Glucosamine alleviates scopolamine induced spatial learning and memory deficits in rats

Introduction and objectiveBeneficial effects of glucosamine in spatial learning and memory impairment induced by scopolamine has been evaluated in rats by using Morris water maze.MethodsMale Wistar rats were randomly divided into control, scopolamine and scopolamine plus glucosamine groups. All injections were given in 5 consecutive days and 30 min after each injection, the rats were tested in the Morris water maze test. Escape latency and path length to reach the hidden platform were subjected to analysis of variance [ANOVA].ResultsThe rats treated with scopolamine showed increased escape latency and path length to reach the hidden platform compared to control group (P < 0.001). Both escape latency and traveled path length to reach the hidden platform in glucosamine treated animals (1 and 2 g/kg) were significantly lower (P < 0.05 to P < 0.001) than in the scopolamine group.ConclusionThe results of this study showed that the glucosamine can inhibit scopolamine-induced impairments of spatial learning and memory in rats. Glucosamine might offer a promise in either the prevention or the treatment of neurodegenerative diseases such as Alzheimer's disease.     

急、慢性高原缺氧对成年大鼠空间学习和记忆功能的影响

 目的： 探讨急性和慢性高原缺氧对成年大鼠空间学习和记忆功能的影响。方法： 研究分三部分。实验一：成年雄性SD大鼠分为平原组（A组）和急性高原缺氧组（B组）（n=15）,B组于低压舱模拟海拔7 000 m高原连续暴露72 h后返回平原,24 h后两组同时进行Morris水迷宫定位巡航实验,连续训练3 d,每天4次,记录大鼠寻找平台的时间,第4天撤除平台,进行空间探索实验并记录大鼠穿越平台的次数和在目标象限停留的时间。实验二：成年雄性SD大鼠分为平原组（C组）和慢性高原缺氧组（D组）（n=13）,D组置于低压舱模拟海拔6 000 m高原连续暴露35 d后返回平原,24 h后两组同时进行Morris水迷宫定位巡航实验,连续训练5 d,每天4次,第6天进行空间探索实验。实验三：成年雄性SD大鼠先进行Morris水迷宫定位巡航实验和空间探索实验(方法同实验二）,于空间探索实验后随机分为平原组（E组）和急性高原缺氧组（F组）（n=15）,F组于低压舱模拟海拔7 000 m高原连续暴露72 h后返回平原,2 h后两组再同时进行空间探索实验。结果： B组缺氧暴露后第1天寻找平台的时间较A组显著缩短（P<0.05）,B组穿越平台次数和在目标象限停留时间百分比与A组比较差异无统计学意义。D组寻找平台潜伏期时间、穿越平台次数及在目标象限停留时间的百分比与C组相比,差异均无统计学意义。F组与E组缺氧前的各项指标均无显著差异,缺氧暴露后,F组穿越平台次数和在目标象限停留时间的百分比与E组相比差异无统计学意义。结论： 在本实验观察期内,急、慢性模拟高原缺氧对成年雄性大鼠对空间位置觉和方向觉（空间定位）的学习和记忆能力无显著影响（P>0.05）。急、慢性高原缺氧对工作记忆和空间参考记忆等功能的影响有待进一步研究。     

Ganglioside GQ1b improves spatial learning and memory of rats as measured by the Y-maze and the Morris water maze tests

Gangliosides are major components of cell membranes and are particularly enriched in the mammalian brain where they represent the major lipid constituents of the neuronal cell surface. In the central nervous system, gangliosides have a close connection to many neurophysiological functions related to neurogenesis, proliferation, synaptogenesis, and synaptic transmission. The previously reported effect of the tetra-sialoganglioside GQ1b in hippocampal CA1 neurons of brain slices showed that GQ1b enhanced ATP-induced long-term potentiation (LTP). However, there has been no clear evidence of the effects of GQ1b on learning and memory as measured using behavioral test. In the present study, we performed the Y-maze and the Morris water maze (MWM) tests to reveal the effects of GQ1b on spatial learning and memory following intracerebroventricular (ICV) injection of GQ1b. GQ1b-treated rats showed highly increased performance on the Y-maze and the MWM tests without any significant alteration of basal locomotor activity. Therefore, our behavioral data strongly suggest that GQ1b improves spatial learning and memory in rats. Also, these data support the previous finding that GQ1b treatment in hippocampal CA1 neurons of rodent brain slices increased ATP-induced LTP.     

