高同型半胱氨酸血症对大鼠在Morris水迷宫实验中学习记忆行为的影响

目的 研究高同型半胱氨酸血症对大鼠在Morris水迷宫实验中学习记忆能力的影响.方法 以高蛋氨酸饮食喂养大鼠,制作高同型半胱氨酸血症模型.进行隐藏平台获得实验、空间探索实验,比较高同型半胱氨酸组与对照组的学习记忆能力.结果 Z隐藏平台获得实验第3d高同型半胱氨酸血症组大鼠逃避潜伏期长于对照组(P＜ 0.05);空间探索实验高同型半胱氨酸血症组目的象限停留时间比及游程比、穿过原平台位置的次数均低于对照组(P＜0.05).结论 高同型半胱氨酸血症可致大鼠空间学习记忆能力下降.     

影响小鼠Morris水迷宫成绩的因素探讨及改进措施

Morris水迷宫自英国心理学家Richard Morris于1981年首次使用以来,已成为一种研究与海马功能直接相关的空间学习记忆机制的标准模式,能较准确地反映动物的空间参考记忆能力[1].Morris水迷宫能为考察实验动物空间认知能力提供较多的评价指标,全面记录其认知加工过程,客观地反映其认知水平.但是,Morris水迷宫的实施过程中还有很多影响其准确性和可靠性的因素存在,如实验动物的选择、实验设计、实验的实施过程等.因此,笔者现就影响小鼠Morris水迷宫成绩的若干因素(Morris水迷宫自身因素及小鼠主观因素等)进行综述,以期为实验工作者们减少误差提供一些帮助.     

化学点燃癫痫大鼠在水迷宫中学习记忆能力与海马中bFGF表达的关系

目的 观察印防己毒(picrotoxin，PTX)化学点燃癫痫大鼠在水迷宫中学习记忆训练与大鼠海马中碱性成纤维细胞生长因子(basic fibroblast grouth factor，bFGF)表达变化的关系，为进一步研究癫瘸患者记忆损害及其治疗提供线索。方法 44只雄性SD大鼠随机分为点燃组和对照组，分别用PTX和生理盐水腹腔注射，根据点燃情况点燃组再分为全面发作(A)、频繁发作(B)及部分发作(C)3组和迷宫对照(D)组，后者再分为迷宫训练(E)组和对照组(F)。然后进行水迷宫行为测试评价其学习记忆能力。用免疫组化和原位杂交法测定各组大鼠海马中bFGF表达变化。结果 癫痫大鼠在水迷宫测定中，除B组第1天的成绩较对照组差外，其余各组及B组在第2、3、4、5天中寻找平台的潜伏期时间与对照组相比差异无显著性。点燃各组对平台空间位置记忆的能力较对照组要差，差异有显著性。大鼠海马中，bFGF免疫组化染色阳性细胞在点燃各组和E组表达增高，bFGFmRNA在点燃各组和E组表达增强，而以A、B、C组表达增高最明显。结论 首次用化学点燃模型研究癫瘸大鼠在水迷宫中的学习记忆能力，发现PTX化学点燃癫痫大鼠在水迷宫中学习记忆能力下降，发作频繁者学习记忆受损明显，与发作的严重程度无关。水迷宫训练可使化学点燃癫痫大鼠海马中bFGF表达增高，对记忆损害有保护作用。     

化学点燃癫痫大鼠在水迷宫中学习记忆能力的测定

目的 观察印防己毒（Picrotoxin,PTX)化学点燃癫痫大鼠在水迷宫中学习记忆能力与发作频率及类型的关系。为进一步研究癫痫患者记忆损害的治疗提供线索。方法 34只雄性SD大鼠随机分为点燃组和对照组。分别用PTX和生理盐水腹腔注射，根据点燃情况点燃组再分为全面发作（A），频繁发作（B）和部分发作（C）组，对照组即为迷宫训练（D）组。然后进行水迷宫行为测试，评价其学习记忆能力。结果 癫痫大鼠在水迷宫测定中，除B组第1天的成绩较对照组差外，其余各组及B组在第2，3，4、5天中寻找平台的潜伏期时间与对照组相比没有显著性差异。点燃各组对平台空间位置的记忆能力较对照组要差。差异有显著性。结论 首次用化学点燃模型研究癫痫大鼠在水迷宫中的学习记忆能力后发现。PTX化学点燃癫痫大鼠在水迷宫中学习记忆能力下降。发作频繁者学习记忆受损明显，但与发作的严重程度无关。     

