostrata) extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats. METHODS: Rats were divided into five groups, with 10 animals in each group. Aging rats were produced by treatment with 100 mg·kg-1·d-1 of D-galactose for 6 weeks. Rats in the E. prostrata treatment groups received an aqueous extract of E. prostrata orally at a concentration of 50, 100, or 200 mg·kg-1· d-1 for 3 weeks. Animals in both the normal and model groups were treated with similar volumes of saline. Spatial memory performance was measured using the Morris water maze. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were analyzed using real- time quantitative PCR and spectrophotometry,respectively. The levels of induced nitric oxide synthase (iNOS), nitric oxide (NO), dopamine (DA), norepinephrine (NE), and serotonin (5-HT) were determined using enzyme-linked immunosorbent assay and spectrophotometry. RESULTS: Compared with the normal group, rats in the D-galactose-treated model group exhibited significant memory loss. There was severe damage to the hippocampal CA1 area, and expression levels of SOD, CAT, GPx, and GR were significantly decreased in the model group compared with the normal group. In the model group, levels of iNOS and NO were significantly increased compared with the normal group. However, treatment with E. prostrata extract reversed the conditions caused by D-galactose- induced aging, especially in the groups with higher treatment concentrations. Compared with the normal group, the levels of DA, NE, and 5-HT were significantly lower in the D-galactose-treated model group. In the E. prostrata extract-treated groups, however, there was a dose-dependent upregulation of DA, NE, and 5-HT expression. CONCLUSION: Our results suggest that administration of E. prostrata extract can result in an improvement in the learning and memory impairments that are induced by D-galactose treatment in rats. This improvement may be the result of enhanced antioxidative ability, decreased iNOS and NO levels, and the induction of DA, NE, and 5-HT expression in the brain.

基于fNIRS的游戏成瘾识别方法研究

网络游戏成瘾已在世界范围内发展成为一种新型精神疾病。随着脑功能成像技术的不断发展,功能性近红外光谱技术(functional Near-Infrared Spectroscopy,fNIRS)已经被广泛应用于各个领域中。本文根据网络游戏成瘾量表筛选出22名受试者,利用fNIRS采集受试者在停止信号任务期间前额叶脑血氧饱和度数据。使用3种传统机器学习方法和长短期记忆(Long Short-Term Memory,LSTM)神经网络对fNIRS信号进行分类,来区分游戏成瘾患者和健康人,得到的最高准确率为85.7%。本文利用fNIRS在游戏成瘾识别方面做了有益的尝试。

Effects of subconvulsive electrical stimulation to the hippocampus on emotionality and spatial learning and memory in rats

Objective To observe the effects of repeated subconvulsive electrical stimuli to the hippocampus on the emotional behavior and spatial learning and memory ability in rats.Methods One hundred and eight male Wistar rats were randomized into 3 groups. Animals in group SE (n = 42) were given subconvulsive electrical stimulation to the hippocampus through a constant pulsating current of 100 μA with an intratrain frequency of 25 Hz, pulse duration of 1 millisecond, train duration of 10 seconds and interstimulus interval of 7 minutes, 8 times a day, for 5 days. In the electrode control group or CE group (n = 33), animals were implanted with an electrode in the hippocampus, but were not stimulated. Group NC (n =33) animals received no electrode or any stimulation. The emotional behavior of experimental rats was examined by activity in an unfamiliar open field and resistance to capture from the open field, while the spatial learning and memory ability was measured during training in a Morris water maze.Results The stimulated rats tested 1 month after the last round of stimulation displayed substantial decreases in open field activity (scale: 10. 4±2. 3, P<0. 05) and increases in resistance to capture (scale: 2. 85±0. 56, P < 0. 01 ). The amount of time for rats in group SE to find the platform (latency) as a measurement for spatial bias was prolonged (29±7) seconds after 15 trials in the water maze, P<0. 05). The experimental rats swam aimlessly in all four pool quadrants during the probe trial in the Morris water maze.Conclusions Following repeated subconvulsive electrical stimuli to the hippocampus, rats displayed long-lasting significant abnormalities in emotional behavior, increased anxiety and defensiveness, enhanced ease to and delayed habituation to startlement, transitory spatial learning and memory disorder, which parallels many of the symptoms in posttraumatic stress disorder patients.