丙泊酚对大鼠空间关联记忆能力影响的水迷宫行为测试研究

目的研究注射临床低剂量和高剂量的丙泊酚对大鼠空间关联记忆能力的影响。方法将30只大鼠随机分成3组：对照组、临床低剂量0．1mg／（kg·min）组和临床高剂量0．5mg／（kg·min）组。在注射丙泊酚1d后进行水迷宫实验,包括4d的定位航行和1d的空间探索实验。在定位航行实验中分别对3组大鼠进行I、Ⅱ和Ⅲ象限入水的训练,并记录3组大鼠的逃避潜伏期、游泳路程和游泳速度。在空间探索实验中将大鼠从未训练的Ⅳ象限入水,分别记录平台象限游泳时间、第一环点数以及总得分。结果在第1,2天的定位航行实验中,低剂量组与对照组大鼠的逃避潜伏期没有统计学差异（p〉0．05）;高剂量组逃避潜伏期比对照组显著延长（P〈O．05）。第3,4天的定位航行实验中,3组大鼠之间均未见差异（p〉0．05）。在空间探索实验中,从未训练的Ⅳ象限入水时,对照组、低剂量组和高剂量组大鼠的总得分分别为（2509．36±190．72）、（2378．55±210．69）和（1954．85±174．20）。低剂量组和对照组没有显著性差异（P〉0．05）;高剂量组与对照组存在显著性差异（P〈O．05）,即高剂量组比对照组总得分低。结论注射低剂量的丙泊酚不影响大鼠的空间关联记忆和空间记忆能力;高剂量丙泊酚在注射后前2d内降低大鼠的空间记忆能力,但2d后对大鼠的空间记忆能力没有影响,说明高剂量的丙泊酚降低了大鼠的空间关联记忆能力。     

应用水迷宫测试糖尿病大鼠空间记忆能力变化的研究

目的 研究大鼠患糖尿病后,空间记忆能力和空间关联记忆能力受到的影响.方法 将70只SD大鼠（体质量180 g±20 g）随机分成3组,对照组、1型糖尿病组和2型糖尿病组.采用STZ一次性腹腔注射和联合高脂饲料喂养的方法分别制备1型和2型糖尿病大鼠模型,检测血糖水平.在造模成功的1个月和3个月后,分别进行水迷宫实验,包括4 d的定位航行和1 d的空间探索实验.结果 在糖尿病造模成功的1个月后,大鼠没有发生明显的空间记忆能力或空间关联记忆能力障碍.造模3个月后,在定位航行实验中,2组糖尿病大鼠的逃避潜伏期都比对照组时间长,具有统计学差异（P＜0.05）.实验第2天开始,对照组逃避潜伏期的下降趋势明显,而糖尿病组下降缓慢.1型和2型糖尿病组之间的逃避潜伏期没有显著差异（P＞0.05）.造模3个月后,在空间探索实验中,从训练过的Ⅰ象限入水时,2个糖尿病模型组平台象限游泳时间短,第1环点数和总得分等参数低,与对照组的差异都具有显著意义（P＜0.05）,2型糖尿病组的参数值比1型糖尿病组稍低.从未训练的Ⅳ象限入水时,糖尿病模型组的参数值也均低于正常对照组,具有统计学差异（P＜0.05）,且1型糖尿病组的总得分比2型糖尿病组更低一些.结论 1型或2型的糖尿病大鼠会发生空间记忆能力和空间关联记忆能力的下降.本实验中2型糖尿病组的空间记忆能力比1型糖尿病组受到了更明显的影响,而1型糖尿病组的空间关联记忆能力受到的影响比2型糖尿病组更大.     