九盒迷宫试验检测慢性失眠者记忆功能

目的 探讨慢性失眠对记忆的影响.方法 选取55例原发性失眠(PI)患者、119例抑郁伴发失眠(CDI)患者和50名健康对照者(对照组),采用九盒迷宫进行客观记忆(空间工作和空间参考记忆、物体工作和物体参考记忆)检测,按0(很差)～4(很好)5个等级让受试者自我评定记忆.结果 与对照组相比,PI患者轻度时记忆自评[四分位数间距,记忆自评单位为等级,其他指标均为错误数,3(2,3)与1(1,2)]和重度时空间工作记忆[3(1,5)与6(2.5,11)]差(×2=4.526、3.529,均P＜0.01).CDI患者轻度时记忆自评[2(1,2)]和空间工作记忆[6(3,10)]差(×2=5.803、4.155,均P＜0.01),重度时物体参考[0.5(0,1)]和空间参考记忆[1.5(1,3)]也变差(×2=2.641、3.955,均P＜0.01).结论 PI损害主观记忆,严重时损害空间工作记忆.CDI损害记忆范围更广,包括主观、物体参考、空间参考和空间工作记忆.     

Wistar Rat全脑反复缺血再灌流后免疫功能变化及其机理研究

本文采用HPLC技术、放免分析及免疫细胞体外培养技术观察了全脑反复缺血对大鼠神经内分泌及免疫功能的变化。结果表明,Wistar Rat脑反复缺血后15天,其免疫功能增强,表现为胸腺ConA反应性明显增高,血清FSH水平明显降低,血清TSH水平明显升高,下丘脑NE、DA及5—HT含量减少,提示全脑反复缺血使下丘脑单胺类递质代谢紊乱,性腺轴功能降低,甲状腺轴功能增高,而导致免疫功能表达增强,但对全脑反复缺血后机体免疫功能增强的详尽机理尚待进一步研究。     

Wistar鼠全脑反复缺血再灌流6脑区中精氨酸加压素含量…

精氨酸加压素（ＡＶＰ）是脑内重要的神经递质，本研究采用４血管关闭的方法，制造Ｗｉｓｔａｒ大鼠全脑反复缺血再灌流长期生存动物模型，然后利用放免方法测定了缺血后存活不同时间大鼠额叶，颞叶，海马，丘脑，纹状体，脑干６个脑区的ＡＶＰ含量。发现缺血即刻各脑区ＡＶＰ无显变化（Ｐ＞０．０５），缺血后１５天显著下降（Ｐ＜０．０１），３０天时继续下降（Ｐ＜０．０１），６０时变化方趋稳定，９０天和１８０天时和对照组比     

