慢性复合应激增强大鼠空间学习和记忆能力

本文观察了慢性复合应激对大鼠学习与记忆功能的影响。实验采用成年 Wistar 大鼠, 将其随机分成应激组和对照组。采用垂直旋转、睡眠剥夺、噪音刺激和夜间光照4 种应激原, 无规律地交替刺激动物 6 周, 每天6 h, 制作慢性复合应激动物模型。采用 Morris 水迷宫和 Y- 迷宫测试大鼠学习与记忆成绩,并用 Cresyl violet 染色法对大鼠海马结构进行神经细胞计数。结果显示,应激组动物慢性复合应激后, 在 Morris 水迷宫内寻找隐蔽平台所需的时间(潜伏期)比对照组的明显地短(P<0.05), 表明应激鼠的空间记忆能力明显强于对照鼠;在 Y- 迷宫内寻找安全区的正确率比对照组的明显地高(P<0.05), 表明应激鼠的明暗分辨学习能力明显强于对照鼠; 应激鼠慢性复合应激后, 其海马结构齿状回、CA3 和CA1 区神经细胞密度极明显地高于对照鼠(P<0.001)。这些结果提示, 慢性复合应激可增强大鼠空间记忆能力和明暗分辨学习能力。本文并对慢性复合应激模式增强大鼠学习和记忆能力的可能原因进行了讨论。     

短途运输应激对Wistar大鼠的影响

目的研究短途运输应激对Wistar大鼠的影响,建立评价啮齿类实验动物短途运输应激的技术指标体系。方法采用Wistar大鼠进行短途运输实验,测定其在运输中及运输后各阶段的代谢、神经内分泌和免疫功能主要指标,与未经历运输的对照组比较,分析短途运输应激的影响。结果Wistar大鼠血糖（GLU）在运输0.5 h和1 h时均升高,而在运输1.5 h时降低,运输结束后24 h时GLU再次升高;血清皮质酮（CORT）亦在运输0.5 h和1h时升高而运输1.5 h时降低,但运输结束24 h起即恢复正常;血清β-内啡肽（-βEP）从运输起至运输结束24 h时均降低,至48 h恢复正常。外周白细胞总数（WBC）自运输起急剧减少,于结束运输后的72 h恢复;免疫球蛋白G（IgG）、白介素2（IL-2）、γ干扰素（IFN-γ）及白介素1（IL-1）的血清水平在运输中及运输结束的即刻均没有显著变化,但在结束运输后的48 h内均不同程度降低,至72 h恢复至正常水平。肝脏hsp72 mRNA的表达随着运输时间的延长而极显著上调,运输结束后逐渐恢复,至72 h恢复至正常水平。结论短途运输应激对Wistar大鼠的代谢、神经内分泌和免疫功能均有不利影响,其经历常规短途运输（1.5 h以内）到达目的地后的健康适应期至少应为72 h;外周血中白细胞总数（WBC）、血糖（GLU）、皮质酮（CORT）、β-内啡肽（-βEP）、白介素2（IL-2）的水平可用于系统评价短途运输应激。     

逍遥散对慢性束缚应激模型大鼠相关脑区CRF基因表达的影响

目的:观察慢性束缚应激大鼠相关脑区CRF mRNA(下丘脑、垂体、海马、皮层)含量变化以及逍遥散对其影响.方法:用RT-PCR和图像分析方法测定相关脑区CRF mRNA含量变化.结果:应激组较正常对照组在下丘脑CRF-1基因表达下调(P<0.01).在下丘脑逍遥散组较应激组CRF-1基因表达显著下调(P<0.01),CRF-2基因表达显著上调(P<0.01);在海马区逍遥散组CRF-2基因表达较模型组上调(P<0.05);在皮层逍遥散组CRF-1基因表达较应激组则显著上调(P<0.01).结论:逍遥散组对慢性束缚应激中枢神经肽CRF的调节位点在下丘脑、垂体、海马和皮层,充分证实逍遥散的调节靶点与下丘脑、边缘系统及皮层中枢有关.     