癫痫清颗粒介导线粒体自噬对P301S小鼠tau蛋白的影响

目的研究癫痫清颗粒介导线粒体自噬对P301S小鼠tau蛋白的影响。方法将36只P301S小鼠按体重分为模型组、癫痫清颗粒组(12.48 g/kg)和盐酸多奈哌齐组(阳性对照,1.3 mg/kg),每组12只;另取C57BL6小鼠10只,作为对照组。各药物组小鼠灌胃相应药液,对照组和模型组灌胃等体积水;灌胃体积均为20 mL/kg,每天1次,连续5个月。实验期间,观察各组小鼠的一般状况;末次给药后,借助Y迷宫和Morris水迷宫实验检测小鼠的学习记忆能力;以苏木精-伊红染色法观察其脑组织形态学改变,以尼氏染色法观察其脑组织神经细胞结构和尼氏体数量;以免疫组织化学法检测其脑组织中丝氨酸202/苏氨酸205位点磷酸化tau(简称“AT8”)蛋白的表达水平,Western blot法检测脑组织中线粒体自噬相关蛋白[PTEN诱导激酶1(PINK1)、Parkin、微管相关蛋白1轻链3B(LC3B)、p62]、突触相关蛋白[突触后密度蛋白95(PSD-95)、突触生长蛋白(SYP)、生长相关蛋白43(GAP-43)]的表达水平和tau蛋白的磷酸化水平[以丝氨酸199(Ser199)、Ser202的磷酸化水平表示]。结果模型组小鼠出现毛发变白、体重下降、下肢瘫痪等症状;其脑组织海马结构欠完整,神经细胞膜及细胞结构亦不完整;其自发交替反应率、穿越平台次数、细胞质内尼氏体数量和PINK1、Parkin、LC3B、SYP、GAP-43、PSD-95蛋白的表达水平均较对照组显著降低,游泳潜伏期(第4、5天)、AT8和p62蛋白的表达水平、Ser199和Ser202蛋白的磷酸化水平均较对照组显著升高或延长(P<0.05或P<0.01)。与模型组比较,各药物组小鼠上述症状和指标均得以显著改善(P<0.05或P<0.01)。结论癫痫清颗粒可有效改善P301S小鼠的认知功能障碍,作用可能与介导线粒体自噬,减少tau蛋白过度磷酸化,上调脑组织中突触相关蛋白的表达,修复受损神经细胞有关。

吡格列酮对淀粉样β蛋白片段1-42引起的大鼠学习记忆障碍及海马炎症反应的影响

目的观察吡格列酮(Pio)是否对学习记忆障碍有治疗改善作用。方法大鼠随机分为正常对照组,淀粉样β蛋白片段1-42(Aβ1-42)损伤组,Aβ1-42+Pio20,40及80mg·kg-1组。于d1和2,Pio处理组大鼠灌胃给予Pio,正常对照组和Aβ1-42损伤组灌胃给予0.2%二甲亚砜。d2给药处理后,Aβ1-42损伤组及Pio处理组大鼠左侧脑室内单次注射Aβ1-425μL(2.0mmol·L-1)制备大鼠痴呆动物模型,正常对照组注射等量生理盐水。同时,d2开始进行Morris水迷宫实验,连续6d;水迷宫实验结束后,Nissl染色观察海马CA1区锥体神经元改变和免疫组织化学法观察星形胶质细胞改变;Western蛋白印迹法检测白细胞介素(IL)-1β和诱导型一氧化氮合酶(iNOS)的表达水平。结果脑室注射Aβ1-42可引起大鼠学习记忆能力明显降低,表现为逃避潜伏期延长,原平台象限游泳时间占总时间的比例降低;形态学上表现为海马CA1区锥体神经元的损伤和星形胶质细胞的激活和浸润;同时海马IL-1β和iNOS蛋白表达也显著增加。Pio(40和80mg·kg-1)能明显改善大鼠学习记忆能力,减轻海马CA1区锥体神经元损伤和星形胶质细胞激活与浸润,抑制Aβ1-42引起的IL-1β及iNOS蛋白表达增加。结论Pio能改善Aβ1-42损伤大鼠学习记忆障碍,抑制海马炎症反应可能是其机制之一。

电针对穹隆——海马伞损伤老年痴呆大鼠学习记忆行为影响的实验研究

目的探讨电针改善老年痴呆大鼠学习记忆行为的效果。方法采用损伤穹隆—海马伞的方法造成胆碱能系统损害学习记忆障碍痴呆模型。记录大鼠从迷宫起点游到终点所需要的时间和途中进入盲端的错误次数,作为衡量大鼠学习记忆能力的指标,选取百会、涌泉穴位等进行电针治疗。结果发现穹隆—海马损伤后严重影响到大鼠的学习记忆能力。经电针治疗后,电针组大鼠的平均终点游出时间与平均错误次数均较模型组明显减少,呈极显著性差异。结论电针刺激能有效改善老年痴呆的智力障碍,提高学习记忆能力。