鼠脑反复缺血再灌注海马6种氨基酸、单胺递质及其代谢产物变化的研究

目的：研究脑反复缺血后海马细胞外液氨基酸和单胺递质及其代谢产物的变化规律。方法：采用Ｐｕｌｓｉｎｅｌｌｉ和Ｂｒｉｅｒｌｅｙ４血管闭塞的方法,使鼠脑反复缺血,海马微管透极与高压液相电化学检测,观察细胞外谷氨酸（Ｇｌｕ）,天门冬氨酸（Ａｓｐ）,谷氨酰胺,牛磺酸、丙氨酸,丝氨酸,多巴胺（ＤＡ）,５－羟色胺（５－ＨＴ）及其代谢产物浓度的变化。结果：缺血期,Ｇｌｕ和Ａｓｐ骤然增高５０倍和３０倍。缺血期ＤＡ和５－ＨＴ含量分别增加３０倍和５０倍,随后逐渐下降,再灌注１００ｍｉｎ恢复到基线水平,与此同时,其酸性代谢产物３,４－二羟苯乙酸（ＤＯＰＡＣ）,高香草酸（ＨＶＡ）,５－羟吲哚乙酸（５－ＨＩＡＡ）在缺血期明显下降。结论：缺血期海马细胞外液兴奋性氨基酸和单胺递质急剧大量释放并触发膜离子通道改变。Ｃａ＾＋超载,自由基反应,共同     

慢性脑缺血海马CA1区HCN1蛋白表达下调与学习记忆损伤研究

目的 探讨慢性脑缺血导致大鼠认知功能障碍与HCN1通道亚型蛋白表达变化的内在关系。方法 健康成年雄性SD大鼠20只,随机分为假手术组、缺血组,每组各10只。各组缺血4周后采用Morris水迷宫检测大鼠学习记忆功能,免疫组化检测HCN1表达水平,进一步用蛋白印迹检测HCN1蛋白表达水平。结果 与假手术组相比,缺血组大鼠逃避潜伏期明显延长(P<0.05); 缺血组大鼠海马CA1区HCN1蛋白表达水平明显降低,与模型组比较有明显差异(P<0.05)。结论 慢性脑缺血海马CA1区存在HCN1通道亚型表达下调且参与大鼠认知功能损伤,可能为治疗慢性脑缺血所致认知功能障碍的新靶点。     

大鼠脑缺血后诱发学习和记忆障碍模型的研究进展

此文介绍9种脑缺血造成记忆障碍大鼠痴呆模型。血管性痴呆是因脑血管疾病所致的智能及认知功能障碍的临床综合征。脑血管病变是血管性痴呆的基础，在大脑实质可见出血或缺血损害，以缺血性多见。根据血管性痴呆的病理特征此文选取了二血管闭塞法、三血管闭塞法、四血管闭塞法、舌下静脉注射铁粉建立血管性痴呆模型、多发梗死性痴呆动物模型、高血压脑卒中自发大鼠动物模型、高脂血症血管性痴呆大鼠模型、去大脑皮层血管性痴呆动物模型、大脑中动脉闭塞法模型计9种脑缺血模型。并通过对其行为学和形态学筛选，似可模拟血管性痴呆模型．其方法各有所长，适合不同实验方法。     

Evaluation of learning and memory dysfunction and histological findings in rats with chronic stage contusion and diffuse axonal injury

We previously reported a modified fluid percussion device capable of consistently producing experimental cortical contusion (CC) and diffuse axonal injury (DAI) in separate groups of rats by lateral and midline fluid percussion, respectively. The purpose of the present study was to compare the differences in learning acquisition and memory retention impairments between these two types of injured rats in the chronic stage using the Morris water maze technique. We also compared the histological differences between these two different types of traumatic brain injury. The results showed a statistically significant difference in learning acquisition impairment between the sham and CC rats and also between the sham and DAI rats. However, a significant difference in memory retention impairment was observed only between the sham and DAI rats. Histologically, the neuronal cell loss of CA3 pyramidal cells in the hippocampus was observed on the ipsilateral side in the CC and bilaterally in DAI. The neuronal cell loss was seen in bilateral entorhinal cortex layer II in DAI, but it was not seen in CC. From these results, we speculate that the marked cell loss in the hippocampus CA3 region in both CC and DAI rats was related to the impairment of spatial learning acquisition. The marked cell loss in entorhinal cortex layer II in DAI rats may be one of the important factors in the impairment of spatial memory retention.     