不同时程束缚水浸应激对大鼠胃排空的影响

目的研究不同时程慢性束缚水浸应激对大鼠胃排空的影响。方法48只雄性150 g左右SD大鼠被随机分为6组,即实验3、72、8 d组和对照3、72、8 d组,每组8只。实验期间,每日观察大鼠体重、一般状况及行为学指标。实验组23℃水域箱内束缚水浸1 h/d,对照组自由摄食饮水。采用半固体排空实验（阿拉伯胶炭糊）来检测胃排空率,数据录入SPSS 13.0进行分析处理。结果①体重增加情况：不同组别和不同应激时间这两个因素对体重增加的影响差异均有显著性。②胃排空率：对照各组间比较均无统计学差异。3 d组间（实验3d组与对照3 d组）大鼠胃排空率无差异;而7 d组间和28 d组间比较则明显异常。随着应激时间的延长,实验组胃排空率呈现了先增高（7 d时）后降低（28 d）的变化趋势,且实验3 d组与7 d组、7 d组与28 d组间比较均有明显的统计学意义,而3 d组与28 d组比较则无统计学差异。结论不同时程的慢性束缚水浸应激可以导致大鼠胃排空率改变;随着应激时间的延长,呈现先上升后下降的规律。     

艾灸干预不同穴位对束缚应激模型大鼠心理行为改变的影响

目的:观察艾灸不同穴位对束缚应激模型大鼠行为学改变的影响,进一步探讨艾灸对束缚应激所致心理行为改变的作用规律。方法:将35只雄性Wistar大鼠按分层随机法分为正常组、束缚应激模型组、艾灸百会(GV20)组、艾灸关元(CV4)组、艾灸足三里(ST36)组,每组各7只。除正常组外,余各组均采用自制布袋束缚大鼠30 min,每日1次,共20次,制备束缚应激大鼠模型,于造模第2天各治疗组捆绑固定后给予艾炷灸3壮,正常组及模型组捆绑束缚20 min,隔日一次,共10次。于造模前、造模后,治疗5次、10次分别采用高架十字迷宫检测各组大鼠开放臂进入次数比例(OE%)及开放臂停留时间比例(OT%)的变化。结果:①与造模前比较,艾灸百会(GV20)组大鼠造模后、治疗10次后OE%均降低明显,治疗5次后OT%升高明显,均有显著性差异(P<0.05),艾灸关元(CV4)组大鼠造模后OT%降低明显,有显著性差异(P<0.05),艾灸足三里(ST36)组大鼠造模后OE%和OT%、治疗10次后OE%均明显降低,均有显著性差异(分别为P<0.05,P<0.05,P<0.01);与造模刚结束比较,艾灸百会(GV20)组大鼠治疗5次后OE%与OT%均升高明显,均有显著性差异(P<0.05),艾灸关元(CV4)组大鼠治疗10次后OT%升高明显,有显著性差异(P<0.01),艾灸足三里(ST36)组大鼠治疗5次后OE%、治疗10次后OT%均明显升高,有显著性差异(分别为P<0.01,P<0.05);与治疗5次比较,艾灸百会(GV20)组、足三里(ST36)组大鼠治疗10次后OE%明显降低,艾灸关元(CV4)组大鼠治疗10次后OE%和OT%升高明显,均有显著性差异(P<0.05)。②与艾灸百会(GV20)组比较,艾灸关元(CV4)组与艾灸足三里(ST36)组大鼠在治疗5次、10次后OE%和OT%呈不同程度的升高或降低趋势,未见显著性差异(P>0.05)。结论:艾灸不同穴位可一定程度改善慢性束缚应激所致大鼠焦虑心理行为的变化;关元(CV4)、百会(GV20)、足三里(ST36)三穴均表现出一定抗焦虑效应,百会(GV20)穴在治疗早期效果显著,足三里(ST36)穴的疗效肯定,而关元(CV4)穴在长期治疗中效应更为稳定、明显,具有相对特异性。     