KA诱发癫痫反复发作损伤大鼠空间学习记忆及中脑多巴胺能神经元

目的探讨颞叶癫痫反复发作(Spontaneous recurrent se izure,SRS)对大鼠空间学习记忆影响及中脑内多巴胺能神经元变化。方法以红藻氨酸(kain ic ac id,KA)制备颞叶癫痫大鼠模型,以是否出现SRS为标准将KA大鼠分为伴有反复发作和不伴有反复发作组,盐水为对照组。分别进行水迷宫行为测试,评价其学习记忆能力;并用酪氨酸羟化酶(Tyrosine hydroxylase,TH)免疫组化方法来观察各组大鼠中脑内多巴胺能神经元变化。结果KA处理后,按照Rac ine描述标准,KA组动物发作全部达到4~5级。KA后3周大鼠19只出现SRS,16只未见SRS;Morris水迷宫发现,在5 d的空间学习记忆测试中,反复发作KA大鼠的寻找潜伏期明显长于不伴有SRS的KA大鼠和盐水对照组(P<0.01),而不伴有SRS组与盐水对照组没有明显差别;伴有SRS的KA组大鼠总共穿过平台次数显著少于不伴有SRS的KA组大鼠和盐水对照组(P<0.01)。TH免疫组织化学结果发现与不伴有SRS的KA大鼠和盐水对照组比较,伴有SRS的KA大鼠在腹侧被盖的多巴胺能神经元大量脱失(P<0.01)。结论KA大鼠癫痫反复发作可能与空间学习记忆障碍和在腹侧被盖多巴胺能神经元大量脱失相关。     

雌激素对阿尔茨海默病去势雌性SD大鼠学习记忆能力的影响

目的观察雌激素对阿尔茨海默病(AD)大鼠学习记忆能力的影响。方法首先采用Aβ1～40,1μL(10μg/μL)立体定位SD大鼠单侧海马内注射建立AD动物模型,二周后双侧卵巢切除术(OVX)制备去卵巢大鼠模型后给予雌激素替代治疗(ERT),最后通过Morris水迷宫观察动物模型的学习、记忆能力变化情况。结果 ERT组AD动物模型的水迷宫逃避潜伏期和目标象限游泳时间比OVX组明显缩短(P0.05)。结论雌激素具有改善AD大鼠模型认知功能的作用。     

Effects of pre-training morphine on spatial memory acquisition and retrieval in mice

The opioid system plays an important role in memory processess. Morphine mimics endogenous opioids by acting on opioid receptor in brain to regulate memory. However, the effects of morphine on spatial memory acquisition are controversial. Also, little evidence has suggested that morphine could affect the retrieval of spatial memory. In the current study, effects of pre-training morphine and naloxone on the acquisition vs. retrieval of spatial reference vs. working memory were examined using discrete water maze tasks in C57BL/6 mice. Pre-training morphine administration (7.5 and 15 mg/kg, i.p.) impaired the acquisition of both spatial reference memory and working memory. Motivation to escape from the water maze was not affected by morphine. Pre-test morphine also inhibited the retrieval of spatial working memory but not reference memory. The effects of morphine on the acquisition and retrieval of spatial working memory were eliminated by naloxone pretreatment (1 mg/kg). These results indicate that morphine could differentially modulate a variety of aspects of spatial memory and these effects are mediated by the mu-opioid receptor.     

