慢性应激抑郁大鼠海马CA1神经元突触可塑性研究

目的 探讨慢性轻度不可预见应激(chronic unpredictable mild stress,CUMS)抑郁模型大鼠海马CA1区神经元的突触可塑性改变.方法 将20只雄性Sprague-Dawley (SD)大鼠随机等分为CUMS组和对照组,前者连续28天每天随机接受不同的应激,对照组同样条件下饲养但不给应激,至第28天进行行为测评后处死,在日立(H7500)透射电镜下测量海马CA1神经元突触界面结构参数.结果 CUMS抑郁大鼠海马CA1神经元突触活性区长度(216.64±20.19 nm)及突触后致密物厚度(42.4±5.23 nm)显著小于对照组(321.58±12.27nm,69.6±4.77 nm),差异有统计学意义(P＜0.05),突触界面曲率及宽度与对照组差异无统计学意义(P＞0.05).结论 慢性应激性抑郁大鼠存在海马CA1区神经元突触可塑性的改变.这提示抑郁症的发病机制可能与海马神经元突触可塑性相关.     

吗啡戒断后焦虑症状大鼠伏核和杏仁核突触结构可塑性

目的 探讨吗啡依赖戒断焦虑行为与大鼠伏核、杏仁核突触形态结构可塑性变化之间的相关性.方法 采用剂量递增法建立大鼠吗啡依赖模型,应用高架十字迷宫检测焦虑行为,应用透射电镜技术结合图像分析系统比较对照组、模型组和治疗组(每组均6只)大鼠伏核、杏仁核突触体视学、界面结构参数的数据.结果 (1)行为学:模型组开放臂的次数和时间均少于对照组和治疗组(P＜0.01或P＜0.05).(2)突触体视学:伏核模型组数密度(Nv)[(1.012±0.036)个/μm3]较对照组[(0.701±0.138)个/μm3]和治疗组[(0.751±0.245)个/μm3]增加(P＜0.01),面密度(Sv)和突触连接带平均面积(S)3组间比较差异无统计学意义;杏仁核模型组Nv[(0.427±0.178)个/μm3]较对照组[(0.247±0.117)个/μm3]和治疗组[(0.246±0.116)个/μm3]增加(P＜0.01或P＜0.05),模型组Sv[(0.047±0.018)μm2/μm3]较对照组[(0.030±0.012)μm2/μm3]和治疗组[(0.030±0.015)μm2/μm3]增加(P＜0.01),模型组S[(0.124±0.066)μm2]较对照组[(0.157±0.119)μm2]和治疗组[(0.159±0.114)μm2]减小(P＜0.05).(3)突触界面结构:伏核和杏仁核各自突触的突触后致密物厚度、突触活性区长度、突触间隙宽度和突触界面曲率在模型组、对照组和治疗组间比较差异均无统计学意义.结论 吗啡依赖戒断所产生的焦虑与伏核和杏仁核突触形态结构可塑性的改变有一定相关性.

Abstract：

Objective The possible correlations between morphological contracture and plastic variability of synaptic structure in nucleus accumbens and amygdala neurons were surveyed in anxious symptom rats suffered from morphine withdrawal. Methods The escalating doses of morphine and the elevated plus-maze were applied to validate anxiety-like behavior in rats. The electron microscope was applied to detect the parameters involving the synaptic stereology and structural plasticity of synaptic interface structure of the nucleus accumbens and amygdala neurons in the control group, the morphine-withdrawal group and the cured group ( n = 6 ), associated with the stereological ways. Results ( 1 ) Compared with the control group and the cured group, reductions of frequency and time of open-arm were observed in the morphine-withdrawal group ( P ＜ 0. 01 or P ＜ 0. 05 ). ( 2 ) Higher numerical density ( Nv ) [( 1. 012 ±0. 036 )/μm3] of synapses of nucleus accumbens was detected in the anxious rats ( P ＜ 0. 01 ) than in the controls [( 0. 701 ±0. 138 )/μm3] and the cured rats [( 0. 751 ±0. 254 )/μm3] . No significant difference between the surface density ( Sv ) and the mean profile area ( S ) of synapse of the nucleus accumbens was discovered. Compared with the control group [( 0. 247 ± 0. 117 )/μm3] and the cured one [( 0. 246 ±0. 116 )/μm3] , higher values of Nv [( 0. 427 ±0. 178 )/μm3] in amygdala were detected in anxious rats ( P＜0.01 or P＜0.05 ). Similarly, higher score of Sv [( 0.047 ±0.018 )μm2/μm3] in amygdala was observed in the anxious rats ( P ＜ 0. 01 ) than those of the control group [( 0. 030 ±0. 012 )μm2/μm3] and cured group [( 0. 030 ±0. 015 )μm2/μm3] . However, anxious rats [( 0. 124 ±0. 066 )μm2] appear to be lower S of synapse in amygdale ( P ＜ 0. 05 ) than those of the control group [( 0. 157 ±0. 119 )μm2] and the cured group [( 0. 159 ±0. 114 )μm2] . ( 3 )No significant difference among postsynaptic density, length of synaptic thickening, widths in synaptic interface structure on junctions and curvature of synaptic cleft region was detected in the nucleus accumbens and amygdala neurons. Conclusion In the present study, the results suggest that anxious rats suffered from morphine withdrawal could possibly be related to the plastic variability of synaptic morphological structure in nucleus accumbens and amygdale.     