杏仁核SIRT1对慢性束缚应激大鼠抑郁样行为的影响

目的:观察杏仁核沉默信息调节因子1(SIRT1)蛋白对慢性束缚应激(CRS)大鼠抑郁样行为的影响。方法:60只SD雄性大鼠随机分为6组(n=10):正常对照组(Control)、慢性束缚应激组(CRS)、CRS+氟西汀(FLU)组(CRS+FLU)、CRS+生理盐水组(CRS+NaCl)、CRS+SIRT1过表达组(CRS+AAV-SIRT1)和CRS+空载体组(CRS+AAV-EGFP)。除了正常对照组,其余各组均接受慢性束缚应激造模21 d。造模结束后,氟西汀组和生理盐水组大鼠每天分别灌胃给予氟西汀(10 mg/kg)或生理盐水(10 mg/kg),持续3周;SIRT1过表达组和空载体组大鼠分别脑立体定位,注射腺相关病毒AAV-SIRT1或AAV-EGFP于杏仁核,待病毒表达3周;正常组和抑郁症组大鼠则不给予任何药物。应用糖水偏好实验(SPT)、旷场实验(OFT)和强迫游泳实验(FST)检测各组大鼠的抑郁样行为学变化;蛋白免疫印迹实验检测大鼠杏仁核中SIRT1蛋白的表达;免疫荧光技术检测大鼠杏仁核中SIRT1阳性细胞数量。结果:与正常对照组相比,CRS抑郁大鼠杏仁核中SIRT1蛋白...     

束缚应激对大鼠同型半胱氨酸代谢的影响

为了探讨束缚应激对大鼠血清含硫氨基酸代谢的影响,根据同型半胱氨酸(Hcy)水平,将32只雄性Wistar大鼠分为对照组(control)、束缚应激组(RS)、1%蛋氨酸组(1%Met)和1%蛋氨酸+束缚应激组(1%Met+RS)。采用高压液相色谱法检测血清中的Hcy、半胱氨酸(Cys)和还原型谷胱甘肽(GSH)含量,采用全自动氨基酸分析仪测定血清中蛋氨酸(Met)和牛磺酸(Tau)含量。结果显示,RS组大鼠血清Hcy、Cys和GSH含量随着束缚时间延长而降低,且较对照组和1%蛋氨酸组有显著性差异(p<0.05);RS组大鼠血清Met和Tau含量较对照组和1%蛋氨酸组则显著升高(p<0.05)。束缚应激可能降低血清抗氧化能力和总Hcy水平。     

慢性应激对大鼠学习记忆能力和海马LTP的影响

目的和方法：本研究采用一种多因素的２１ｄ慢性应激动物模型,以Ｙ迷宫和ＬＴＰ为指标,探讨慢性应激对运动学习记忆能力和海马神经突触可塑性的影响。结果：长期慢性应激使大鼠空间学习记忆能力下降,而且,使中枢海马齿状回ＬＴＰ的诱生受到抑制。结论：慢性应激可能使大鼠海马齿状回神经突触可塑性降低,并进一步影响到学习记忆的功能。     

束缚应激对大鼠心肌细胞凋亡的影响及中药颐心宁的干预作用

目的 :探讨束缚应激对大鼠心肌细胞凋亡的影响及中药颐心宁抗应激性心肌损伤的作用。方法 :采用琼脂糖凝胶电泳和TUNEL检测心肌细胞凋亡。结果 :①束缚 1、2、4周时 ,应激组DNAladder心肌细胞凋亡结果阴性 ,原位细胞凋亡明显增多 ,统计学有非常显著差异 (P <0 .0 1) ;②颐心宁干预组DNAladder结果阴性 ,而原位细胞凋亡检测结果则较单纯应激大鼠显著减轻 (P <0 .0 5 ) ;③蒸馏水干预组与单纯应激大鼠比较则无统计学意义 (P >0 .0 5 )。结论 :束缚应激可诱导大鼠心肌细胞发生凋亡 ,中药颐心宁可抑制心肌细胞凋亡 ,具有抗应激性心肌损伤的作用。     