Ischemic tolerance to memory impairment associated with hippocampal neuronal damage after transient cerebral ischemia in rats

When rats were trained preoperatively with a three-panel runway task and were then exposed to 10-min ischemia by the method of 4-vessel occlusion, they showed no increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points), having normal retention of memory performance learned before the ischemic insult. Next, we investigated the abilities of ischemic rats to acquire the three-panel runway task and to learn a subsequent reversal task, where the correct panel-gate locations were changed. Rats with 5-min ischemia exhibited performance as good as that of control rats, but rats exposed to 10- and 20-min ischemia showed more errors than control rats during 10 acquisition sessions and 5 subsequent reversal sessions, each of which (consisting of 6 trials) was given once a day. Marked neuronal degeneration was observed in the hippocampal CA1 sector from the rats with 10- and 20-min ischemia. Exposure to sublethal 5-min ischemia followed by 10-min ischemia at a 2-h interval had no effect on either the memory impairment during acquisition and reversal tests or the hippocampal CA1 damage. When rats were exposed to 5-min ischemia 2 days before lethal 10-min ischemia, they showed acquisition and subsequent reversal learning as good as that of control rats. Preconditioning with sublethal 5-min ischemia followed by 2 days of reperfusion also prevented the neuronal destruction of the hippocampal CA1 sector induced by 10-min ischemia. These findings suggest that postischemic hippocampal CA1 neuronal damage does not affect retention of spatial memory acquired before ischemia, but produces a significant impairment of acquisition and subsequent reversal learning. The present results also demonstrate that preconditioning with sublethal ischemia can develop tolerance to subsequent lethal ischemia to prevent the learning impairment related to the hippocampal CA1 neuronal damage.     

脑缺血后脑室内注射胰岛素减轻大鼠学习记忆力损害的实验研究

目的探讨经脑室直接注射胰岛素对全脑缺血后大鼠学习记忆力的影响.方法以4-VO法建立大鼠全脑缺血再灌注模型.全脑缺血20min后行再灌注,于再灌注即刻经脑室注入1U胰岛素,缺血再灌注后8周利用三等分Y型迷宫箱测试大鼠的学习记忆功能,并对大鼠海马CA1区神经元的病理改变进行观察.结果经Y型迷宫测试,对照组、治疗组及缺血组大鼠达9/10正确反应所需电击数分别为5.6±1.2,8.6±1.3,19.6±2.6;对照组、治疗组及缺血组大鼠海马CA1区神经元计数分别为176.5±10.6,112.4±11.7,10.5±0.4.结论全脑缺血后脑室内注射胰岛素可明显减少大鼠海马CA1区神经元的死亡,进而减轻大鼠学习记忆力损害.     

Decreased expression and impaired function of muscarinic acetylcholine receptors in the rat hippocampus following transient forebrain ischemia

In this study, we investigated whether transient cerebral ischemia affects the function and molecular expression of specific muscarinic cholinergic receptors. Our results show that in contrast to the GABA-B and A1 adenosine receptor systems, the ability of muscarinic receptors to attenuate evoked excitatory responses at vulnerable CA1 synapses is significantly attenuated by 18 h following reperfusion. This attenuation in efficacy was restricted to the vulnerable CA1 subfield, as no significant change in muscarinic receptor-mediated attenuation of evoked responsiveness was observed within post-ischemic dentate granule cell synapses. Expression analysis revealed that the mRNA and immunoreactive protein levels for individual types of muscarinic receptors respond differently and uniquely to transient cerebral ischemia insult. Of particular interest is the m4 subtype of receptor, whose mRNA and protein expression levels were significantly diminished within the hippocampus by 12 and 24 h following reperfusion, respectively. As the m4 muscarinic receptor localizes to presynaptic terminals within the hippocampus, a decrease in its expression could account for the impaired functional responsiveness of the muscarinic receptor system following ischemic insult. Taken together, these results demonstrate that transient forebrain ischemia leads to dynamic alterations in the gene expression, protein prevalence, and functionality of muscarinic receptors in the post-ischemic hippocampus at times preceding the degeneration of the vulnerable neurons.     