丁基苯酞对慢性脑缺血老龄大鼠海马中NMDA受体亚单位NR2B及突触素表达的影响

目的 观察丁基苯酞对慢性脑缺血老龄大鼠海马中N-甲基-D-天门冬氨酸受体2B亚单位(NR2B)及突触素表达的影响.方法 采用免疫组化方法观察丁基苯酞对慢性脑缺血老龄大鼠海马中NR2B及突触素表达的影响.结果 B组与A组比较,海马CA1区、CA3区及齿状回NR2B及突触素的表达明显减少(P＜0.05),C、D组大鼠海马各区NR2B及突触素的表达与单纯缺血组比较均不同程度增加(P＜0.05);D组与C组比较,NR2B及突触素的表达增加更明显(P＜0.05).结论 慢性缺血3个月后,大鼠海马CA1区、CA3区及齿状回中NR2B 及突触素的表达明显减少,而丁基苯酞能改善这种缺血改变,增加NR2B 及突触素的表达.     

慢性脑缺血老龄大鼠海马中突触素的表达特征

目的 研究老龄大鼠慢性脑缺血后大脑海马中突触素表达特征.方法 应用免疫组化染色技术检测大鼠脑海马中CA1区、CA3区和齿状回中突触素的表达.结果 缺血组海马CA1区、CA3区和齿状回三处突触素灰度值均低于对照组,差异有统计学意义(P<0.05.结论 老龄大鼠海马结构内CA1区、CA3区及齿状回内突触素和NR2B的表达明显减少.     

小鼠衰老性记忆障碍的脑内突触形态学变化

本文定且研究了小鼠的海马CA3区和大脑皮层感觉运动区GrayⅠ型突触界面结构。衰老小鼠按一次性被动回避反应检测结果分成记忆宪好组和记忆衰退组，两组的统计比较结果表明：记忆衰退组突触后致密物质厚度极显著变小（在海马，P＜0．01；在皮层，P＜0．001）；海马CA3区突触活性带长度极显著变短（P＜0．01）；而上述两脑区突触间隙宽度则极显著增大（P＜0．01）；海马CA3区的正向弯曲型突触数显著减少，平坦型突触数显著增多（P＜0．05）．     

三磷酸胞苷二钠对脑缺血大鼠海马CA3区突触体素表达的影响

目的　研究局灶性脑缺血后海马 CA3 区突触体素的动态表达及其三磷酸胞苷二钠对其干预的影响。方法　选取 SD大鼠 60只 ,随机分为脑缺血后自然恢复组、药物干预组和假手术对照组。采用线栓法建立大脑中动脉脑缺血大鼠模型 ,应用免疫组化技术观察海马 CA3 区突触体素的表达。结果　脑缺血后自然恢复组大鼠突触体素的表达较对照组明显降低 (P<0 .0 1) ;但 7～ 2 1d突触体素的表达逐渐上调 (P<0 .0 1)。应用三磷酸胞苷二钠干预后 ,突触体素表达与自然恢复组相比明显升高。结论　脑缺血损伤后海马 CA3 区突触体素表达减少 ,但机体自身存在着神经元的修复和再生 ;三磷酸胞苷二钠可上调突触体素的表达 ,具有促进缺血神经元的修复、再生及突触重塑作用。     