高压氧预处理对SPS暴露大鼠学习记忆能力以及海马神经元凋亡的影响

目的:研究高压氧(HBO)预处理对SPS暴露大学学习记忆能力及其大脑海马神经元细胞凋亡的影响.方法:48只雄性Sprague-Dawley大鼠(体重220-260 g)随机分为4组(n=12):对照(sham)组,高压氧(HBO)组,SPS组以及高压氧+SPS组.高压氧组每天1小时高压氧预处理(2.5个大气压,100%O2)连续5天;SPS组采用单次延长应激模型;高压氧+SPS组每天l小时高压氧预处理连续5天于最后一次预处理后24小时,制作SPS模型.4组大鼠于SPS暴露后72小时进行TUNEL染色,第15天经行水迷宫测试.结果:水迷宫实验中大鼠逃避潜伏期及游泳路径四组之间有明显统计差异[F0.01(3,28)=4.88＞4.57,P＜0.01;F0.01(3,28)=5.31＞4.57,P＜0.01].SPS组明显长于Sham组(P＜0.01),而高压氧预处理能够逆转这种效应(P＜0.01).游泳速度四组之间无明显统计差异[F0.05(3,28)=2.23＜2.95,P＞0.05]. SPS暴露后海马神经元细胞数量和密度明显减少,给予高压氧预处理后,神经元形态明显好转,但仍不及对照组.结论:高压氧预处理可以减少海马神经元细胞凋亡从而改善SPS暴露后大鼠认知功能障碍.     

Effects of testosterone on spatial learning and memory in adult male rats

A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting 7 days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects.     

慢性复合应激对大鼠学习记忆功能及脑ERK表达活化的影响

目的：研究慢性复合应激对大鼠学习记忆的影响,以及大脑细胞外信号调节激酶（ERK）表达活化的变化,探讨慢性应激致学习记忆损害的分子机制。方法：采用低温暴露、足电击、白噪声、束缚、尾部悬吊、睡眠剥夺、水平震荡等刺激方式,建立慢性复合应激大鼠模型。Morris水迷宫实验观察应激对学习记忆的影响;放射免疫法检测血清皮质酮（CORT）含量;Western blot检测ERK的表达。结果：应激组大鼠水迷宫训练潜伏期较对照组延长,应激3周时有所恢复,但4周时大鼠的训练潜伏期再次显著延长（P〈0.05）。同时应激组大鼠血清CORT水平增高,海马、前额皮质P-ERK水平降低（P〈0.05）,两者在应激3周时均出现短时恢复,但4周时再次下调。结论：海马、前额皮质ERK蛋白磷酸化水平的改变可能参与了慢性复合应激损害学习记忆的分子机制。     

Effects of pulsed electromagnetic fields on learning and memory abilities of STZ-induced dementia rats

Introduction: Recent studies have shown that pulsed electromagnetic field (EMF) has therapeutic potential for dementia, but the associated neurobiological effects are unclear. This study aimed to determine the effects of pulsed EMF on Streptozotocin (STZ)-induced dementia rats.Methods: Forty Sprague-Dawley rats were randomly allocated to one of the four groups: (i) control, (ii) normal saline injection (sham group), (iii) STZ injection (STZ group) and (iv) STZ injection with pulsed EMF exposure (PEMF, 10 mT at 20 Hz) (STZ + MF group). Morris water maze was used to assess the learning and memory abilities. Insulin growth factors 1 and 2 (IGF-1 and IGF-2) gene expression were determined by quantitative PCR. Results: The results showed that the mean escape latency in STZ-induced dementia rats was reduced by 66% under the exposure of pulsed EMF. Compared with the STZ group, the swimming distance and the time for first crossing the platform decreased by 55 and 41.6% in STZ + MF group, respectively. Furthermore, the IGF-2 gene expression significantly increased compared to that of the STZ group. Conclusions: Our findings indicate that the pulsed EMF exposure can improve the ability of learning and memory in STZ-induced dementia rats and this effect may be related to the process of IGF signal transduction, suggesting a potential role for the pulsed EMF for the amelioration of cognition impairment.     