c-Jun、bFGF、HSP70在丹参改善颞叶缺血大鼠空间记忆障碍中的表达变化

目的：探讨在丹参改善单侧颞叶缺血大鼠空间记忆障碍中c-Jun,bFGF和HSP70的表达变化。方法：采用立体定向光化学方法选择性地导致大鼠左侧颞叶皮层缺血,术前30分钟及术后第3天分别给丹参组大鼠腹腔注射丹参10g／kg,用Morris水迷宫及图像自动监视系统监测大鼠行为。然后取脑进行病理学及c-Jun、bFGF和HSP70免疫组化分析。结果：经丹参治疗,颞叶缺血性损害大鼠的空间记忆障碍得到显著改善,颞叶缺血损害程度显著减轻,缺血灶内c-Jun、bFGF和HSP70表达明显减少。结论：丹参可以明显改善单侧颞叶缺血性损害大鼠的空间记忆障碍,其机制可能与丹参减轻颞叶缺血损害,下调c－Jun、bFGF和HSP70表达有关。     

Baseline and 8-OH-DPAT-induced release of acetylcholine in the hippocampus of aged rats with different levels of cognitive dysfunction

During aging, neurotransmission systems such as the cholinergic and serotonergic ones are altered. Using rats aged 3 or 24-26 months, this study investigated whether the well-described 8-OH-DPAT-induced increase of hippocampal acetylcholine release was altered in aged rats and whether it may vary according to the magnitude of age-related cognitive deficits. Long-Evans female rats aged 24-26 months were classified as good or bad performers on the basis of their reference-memory performance in a Morris water-maze task. Subsequently, the efficiency of 5-HT(1A) receptor agonist 8-OH-DPAT (0.5 mg/kg, s.c.) in triggering hippocampal acetylcholine release was evaluated by in vivo microdialysis and high performance liquid chromatography analysis. Besides a reduced baseline release in aged rats and a correlation between the baseline release and probe-trial performance in all rats, the results demonstrated that 8-OH-DPAT produced a significant increase of hippocampal acetylcholine release (peak value) in all rats, whether aged or young. While significant in bad performers (+56%), this increase did not reach significance in good performers (+32%). The results suggest that (i) some aspects of cognitive alterations related to aging might be linked to the baseline release of acetylcholine in the hippocampus, and (ii) the cholinergic innervation of the hippocampus of aged rats responds almost normally to systemic activation of 5-HT(1A) receptors, and (iii) differential alterations of cholinergic/serotonergic interactions assessed by determination of the 8-OH-DPAT-induced release of acetylcholine in the hippocampus could not be linked with clarity to the cognitive status of aged rats.     

Effects of discrete kainic acid-induced hippocampal lesions on spatial and contextual learning and memory in rats

Substantial information is available concerning the influence of global hippocampal lesions on spatial learning and memory, however the contributions of discrete subregions within the hippocampus to these functions is less well understood. The present investigation utilized kainic acid to bilaterally lesion specific areas of the rat hippocampus. These animals were subsequently tested on a spatial orientation task using a circular water maze, and on an associative/contextual task using passive avoidance conditioning. The results indicate that both the dorsal CA1 and the ventral CA3 subregions play important roles in learning. Specifically, CA1 lesions produced a deficit in the acquisition of the water maze task and a significant memory impairment on the passive avoidance task. CA3 lesions also caused learning deficits in the acquisition of the water maze task, and produced even greater impairments in performance on the passive avoidance task. We conclude that CA1 and CA3 hippocampal subregions each play significant roles in the overall integration of information concerning spatial and associative learning.     