雌激素对阿尔茨海默病模型大鼠学习记忆的影响

目的:探讨雌激素对阿尔茨海默病(Alzheimer’s disease,AD)模型大鼠学习记忆能力的影响。方法:选取雌性SD大鼠24只,随机分为假手术组、卵巢切除组(ovariectomy,OVX)、OVX+苯甲酸雌二醇组(estradiolbenzoate,EB),每组8只。于海马注射Aβ1-42建立AD大鼠模型,通过Morris水迷宫观察大鼠的学习记忆能力,同时用ELISA检测脑组织超氧化物歧化酶(super oxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、乙酰胆碱酯酶(acetylcholine esterase,ACh E)的活性,用免疫组化分析神经元型一氧化氮合酶(n NOS)并测定其OD值。结果:与OVX组比较,OVX+EB组逃避潜伏期明显缩短(P0.05),原平台象限活动时间明显增加(P0.05),穿越原平台次数明显增多(P0.05)。雌激素作用还提高大鼠脑组织SOD、ACh E和n NOS活性,降低MDA活性(P0.05)。结论:研究表明雌激素可改善AD模型大鼠的学习记忆能力,其机制可能通过提高脑组织SOD、ACh E和n NOS活性,降低MDA活性有关。     

异丙酚和七氟醚麻醉对新生鼠空间学习和记忆能力的影响

目的探讨异丙酚和七氟醚麻醉对新生鼠空间学习和记忆能力的影响。方法新生7 d龄SD大鼠,每90min给予30 mg/kg异丙酚或七氟醚吸入麻醉6 h,给予葡萄糖溶液组给予对照,于第7周进行Morris水迷宫实验测试空间学习和记忆能力的影响。结果异丙酚麻醉组2～4 d大鼠的潜伏期,游泳距离均明显长于对照组,表明异丙酚麻醉组有着明显的行为缺陷,而七氟醚吸入麻醉组和对照组相比没有明显的差异。结论异丙酚麻醉会引起新生鼠长久的学习和记忆能力的损伤,而七氟醚则没有此影响。     

Intracranial self-stimulation facilitates a spatial learning and memory task in the Morris water maze

Learning and memory improvement by post-training intracranial self-stimulation has been observed mostly in implicit tasks, such as active avoidance, which are acquired with multiple trials and originate rigid behavioral responses, in rats. Here we wanted to know whether post-training self-stimulation is also able to facilitate a spatial task which requires a flexible behavioral response in the Morris water maze. Three experiments were run with Wistar rats. In each of them subjects were given at least five acquisition sessions, one daily, consisting of 2-min trials. Starting from a random variable position, rats had to swim in a pool until they located a hidden platform with a cue located on its opposite site. Each daily session was followed by an immediate treatment of intracranial self-stimulation. Control subjects did not receive the self-stimulation treatment but were instead placed in the self-stimulation box for 45 min after each training session. In the three successive experiments, independent groups of rats were given five, three and one trial per session, respectively. Temporal latencies and trajectories to locate the platform were measured for each subject. Three days after the last acquisition session, the animals were placed again in the pool for 60 s but without the platform and the time spent in each quadrant and the swim trajectories were registered for each subject. A strong and consistent improvement of performance was observed in the self-stimulated rats when they were given only one trial per session, i.e. when learning was more difficult. These findings agree with our previous data showing the capacity of post-training self-stimulation to improve memory especially in rats with little training or low conditioning levels, and clearly prove that post-training self-stimulation can also improve spatial learning and memory.     

Nicotine improves AF64A-induced spatial memory deficits in Morris water maze in rats

Ethylcholine mustard aziridinium ion (AF64A) is a neurotoxic derivative of choline that produces not only long-term presynaptic cholinergic deficits, but also various memory deficits in rats similar to some characteristics observed in Alzheimer's disease patients. This study investigated whether nicotine (NCT) administration attenuated spatial learning deficits induced by intracerebroventricular AF64A treatment. AF64A (6 nmol/6 μl)-or saline (SAL)-treated rats were trained in Morris water maze task. NCT (0.025–0.25 mg/kg) was subcutaneously injected 5 min before the training every day. The results showed that moderate dose (0.10 mg/kg) of NCT attenuated AF64A-induced prolongation of escape latency. Furthermore, NCT dose-dependently recovered the AF64A-induced decrease of time spent in the target quadrant in the probe test. These results suggest that NCT improves AF64A-induced spatial memory deficits, and thus it is a potential therapeutic agent for the treatment of memory deficits in dementia.     