Roles of oxytocin in spatial learning and memory in the nucleus basalis of Meynert in rats

The present study was performed to explore the role of oxytocin (OT) in spatial learning and memory in the nucleus basalis of Meynert (NBM) of rats. The latency, distance and swimming path to find the platform were tested by Morris water maze and recorded by a video camera connected to a computer. Intra-NBM injections of 2 or 10 nmol of OT, but not 0.2 nmol of OT, induced significant increase on the latency of spatial learning. Rats receiving intra-NBM administrations of 2 or 10 nmol of OT showed a more random search pattern. There were no significant changes in the swimming speed in Morris water maze test after the injection of OT. Furthermore, the impaired effect of OT on the latency of spatial learning was blocked by intra-NBM injection of the selective OT antagonist Atosiban, indicating that the effect of OT was mediated by OT receptor in the NBM of rats. Moreover, there were no influences of OT or Atosiban on the retention performance in rats. The results suggest that OT plays an inhibitory role in spatial learning in the NBM; the effect is mediated by OT receptor.     

基于Morris 水迷宫探讨不同贮食行为鼠类的空间记忆

鼠类的贮食方式(分散或集中)与其空间记忆能力有关,但有关两者的定量关系尚缺少实验证据。朝鲜姬鼠(Apodemus peninsulae)分散或集中贮藏食物;社鼠(Niviventer confucianus)、黑线姬鼠(A. agrarius)、昆明小鼠(Mus musculus)仅集中贮藏食物。利用Morris 水迷宫对4 种鼠的空间记忆能力进行了评估,以探讨其空间记忆能力与食物贮藏方式间的联系。结果发现:在5 d 的定位航行实验中,4 种鼠找到隐藏平台的潜伏期均呈现出显著的下降趋势,其中朝鲜姬鼠潜伏期最短,黑线姬鼠与社鼠次之,昆明小鼠最长。在空间探索实验中,朝鲜姬鼠、黑线姬鼠和社鼠穿越平台的次数显著大于昆明小鼠;实验鼠在目标象限内的时间比和路程比为:朝鲜姬鼠> 黑线姬鼠> 社鼠>昆明小鼠,但差异不显著。结果表明具有分散贮藏行为的朝鲜姬鼠的空间记忆能力较仅具有集中贮藏行为的其它鼠种强,暗示鼠类的食物贮藏方式与其空间记忆能力有一定联系。     

Morris water maze: a versatile and pertinent tool for assessing spatial learning and memory

Since its development about 40 years ago (1981–2021), Morris water maze has turned into a very popular tool for assessing spatial learning and memory. Its many advantages have ensured its pertinence to date. These include its effectiveness in evaluating hippocampal-dependent learning and memory, exemption from motivational differences across diverse experimental manipulations, reliability in various cross-species studies, and adaptability to many experimental conditions with various test protocols. Nonetheless, throughout its establishment, several experimental and analysis loopholes have galvanized researchers to assess ways in which it could be improved and adapted to fill this gap. Therefore, in this review, we briefly summarize these developments since the early years of its establishment through to the most recent advancements in computerized analysis, offering more comprehensive analysis paradigms. In addition, we discuss the adaptability of the Morris water maze across different test versions and analysis paradigms, providing suggestions with regard to the best paradigms for particular experimental conditions. Hence, the proper selection of the experimental protocols, analysis paradigms, and consideration of the assay’s limitations should be carefully considered. Given that appropriate measures are taken, with various adaptations made, the Morris water maze will likely remain a relevant tool to assess the mechanisms of spatial learning and memory.     