Egocentric spatial orientation in a water maze by rats subjected to transection of the fimbria-fornix and/or ablation of the prefrontal cortex

The acquisition of a water maze based task requiring egocentric spatial orientation in the absence of distal cues was studied in four groups of rats: animals in which the fimbria-fornix had been transected, rats that received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham-operated control group. Isolated lesions of both the anteromedial prefrontal cortex and the hippocampus were associated with a significantly impaired task acquisition. Both of these individually lesioned groups did, however, eventually demonstrate full functional recovery by reaching the task proficiency of the sham-operated control group. In contrast, the group in which both of these structures had been lesioned failed to demonstrate full functional recovery and was severely and long-lastingly impaired when compared to all other groups. Behavioural challenges in the form of a no-platform session and two reversals of platform position demonstrated that while the sham-operated control group and the group subjected to fimbria-fornix transections in isolation utilized rather pure egocentric orientation strategies, the two prefrontally lesioned groups (and especially the combined lesion group) employed a different set of solution strategies which at least partly relied on a "circling" method. Even in the behaviour of the prefrontally lesioned groups, however, indications of a certain level of cognitive representations of the platform positions were seen. It is concluded that both the prefrontal cortex and the hippocampus contribute to the mediation of egocentric spatial orientation. Furthermore, the hippocampus is a significant and potentially irreplaceable part of the neural substrate of functional recovery of the presently studied task after prefrontal lesions--while the prefrontal cortex may play a similar role with respect to hippocampal lesions.     

Effects of hyperthermia on the effectiveness of MK-801 treatment in the gerbil hippocampus following transient forebrain ischemia

The effects of dizocilipine maleate (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor/channel antagonist, were tested on the dysfunction of neurotransmitter and signal transduction systems and morphological damage 7 days after transient forebrain ischemia in gerbils. Neurotransmitter system (adenosine A1, muscarinic cholinergic receptor) and signal transduction system (inositol 1,4,5-trisphosphate receptor: IP3, protein kinase C: PKC, L-type calcium channels) binding sites were mapped by in vitro quantitative receptor autoradiography. All ligands used in the present study decreased significantly in the CA1 subfield 7 days after ischemia. In normothermic animals, pretreatment with MK-801 failed to protect against decreased receptor binding in the hippocampus 7 days after ischemia. Moreover, in a morphological study, pre- and posttreatment of MK-801 failed to show protective effects against ischemic neuronal damage. On the other hand, pretreatment of MK-801, without maintaining body temperature, prevented the neuronal death of CA1 subfield 7 days after ischemia. These results weaken the hypothesis that NMDA receptor/channel may play a pivotal role in the pathogenesis of neuronal damage after transient forebrain ischemia.     

Complementary activation of hippocampal-cortical subregions and immature neurons following chronic training in single and multiple context versions of the water maze

Neurobiological studies of memory typically involve single learning sessions that last minutes or days. In natural settings, however, animals are constantly learning. Here we investigated how several weeks of spatial water maze training influences subsequent activation of neocortical and hippocampal subregions, including adult-born neurons. Mice were either trained in a single context or in a variant of the task in which the spatial cues and platform location changed every 3 days, requiring constant new learning. On the final day, half of the mice in each training group were tested in a novel context and the other half were tested in their previous, familiar context. Two hours later mice were perfused to measure subregion-specific expression of the immediate-early gene zif268, a marker of neuronal activation. None of the training paradigms affected the magnitude of adult neurogenesis. However, different neuronal populations were activated depending on prior training history, final context novelty, or a combination of these 2 factors. The anterior cingulate cortex was more activated by novel context exposure, regardless of the type of prior training. The suprapyramidal blade of the dentate gyrus and region CA3 showed greater activation in mice trained in multiple contexts, primarily after exposure to a familiar context. In immature granule neurons, multiple context training enhanced activation regardless of final context novelty. CA1 showed no significant changes in zif268 expression across any training condition. In naïve control mice, training on the final day increased zif268 expression in CA3, CA1 and the anterior cingulate cortex, but not the dentate gyrus, relative to mice that remained in their cages (transport controls). Unexpectedly, immature granule cells showed a decrease in zif268 expression in naïve learners relative to transport controls. These findings suggest novel and complementary roles for hippocampal, neocortical, and immature neuronal populations in learning and memory.