经颅磁刺激对脑梗死大鼠学习记忆与健侧海马锥体细胞树突和突触结构的影响

目的研究经颅磁刺激(TMS)对脑梗死后大鼠学习记忆功能,以及海马锥体细胞树突和突触结构的影响。方法将48只雄性SD大鼠随机分为正常组、模型组和TMS组,每组16只。采用线栓法对模型组和TMS组大鼠制作一侧大脑中动脉闭塞的脑梗死模型,并在制模后第2天,对TMS组给予每天2次、每次30个脉冲的TMS治疗,疗程4周;观察各组大鼠治疗后在Y-迷宫中的学习记忆成绩和梗死对侧海马锥体细胞树突和突触结构变化。结果(1)TMS组大鼠学习尝试次数[(18.4±4.8)次]少于模型组[(26.4±5.4)次;P<0.01],记忆再现次数[(6.1±1.3)次]多于模型组[(3.7±1.2)次;P<0.01];(2)TMS组海马CA3区锥体细胞树突顶树突总长度[(196±35)μm]长于模型组(175±33)μm;P<0.01]。(3)TMS组的突触后致密物质厚度[(68±11)nm]宽于模型组[(62±10)nm],穿孔性突触百分比(27.5%)高于模型组(10.0%),突触间隙[(16.7±1.8)nm]窄于模型组[(21.3±2.3)nm],均P<0.01和P<0.05。结论TMS能促进脑梗死大鼠学习记忆功能的恢复,其机制可能与海马锥体细胞树突和突触结构的改变有关。     

褪黑素对阿茨海默病大鼠海马突触素表达的影响

目的 研究褪黑素(melatonin,MT)对阿茨海默病(Alzheimer's disease , AD)大鼠的海马突触素表达的影响.方法 大鼠随机分为4组,分别为AD组、AD-MT大剂量干预组、AD-MT小剂量干预组和假AD组.应用β-淀粉样蛋白(Aβ)注入大鼠海马CA1区,建立大鼠AD模型,AD-MT干预组随之以MT灌胃,1次/d,直至试验结束.应用电迷宫检测大鼠学习记忆情况,用免疫组化方法检测大鼠海马CA1区突触素的表达情况.结果 MT可以明显改善AD大鼠的学习记忆能力,提高大鼠海马CA1区突触素的阳性表达.结论 MT对AD大鼠有显著脑保护作用.     

颞叶癫痫大鼠海马CA1区突触可塑性与空间记忆能力关系的研究

目的探讨颞叶癫痫大鼠海马CA1区突触超微结构与空间记忆能力改变的关系。方法以海人酸杏仁核微量注射建立经典的雄性Wistar大鼠颞叶癫痫化学点燃模型,分别于点燃后11d、17d、21d测定大鼠的空间记忆能力,并观察第21d海马CA1区神经毡突触超微结构变化。结果颞叶癫痫大鼠空间记忆能力减低,同时伴有海马CA1区神经毡内突触数密度降低(P<0．05),突触活性区膜面积缩小(P<0．05),突触界面曲率降低(P< 0．05),比表面减小(P<0．05),突触小泡数密度降低(P<0．05)。结论颞叶癫痫大鼠海马CA1区神经毡内突触损害和活力可能是导致其空间记忆能力下降的重要机制。     

甘露醇对骨髓间充质干细胞治疗血管性痴呆大鼠行为学及海马CA3区突触素表达水平的影响

目的 探讨甘露醇预处理对骨髓间充质干细胞(bone marrow mesenchymal stromal cells,BMSCs)静脉移植治疗血管性痴呆(vascular dementia,VD)模型大鼠行为学及海马CA3区突触素表达的影响.方法 以全骨髓贴壁法培养大鼠BMSCs.采用间隔3d双侧颈总动脉永久性结扎法制备VD模型,设立假手术组.造模4周后将VD大鼠按随机数字表法分为模型组、培养基组、甘露醇组、BMSCs组、甘露醇预处理BMSCs组,分别给予相应的实验干预措施.观察干预4周后实验大鼠的行为学表现及应用免疫组织化学法检测海马CA3区突触素的表达水平.结果 甘露醇预处理BMSCs组行为学表现较其他实验组有明显改善,其第5天逃避潜伏期(s)比BMSCs组、模型组、培养基组、甘露醇组明显缩短(9.3±2.9,14.1±3.5,23.5士4.4,22.8±4.4,23.2±2.8,F=43.900,P=0.000),平台象限滞留时间(s)比BMSCs组、模型组、培养基组、甘露醇组明显延长(40.8±6.3,34.9 ±5.8,26.4 ±4.8,27.4±7.0,28.5±6.2,F=13.000,P=0.000),其海马CA3区突触素表达水平(39 624±7798)亦比BMSCs组、模型组、培养基组、甘露醇组明显提高(27 060±4668,18 294±6446,19 956±4244,18 946±4953,F=39.206,P=0.000).结论 甘露醇预处理后静脉移植BMSCs显著改善VD大鼠行为学表现,并使其海马CA3区突触素表达增加.甘露醇预处理明显提高静脉移植BMSCs治疗VD大鼠的效果.     