磁场对小鼠两种迷宫学习记忆的影响

据发现,磁场对生物体有一定作用,但是磁场对于人类或实验动物的学习记忆是否有影响,目前的报道结果很不一致。本实验采用实验小白鼠,给予不同强度（65高斯／50Hz,35高斯/25Hz）的低频磁场照射（每天1小时,持续25天）。磁场照射后,采用旷场行为测试、Y-迷宫和Morris水迷宫,检测小鼠的活动性、空间辨别、空间学习记忆和非空间学习记忆能力。结果表明：65高斯／50Hz磁场显著增高小鼠的活动性,并损伤小鼠Y-迷宫的空间辨别能力,但对Morris水迷宫的空间、非空间学习记忆无明显影响。35高斯／25Hz磁场处理动物行为在三个指标上均接近对照组。提示：长期的磁场照射可能会给动物,甚至人类造成一些影响。     

绿茶多酚对脑缺血大鼠血脑屏障及学习记忆功能的影响

目的 研究绿茶多酚(Green tea polyphenols,GTPs)对脑缺血大鼠血脑屏障(Blood-brain barrier,BBB)及学习记忆功能的影响.方法 双侧颈总动脉结扎法制备脑缺血大鼠模型,大鼠随机分为假手术组、模型组和GTPs治疗组,每组8只,观察GTPs的保护作用.应用Morris水迷宫测试大鼠学习记忆能力,甲苯胺蓝染色法观察大鼠海马CA1区神经元形态变化,透射电镜观察BBB的变化以及海马CA1区神经元超微结构改变.结果模型组与假手术组相比BBB破坏,海马CA1区结构紊乱,学习记忆能力明显下降(P＜o.05),GTPs治疗组与模型组相比,缺血性脑损伤明显减轻,学习记忆能力明显改善(P＜0.05).结论 GTPs能够减轻缺血性脑损伤,从而发挥改善脑缺血SD大鼠学习记忆能力的作用.     

Postnatal dexamethasone and long term learning and memory functions in developing rats: Effect of postnatal age and gender

In this study, we investigated the effect of dexamethasone on the long-term learning and memory functions in developing rats. In Sprague-Dawley rat pups, we administered a daily dose of dexamethasone (0.5 mg/kg/day) for three consecutive days in three groups of animals: the "ultra-early" group received steroids on postnatal days (PND) 1-3; the "early" group received the drug on PNDs 8-10, and the "late" group received the drug on PNDs 28-30. The control group was not given any medication. All animals underwent structured CNS examinations beginning on PND 15, and continued through PND 20. The pups were tested for spatial learning and memory functions using the Morris Water Maze (MWM) on PNDs 31 through 35, 45 through 49, and 59 through 63. They were also tested for reward-based learning and memory functions using Radial Arm Maze (RAM) on PNDs 70 through 72. We analyzed the effect of dexamethasone, postnatal age, and sex on neurological milestones, and learning and memory functions. We found that neurological examination findings were similar in all groups, as were the results of the reward-based learning using RAM. However, in the MWM, the total distance of swimming and the total time to find the hidden platform showed considerable difference among the groups. Although these functions improved with postnatal age, the female pups in all three steroid groups, and the male pups in the late-steroid group lagged significantly in learning and memory functions compared to the controls, and such lags were transient. However, the interaction terms between dexamethasone, age, and sex were also significant in MWM test results. Steroids administered postnatally may have transient, retarding effect on learning and memory functions, and that animal age and sex may modify such effects. Such lags are not global, but specific to the types of memory tests used, implicating different neural circuitries in the pathogenesis of such abnormalities. Although transient, if such adverse effects occur at critical phases during brain maturation, the implications for poor, long-term outcomes may be more significant. The mechanisms underlying such changes need to be explored.