牛磺酸对急性染锰大鼠空间学习记忆能力的改善作用

目的探讨急性染锰对大鼠学习记忆能力的影响及牛磺酸的干预作用。方法 (1)牛磺酸预防实验:染锰组大鼠每日ip给予MnCl2.4H2O15 mg·kg-1,连续4周。染锰+牛磺酸预防组大鼠染锰的同时ip牛磺酸200 mg·kg-1,持续4周。(2)牛磺酸治疗实验:每日ip给予MnCl2.4H2O15 mg·kg-1染锰,4周后再ip牛磺酸200 mg·kg-1,持续4周。水迷宫实验检测逃避潜伏时间及平台搜索次数。分离大鼠海马组织并测定乙酰胆碱酯酶(AChE)活力及胆碱O-乙酰转移酶(ChAT)活力。结果 (1)牛磺酸预防实验:与正常对照组逃避潜伏时间(29.5±2.5)s相比,染锰对照组明显延长为(39.8±2.3)s,与染锰对照组相比,牛磺酸预防组逃避潜伏时间明显缩短为(29.4±2.3)s(P<0.05)。与正常对照组相比,染锰对照组海马组织AChE活力无显著性差异,但牛磺酸预防组酶活力则显著下降(P<0.05)。三组间ChAT活力无明显差异。(2)牛磺酸治疗实验:与染锰对照组逃避潜伏时间(56.6±3.0)s相比,牛磺酸治疗组显著缩短为(27.8±2.3)s(P<0.05),平台搜索次数无显著性差异。与染锰对照组AChE和ChAT活力显著增加(P<0.05)。结论牛磺酸预防或治疗可明显改善急性染锰诱导大鼠空间学习记忆能力下降,其机制可能与海马内乙酰胆碱含量有关。

铝过负荷致小鼠脑神经元退变与脑铁代谢失衡的关系

目的探讨铝致神经元退行性变是否与脑铁代谢失衡有关。方法每只鼠侧脑室内分别注射0．125％，0．25％和0．5％的Al溶液3μL（AlCl3·6H2O配制，以Al计算浓度），每日1次，连续5d（d1—d5），建立铝过负荷小鼠模型。于d10，d20和d30用跳台法和水迷宫测定小鼠学习记忆能力、海马病理形态学改变、海马单胺氧化酶B（MAO—B）活性、海马线粒体铁蛋白水平和全脑铁水平。结果铝过负荷致小鼠学习记忆能力明显下降，海马CAl区神经元核固缩和神经细胞丢失，脑内铁水平明显升高，海马线粒体内铁蛋白水平明显降低、MAO—B活力显著升高．均呈剂量依赖性和时间依赖性改变。结论铝过负荷致神经元退变可能与其干扰脑铁代谢有关.

血管性痴呆大鼠记忆障碍与海马Bcl-2蛋白表达的研究

目的 :探讨Bcl- 2参与血管性痴呆 (VD)大鼠学习记忆障碍的作用机制。方法 :采用 4 -血管阻断的方法 ,复制大鼠VD模型 ,用免疫组化法检测海马Bcl- 2蛋白表达水平的变化 ;并用Nissl染色方法 ,结合图象分析统计海马神经元丢失比率 ;同时采用Y -型迷宫 ,进行行为学检测 ,定量测定其学习记忆成绩。结果 :在VD大鼠空间分辩发生严重障碍时 ,海马CA1、CA3 、DG区神经元丢失比率高于对照组 ,同时Bcl- 2蛋白表达水平高于对照组。结论 :Bcl- 2抑制细胞凋亡 ,对VD大鼠海马神经元起保护作用 ,减轻VD大鼠学习记忆障碍。

癫癎后学习记忆障碍大鼠海马中脑源性神经营养因子表达的变化

目的:探讨戊四氯(pentylenetetrazole,PTZ)化学点燃癫癎大鼠在Y迷宫中学习记忆能力与海马脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)mRNA和蛋白质表达变化的关系,以期为研究癫癎患者的记忆损害及其治疗提供线索。方法:成年健康雄性SD大鼠随机分为癫癎持续状态(status epilepticus,SE)组、SE对照组、慢性癫癎(chronic epi- lepsy,CEP)组和CEP对照组。SE模型按40 mg/kg腹腔注射PTZ溶液.10 min后注射20 mg/kg,然后每10 min注射10 mg/ kg,直至诱发大鼠癫癎持续状态发作。CEP模型按35 mg/kg腹腔注射PTZ溶液,每48 h一次,直到连续3次RacineⅣ～Ⅴ级癎性发作。对照组与相应模型组同时腹腔注射同等容量的生理盐水。用交替电刺激Y迷宫试验检测大鼠学习记忆能力,采用RT-PCR和免疫组织化学法检测大鼠海马BDNF mRNA和蛋白质的表达变化。结果:交替电刺激Y迷宫试验中,SE组大鼠与SE对照组相比致癎后1d和2d的选择错误总数明显增加(P<0.05);CEP组致癎后1 d、30 d、31 d的选择错误总数与CEP对照组相比均有明显增加(P<0.05)。在海马中,致癎后1 d的SE组和CEP组以及致癎后30 d的CEP组BDNF mRNA和蛋白质表达水平均较低。结论:癫癎持续状态可导致大鼠短时间的学习记忆功能受损,而慢性癫癎引起的学习记忆能力损伤持续时间较长。癫癎所致的学习记忆功能障碍可能与海马BDNF的表达减少有关。