Effects of movement training on synaptic interface structure in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere in cerebral infarction rats★

BACKGROUND： Movement is an effective way to provide sensory, movement and reflectivity afferent stimulation to the central nervous system. Movement plays an important role in functional recombination and compensation in the brain. OBJECTIVE： To observe movement training effects on texture parameters of synaptic interfaces in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere and on motor function in cerebral infarction rats. DESIGN, TIME AND SETTING： This neural morphology and pathology randomized controlled animal experiment was performed at the Center Laboratory, Affiliated Hospital of Luzhou Medical College, China from November 2004 to April 2005. MATERIALS： A total of 32 healthy male Wistar rats aged 8 weeks were equally and randomly assigned into model and movement training groups. METHODS： Rat models of right middle cerebral artery occlusion were established using the suture occlusion method in both groups. Rats in the movement training group underwent balance training, screen training, and rotating rod training starting on day 5 after surgery, for 40 minutes every day, 6 days per week, for 4 weeks. MAIN OUTCOME MEASURES： Texture parameters of synaptic interfaces were determined using a transmission electron microscope and image analyzer during week 5 following model induction. The following parameters were measured： synaptic cleft width; postsynaptic density thickness; synaptic interface curvature; and active zone length. Motor function was assessed using balance training, screen training, and rotating rod training. The lower score indicated a better motor function. RESULTS： The postsynaptic density thickness, synaptic interface curvature, and active zone length were significantly increased in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere of rats from the movement training group compared with the model group （P 〈 0.05 or 0.01）. Curved synapses and perforated synapses were seen in the sensorimotor cortex and hippocampal CA3 area at     

Effects of movement training on synaptic interface structure in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere in cerebral infarction rats

BACKGROUND:Movement is an effective way to provide sensory,movement and reflectivity afferent stimulation to the central nervous system. Movement plays an important role in functional recombination and compensation in the brain. OBJECTIVE: To observe movement training effects on texture parameters of synaptic interfaces in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere and on motor function in cerebral infarction rats. DESIGN,TIME AND SETTING: This neural morphology and patholog...     

The effect of chronic thienorphine administration on long‐term potentiation and synaptic structure in rat hippocampus

Thienorphine is a new nonselective partial agonist of opioid receptors, which is currently under a Phase II clinical trial in China as a new treatment for opioid dependence. In this study, we compared the effect of thienorphine with morphine on long‐term potentiation (LTP) in the lateral perforant path (LPP)‐granule cell synapse of the rat dentate gyrus (DG). Furthermore, the effect of thienorphine on the synaptic structure of the CA1 hippocampal region and the expression of synaptophysin was investigated. Results indicated interesting differences between thienorphine and morphine on the modulation of hippocampal synaptic plasticity. Chronic thienorphine treatment facilitated LTP in the LPP‐DG cell synapses more than chronic morphine treatment. Morphometric measurement and analysis showed that chronic thienorphine administration decreased the length of the active zone and reduced the thickness of CA1 postsynaptic densities compared with the saline group (control), but were elevated compared with the morphine group. Furthermore, the expression of hippocampal synaptophysin was increased with chronic thienorphine administration but reduced with chronic morphine treatment. Taken together, our study clearly demonstrates that chronic thienorphine treatment enhances LTP, modulates hippocampal synaptic structure, and increases the expression of hippocampal synaptophysin. Therefore, further study is warranted to investigate thienorphine as a new treatment for opioid dependence. Synapse 67:779–785, 2013 . © 2013 Wiley Periodicals, Inc.     