Hippocampal serotonergic damage induced by MDMA (ecstasy): effects on spatial learning

3,4-Methylenedioxymethamphetamine (MDMA) use has been associated with a decline in various aspects of mnemonic function in humans. We therefore postulated that MDMA-induced damage of serotonergic nerve terminals would alter hippocampal processing. Seven days following treatment with MDMA (2 x 20 mg/kg sc, given 12 h apart), rat spatial learning and memory were tested utilizing the Morris water maze (MWM). No statistical differences were found in MWM platform acquisition latency or pathlength between controls and MDMA-treated animals. Probe trials revealed significantly higher proximity score averages and significantly reduced preference for the target quadrant in the MDMA-treated animals. MDMA treatment resulted in significant reduction (34%) in hippocampal serotonin (5-HT) levels 14 days after initial treatment. The findings of this study demonstrate that hippocampal serotonergic lesions induced by MDMA may be ostensibly linked to a reference memory deficit in rats tested with the MWM.     

Hippocampal heterogeneity in spatial memory revealed by cytochrome oxidase

The oxidative metabolism was assessed in the septal, intermediate and temporal hippocampus in Wistar rats that were trained following a working memory schedule in the Morris water maze. The cytochrome oxidase histochemistry was measured at 90 min, 6, 24 and 48 h post-training. We found an increase in the septal dentate gyrus at 90 min, at 6 h the increase was also found in CA3 and CA1 regions and returned to basal levels at 24 h. In contrast, the intermediate region showed lower increase, limited to the dentate gyrus and CA3 at 24 h post-training. No changes were found in the temporal hippocampus. These findings suggest that septal and intermediate hippocampal zones participate in this spatial learning and contribute at different moments to process this information.     

Ontogenetic differences in retention of spatial learning tested with Morris water maze

Two experiments examined retention of spatial learning in rats using a Morris water maze. Retention was scored in terms of probe trial performance when the platform was removed. Latency to reach the platform location, percent of time in the quadrant that had contained the platform, and relative frequency of visits to the platform location were analyzed. Results of the first experiment showed that preweanlings and juveniles exhibited substantial forgetting at 3- and 7-day retention intervals. Forgetting in adults was much lower than that found in the younger animals, and no differences in amount of forgetting appeared between the 3- and 7-day retention intervals at any age. The second experiment showed that forgetting in juveniles was alleviated by a single training trial administered just prior to the probe trial. These results are discussed in terms of ontogenetic differences in memory processing and measurement issues pertinent to the Morris water maze test procedure. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 30: 329–341, 1997     

Preservation of accurate spatial memory in aged rats

Male rats were tested in an 8 arm radial maze from 6–26 months of age with 5 hr delay imposed between choices 4 and 5. At 26 months their spatial memory was more accurate than when they were first tested at 6 months and also more accurate than that exhibited by another 5 month old group tested concurrently. However, these old rats acquired a noval spatial habit more slowly than the younger animals. In a subsequent study, we compared the acquisition of accurate spatial memory by rats that were 3 or 21.5 months old at the start of training. Older rats adapted to the maze more slowly and required more sessions to achieve criterion with no delay imposed during the test. There was no reliable difference in acquisition when a 1 hr delay was imposed between choices 4 and 5, but the old rats learned more slowly with a 5 hr delay. On memory tests after criterion performance had been achieved, the older rats performed as well as the younger animals at all delay intervals. Aged rats are deficient in acquiring the skills required for accurate spatial memory, but once acquired these skills do not deteriorate. The possibility that other “memory” deficits associated with aging might be alleviated by overtraining is discussed.     

宫内缺氧对新生小鼠额叶皮质神经元内nNOS表达及对成年小鼠学习记忆能力的影响

为探讨孕鼠宫内缺氧对新生小鼠发育时期额叶皮质神经元内nNOS表达及对成年小鼠学习记忆能力的影响,本研究采用Tapanainen建立的缺氧模型致胎龄13、15、17d小鼠宫内缺氧,然后采用Nissl染色观察新生鼠发育时期P1、P7、P14、P28、P90额叶皮质内神经元的数量和形态变化;免疫组织化学染色方法观察新生鼠发育时期P1、P7、P14、P28、P90脑组织内nNOS阳性神经元的表达;Morris水迷宫实验检测P90小鼠的学习和记忆能力。结果显示:与正常组比较,宫内缺氧组小鼠额叶皮质神经元数量明显减少,额叶皮质神经元内nNOS的表达明显减弱。宫内缺氧组小鼠逃避潜伏期延长及穿环次数明显减少。以上结果提示宫内缺氧可导致新生鼠额叶皮质神经元数量明显减少及nNOS的表达也明显减弱,并引起成年小鼠学习记忆能力降低。     

孕酮抗氧化作用对去卵巢小鼠学习记忆能力的影响

目的观察孕酮与小鼠学习记忆功能的维持和改善是否存在相关性,并探讨其机制。方法60只雌性昆明小鼠随机分为5组,除SHAM组外,其余各组小鼠行双侧卵巢切除术。术后对各组小鼠分别腹腔注射不同剂量孕酮或生理盐水。Morris水迷宫测试训练检测各组小鼠学习记忆能力,随后取脑,检测海马组织的SOD、MDA含量及T-AOC。结果OVX组在若干个测试训练时段其空间学习记忆能力显著较差,而孕酮各剂量组表现较好。海马组织SOD含量:SHAM组和孕酮各计量组均显著较高(P<0.05);MDA含量:SHAM组和HP组显著较低(P<0.05);T-AOC:SHAM组和HP组显著增高(P<0.05)。结论雌、孕激素的缺乏会引起成年雌性小鼠学习记忆能力下降,孕酮的长期补充治疗可以通过组织抗氧化作用,抵抗脂质过氧化反应,提高组织的抗氧化能力,来缓解或改善小鼠学习记忆功能障碍。     

吗啡成瘾小鼠对正常小鼠学习记忆力能力的影响

目的:用BALB/C小鼠建立动物模型,观察吗啡成瘾戒断小鼠对其周围的正常小鼠学习记忆能力的影响。方法:将吗啡成瘾戒断小鼠与正常小鼠同笼饲养,然后用Morris水迷宫实验测定正常小鼠的学习记忆能力,应用RT-PCR的方法检测正常小鼠海马中PKCa、GABA分子表达的变化。结果:水迷宫实验证明,与生理盐水组相比,实验组小鼠的学习记忆能力明显降低(P<0.05),海马中PKCa和DABA的表达都明显升高(P<0.05)。     

苯丙胺对大鼠行为、学习能力及海马CA3区突触素表达的影响

目的观察苯丙胺对大鼠行为、空间辨别性学习能力和海马CA3区突触素表达的影响。方法将45只健康雄性SD大鼠随机分为:正常对照组、生理盐水组和苯丙胺组。①苯丙胺组每天肌注0.5mg/kg苯丙胺1次;②生理盐水组即注射等体积生理盐水;③正常对照组不予任何处理。每组大鼠分14d、28d和42d三个时间段进行一般行为学、学习记忆能力及海马CA3区突触素表达的检测。结果①苯丙胺组大鼠在注射苯丙胺10d后出现直立、点头、狂躁等行为改变。正常对照组、生理盐水组均无此现象出现;②苯丙胺组大鼠空间辨别性学习记忆能力的影响,在第1、2个时间段与对照组的比未见组间差异,在第3时间段的平均运行时间和正确率比对照组的延长和降低(P<0.05)。③苯丙胺组大鼠海马CA3区突触素表达在第一阶段比对照组的减少,并随着用药时间的延长减少的更明显(P<0.05)。结论苯丙胺对空间辨别性学习记忆时大鼠行为及海马CA3区突触素表达有影响。