Dietary cholesterol alters memory and synaptic structural plasticity in young rat brain

Cholesterol plays an important role in synaptic plasticity, learning and memory. To better explore how dietary cholesterol contributes to learning and memory and the related changes in synaptic structural plasticity, rats were categorized into a regular diet (RD) group and a cholesterol-enriched diet (CD) group, and were fed with respective diet for 2 months. Dietary cholesterol impacts on learning and memory, hippocampal synaptic ultrastructure, expression levels of postsynaptic density-95 (PSD-95), synaptophysin (SYP) and cannabinoid receptor type 1 (CB1R) were investigated. We found CD rats had better performances in learning and memory using Morris water maze and object recognition test than RD rats. The memory improvement was accompanied with alterations of synaptic ultrastructure in the CA1 area of the hippocampus evaluated by electron microscopy, enhanced immunoreactivity of SYP, a presynaptic marker in hippocampus detected by immunocytochemistry, as well as increased levels of PSD-95, SYP and decreased level of CB1R in brains of CD rats determined by Western blot. Taken together, the results suggest that the improvement of learning and memory abilities of the young adult rats induced by dietary cholesterol may be linked with changes in synaptic structural plasticity in the brain.     

创伤性癫痫大鼠前脑海马CA3区突触蛋白表达与突触重建的相关性

摘要 目的：动态观察突触后密度蛋白-95(PSD-95)和突触囊泡蛋白(SYN)在外伤性癫痫(PTE)大鼠前脑的表达,探讨有关发病机制。方法：立体定向注射1000 nmol FeCl2：于大鼠右侧运动皮层致痫,在不同时间点行为学视频、脑电图监测,用免疫组织化学法检测24h、7d、14d、21d、30d大鼠前脑内PSD-95及SYN的表达。结果;所有大鼠在注射FeC12后不久记录到癫痫样放电,7d达高峰;致痫后24h即可见前脑神经元PSD-95表达下降,7d达最低值,14d后回升;SYN表达在24h明显下降,7d后逐渐回升。结论：FeC12皮层注射可以制成PTE动物模型。与PSD-95 及SYN表达相关的神经元及胶质细胞的动态变化在PTE的发病机制中起重要作用。PSD-95和SYN表达减少可能为FeCl2致痫的共同途径。     

针刺结合运动训练干预脑梗死大鼠海马CA3区微管相关蛋白及突触素表达及学习记忆功能变化

实验观察针刺百会(GV20)、曲鬓(GB 7)和前顶穴(GV21)联合运动训练干预和件下大脑中动脉闭塞大鼠模型大鼠海马CA3区微管相关蛋白2和突触素蛋白的表达,并和单独运动训练干预的大鼠对比。Y型迷宫实验和免疫组织化学染色显示,建模后5周,针刺联合运动训练组穿越Y型迷宫错误次数均少于模型组和运动训练组,针刺联合运动训练组的微管相关蛋白2和突触素表达明显增高,各组海马CA3区的微管相关蛋白2,突触素的表达和穿越Y型迷宫错误次数均呈明显的负相关性。说明针刺联合运动训练可以改善脑梗死大鼠学习和记忆功能,其机制与海马CA3区的树突及突触可塑性有关。     

Impaired hippocampal memory function and synaptic plasticity in experimental cortical dysplasia

Purpose: Memory impairment is a common comorbidity in people with epilepsy‐associated malformations of cortical development. We studied spatial memory performance and hippocampal synaptic plasticity in an animal model of cortical dysplasia. Methods: Embryonic day 17 rats were exposed to 2.25 Gy external radiation. One‐month‐old rats were tested for spatial recognition memory. After behavioral testing, short‐term and long‐term synaptic plasticity in the hippocampal CA1 region was studied in an in vitro slice preparation. Key Findings: Behavioral assessments showed impaired hippocampal CA1‐dependent spatial recognition memory in irradiated rats. Neurophysiologic assessments showed that baseline synaptic transmission was significantly enhanced, whereas paired‐pulse facilitation, long‐term potentiation, and long‐term depression of the field excitatory postsynaptic potential (fEPSP) slope at Schaffer collateral/commissural fiber‐CA1 synapses were significantly reduced in the irradiated rats. Histologic observations showed dysplastic cortex and dispersed hippocampal pyramidal neurons. Significance: This study has shown that prenatally irradiated rats with cortical dysplasia exhibit a severe impairment of spatial recognition memory accompanied by disrupted short‐term and long‐term synaptic plasticity and may help to guide development of potential therapeutic interventions for this important problem.     

Downregulation of caveolin-1 contributes to the synaptic plasticity deficit in the hippocampus of aged rats

Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its ex-pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebellum of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged （22-24 month old） rats was significantly lower than that in young （1 month old） and adult （4 months old） rats. Ex- pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebellum. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebellum. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging.