氢溴酸樟柳碱对大鼠空间学习记忆能力的影响

目的探讨氢溴酸樟柳碱对空间学习记忆能力的影响。方法将40只SD大鼠随机分为4组:阴性对照组、氢溴酸樟柳碱低、中、高剂量组。通过尾静脉注射给药,阴性对照组给予0.9%氯化钠注射液,氢溴酸樟柳碱低、中、高剂量组分别给予0.3mg、3mg、15mg·kg~(-1)氢溴酸樟柳碱注射液,连续给药14d。采用Morris水迷宫试验评价氢溴酸樟柳碱对大鼠空间学习记忆能力的影响,并定期监测动物体质量变化。结果各组大鼠体质量在整个给药期呈现相似的增长趋势,组间比较差异无统计学意义。与阴性对照组比较,氢溴酸樟柳碱中、高剂量组能显著增加第1天上午训练时的上台潜伏期和上台前路程(P 0.05,P 0.01);随着训练次数的增加,各剂量组大鼠在训练后期,潜伏期及路程均低于阴性对照组,其中高剂量组在第2天下午的潜伏期,中剂量组和高剂量组分别在第3天上午、第2天下午的上台前路程,与阴性对照组比较显著降低(P 0.05)。站台撤除后,氢溴酸樟柳碱各剂量组大鼠的站台穿越次数和站台周围路程与阴性对照组相比差异无统计学意义。结论氢溴酸樟柳碱中、高剂量能干扰大鼠短期空间学习记忆能力以及促进长期空间学习记忆能力,对大鼠的空间学习记忆具有双相作用。     

戊四氮对大鼠空间学习能力及情感行为的影响

目的 戊四氮(Pentylenetetrazole,PTZ)作为一种化学致癫剂往往用来在大鼠癫痫模型中检测某些潜在抗惊厥剂的抗癫效能,但目前关于戊四氮所模拟的癫痫发作后症状并未彻底研究.本研究旨在评估PTZ点燃大鼠的认知及情感功能损害的程度.方法 24只大鼠随机分为PTZ组(n=16)和对照组(n=8),PTZ组大鼠给予35mg·kg-1·48h-1,连续28天,对照组给予相应的生理盐水.停药一周后将造模成功大鼠进行学习能力和情感反应性的评估.结果 PTZ组大鼠在水迷宫测定中,寻找平台的潜伏期时间与对照组相比,没有显著差异,而对平台空间位置的记忆能力较对照组差(P＜0.01).在强迫游泳试验、系统性抓握试验(systematic handling test)及旷场探查试验中,PTZ组大鼠均出现异常的情绪反应,与对照组有显著性差异(P＜0.01).结论 用PTZ点燃模型研究癫痫大鼠学习记忆能力及情感行为发现,癫痫大鼠在水迷宫中学习记忆能力下降,并可引发或加重实验动物活动习性改变、警觉水平增高、惊恐行为、环境适应能力下降.因而,PTZ点燃大鼠能够为我们提供一个很好的模拟人类癫痫发作后功能损害的动物模型,为今后寻找治疗癫痫患者认知、情感损害的合适疗法提供了平台.     

白藜芦醇对戊四氮致痫大鼠脑脊液、血清S100B蛋白的影响

目的研究白藜芦醇（Res）对戊四氮致痫大鼠脑脊液、血清S100B蛋白的影响。方法采用戊四氮（PTZ）腹腔注射建立慢性癫痫模型,造模成功后予以Res（15mg／kg·d）灌胃干预10d;采用酶联免疫吸附法测定脑脊液、血清S100B蛋白含量,海马标本行Nissl染色。结果经28d连续给药,18只大鼠符合Racine点燃标准,Res干预组大鼠痫性发作潜伏期明显延长,且发作时间明显低于癫痫模型组、二甲基亚砜组（P〈0．05）。海马Nissl染色提示Res干预对大鼠海马CAl、CA3区神经元有保护作用（P〈0．05）,而对齿状回保护作用不明显（P〉0．05）。Res干预组大鼠脑脊液、血清S100B蛋白含量低于癫痫模型组、二甲基亚砜组（P〈0．05）。结论Res降低PTZ致痫大鼠脑脊液、血清SIOOB蛋白含量,或许减缓癫痫发作脑损伤发挥神经保护作用。     

白藜芦醇对戊四氮致痫大鼠脑脊液、血清S1OOB蛋白的影响

目的 研究白藜芦醇(Res)对戊四氮致痫大鼠脑脊液、血清S100B蛋白的影响.方法 采用戊四氮(PTZ)腹腔注射建立慢性癫痫模型,造模成功后予以Res(15 mg/kg·d)灌胃干预10 d;采用酶联免疫吸附法测定脑脊液、血清S100B蛋白含量,海马标本行Nissl染色.结果 经28 d连续给药,18只大鼠符合Racine点燃标准,Res干预组大鼠痫性发作潜伏期明显延长,且发作时间明显低于癫痫模型组、二甲基亚砜组(P＜0.05).海马Nissl染色提示Res干预对大鼠海马CA1、CA3区神经元有保护作用(P＜0.05),而对齿状回保护作用不明显(P＞0.05).Res干预组大鼠脑脊液、血清S100B蛋白含量低于癫痫模型组、二甲基亚砜组(P＜0.05).结论 Res降低PTZ致痫大鼠脑脊液、血清S100B蛋白含量,或许减缓癫痫发作脑损伤发挥神经保护作用.     

SB-271046对匹罗卡品致痫大鼠空间学习记忆的影响

目的观察5-羟色胺6受体拮抗剂SB-271046对匹罗卡品致痫大鼠空间学习记忆的作用效应。方法成年雄性SD大鼠分为两组:空白对照组(Vehicle组,n=10),氯化锂-匹罗卡品组(Lithium chloride-Pilocarpine,LiCl-PILO组,n=40)。首先根据注射LiCl-PILO后是否出现癫痫持续状态(Status Epilepticus,SE),出现SE者纳入实验,未出现SE和死亡者则剔除;然后再随机分为3组:模型组即侧脑室注射羟丙基-β-环糊精(Hydroxypropyl-β-cyclodextrine,HP-β-CD),4μl;药物组按不同剂量分为2组,即侧脑室注射N-[4-Methoxy-3-(4-methyl-1-piperazinyl)-phenyl]-5-chloro-3-methylbenzo-thiophene-2-yl-sulphonamide monohydrochloride(SB-271047)剂量为10μg,4μl和侧脑室注射SB-271046剂量为20μg,4μl。结果在Y迷宫自主交替行为实验中,模型组自主交替率显著下降(P0.01),药物组显著提高尤其是20μg剂量组(P0.05)。在Y迷宫新奇事物探索实验中,模型组的新臂时间比显著下降(P0.01),药物组有提高趋势(P0.05)。在Morris水迷宫定位航行实验中,模型组平均潜伏期延长显著延长(P0.01),药物组明显缩短尤其是20μg剂量组(P0.05)。在Morris水迷宫空间探索实验中,模型组平均潜伏期延长,穿越平台次数减少,原平台象限停留时间缩短(P0.05),药物组有改善趋势(P0.05)。结论 SB-271046可以改善癫痫大鼠的空间学习记忆,主要作用于记忆获得巩固阶段,20μg剂量作用明显。     

Let-7c-1对戊四氮致痫大鼠学习记忆功能的作用

目的研究let-7c-1对戊四氮(pentylenetetrazol,PTZ)致痫大鼠学习记忆功能的影响,探讨其可能机制。方法通过PTZ腹腔注射SD雄性大鼠建立慢性癫痫模型,随机分为癫痫组、干预对照组、let-7c-1激动剂组,各组12只,另设12只大鼠为正常组。28 d后,观察各组大鼠的行为学变化,let-7c-1基因表达及大鼠海马组织中Bcl-2、Caspase3蛋白的表达。结果与正常组相比,癫痫组大鼠逃避潜伏期延长、穿越平台次数减少、在目标象限的总路程缩短,差异有统计学意义(P0.05);癫痫组与干预对照组相比,逃避潜伏期、穿越平台次数、在目标象限的总路程无统计学差异(P0.05);与干预对照组相比,let-7c-1激动剂组逃避潜伏期明显延长,穿越平台次数减少、在目标象限的总路程缩短,差异有统计学意义(P0.05)。干预对照组与let-7c-1激动剂组let-7c-1基因相对表达量分别为(1.35±0.32)、(62.53±21.01)(F=50.97,P0.05)。癫痫组let-7c-1基因表达量高于正常组,差异有统计学意义(P0.05)。let-7c-1激动剂组let-7c-1基因表达量明显高于干预对照组、癫痫组及正常组,差异有统计学意义(P0.05)。与正常组相比,癫痫组的Bcl-2蛋白表达减少,Caspase3蛋白表达增加,差异有统计学意义(P0.05);癫痫组与干预对照组相比,Bcl-2蛋白及Caspase3蛋白的表达无统计学差异(P0.05)。与干预对照组相比,let-7c-1激动剂组Bcl-2蛋白表达明显减少,Caspase3蛋白表达明显增加,差异有统计学意义(P0.05)。结论 Let-7c-1可能通过减少海马组织Bcl-2蛋白及增加Caspase-3蛋白表达使PTZ致痫大鼠的学习记忆功能受损。     

γ-氨基丁酸对慢性脑缺血致血管性痴呆大鼠学习记忆能力的影响

目的观察γ-氨基丁酸（GABA）对慢性脑缺血致血管性痴呆（VD）大鼠学习记忆能力及海马CA1区神经元形态学的影响。方法将SD大鼠随机分为假手术组、模型组、GABA组,采用双侧颈总动脉永久性结扎法建立VD模型。GABA组术后腹腔注射GABA0.5g.kg-1.d-1,连续注射60d;用Morris水迷宫实验检测大鼠空间学习记忆能力;Nissl染色观察大鼠海马CA1区神经元形态学变化。结果 GABA能明显改善VD大鼠学习记忆能力,也能减轻海马CA1区神经元损伤。结论 GABA能改善慢性脑缺血致VD大鼠的学习记忆能力,减轻海马神经元损伤可能是其机制之一。     

轻度颅脑损伤中应激因素对大鼠学习记忆的影响

目的探讨应激因素(惊吓)对轻度脑损伤大鼠恢复期学习记忆的影响。方法将30只实验大鼠随即分为损伤组、惊吓组与正常对照组。对Hall[1]脑损伤装置进行改进,制造清醒状态下大鼠轻度脑损伤模型。伤前3d及伤后10d通过Morris水迷宫试验检测损伤组、惊吓组与对照组学习记忆能力的差异。结果损伤组、惊吓组学习记忆能力与对照组比较有统计学意义(P<0.05),损伤组与惊吓组之间比较无统计学意义(P>0.05)。结论在轻度颅脑损伤中应激因素对学习记忆改变有重要意义。     

癫痫持续状态和慢性癫痫对大鼠学习记忆和情感行为的影响

目的探讨急慢性癫痫发作对大鼠认知功能的影响。方法戊四氮(PTZ)诱导大鼠癫痫持续状态(SE)和慢性癫痫(CEP),用交替电刺激Y迷宫试验、Morris水迷宫试验、抬高迷宫试验和旷场试验检测大鼠学习记忆和情感行为变化。结果SE大鼠致痫后近期水迷宫逃避潜伏期延长(P<0.05),平台象限搜寻时间百分比降低(P<0.01),穿越平台区域次数减少(P<0.05)Y迷宫选择错误总数增多(P<0.05);抬高迷宫开放臂中逃避时间延长(P<0.05),进入次数增多(P<0.05);旷场活动的格子数、站立次数及粪便颗粒数均减少(P<0.05)。远期均恢复正常。CEP大鼠致痫后近期水迷宫部分时段逃避潜伏期延长(P<0.05),远期恢复正常,Y迷宫选择错误总数近期和远期均增多(P<0.05)抬高迷宫开放臂中逃避时间和进入次数及旷场活动格子数、站立次数和粪便颗粒数与对照组相比均无明显差别(P>0.05)。结论癫痫持续状态可导致大鼠短期学习记忆功能受损和情感行为异常慢性癫痫引起的学习记忆能力降低持续时间较长,对情感行为无明显影响。交替电刺激Y迷宫在检测癫痫大鼠学习记忆功能方面可能较Morris水迷宫更灵敏。     

戊四氮点燃癫痫大鼠空间学习记忆障碍及海马突触素表达减少的研究

目的:探讨戊四氮点燃癫痫对大鼠空间学习记忆的影响及可能的分子机制。方法:戊四氮(pentylenetet-razol,PTZ)点燃建立慢性癫痫(chronic epileptic,CEP)模型,Morris水迷宫进行行为学检测,western blot方法观察大鼠海马突触素(synaptophysin,P38)蛋白的表达变化。结果:水迷宫试验检测癫痫组大鼠空间学习记忆能力受损(P<0.05,P<0.01);western blot结果表明海马P38蛋白表达较对照组明显减少(P<0.05)。结论:戊四氮点燃癫痫大鼠伴有学习记忆功能减退,其海马P38蛋白的表达减少可能参与了空间学习记忆受损。     

Spatial learning deficits and emotional impairments in pentylenetetrazole-kindled rats

Pentylenetetrazole (PTZ) is a chemical kindling agent used to examine the efficacy of potential anticonvulsants in rats. However, the extent to which PTZ mimics postseizure symptoms of epilepsy has not been thoroughly examined. This study assessed whether PTZ-induced seizures produce cognitive and emotional deficits that mimic those observed in many epileptic patients. Rats were given 30mg/kg PTZ or vehicle (intraperitoneally) every other day for 28 days. Those rats exhibiting consistent seizure activity were tested for learning ability and emotional reactivity, beginning 1 week following a single challenge dose of PTZ. Rats given PTZ made more reference memory errors in a radial arm water maze task, and exhibited emotional abnormalities in the forced swim test, the systematic handling test, and the open-field exploratory maze. Histological analysis revealed neuronal loss in the CA1 area and increased mossy fiber sprouting in the dentate gyrus, similar to what is observed in human epilepsy. These results indicate that PTZ kindling provides a useful model of postseizure dysfunction, which can serve as a screen for potential treatments for those cognitive, emotional, and neuropathological deficits that resemble those symptoms observed in human epilepsy.     

Effect of reversible inactivation of the supramammillary nucleus on spatial learning and memory in rats

Memory includes processes such as acquisition, consolidation and retrieval. Reference memory (RM) and working memory (WM) are two kinds of memory that can be assessed in rodents using spatial tasks, especially using the Morris water maze. The Morris water maze is particularly sensitive to hippocampal lesions. The supramammillary nucleus (SuM) has strong links with the hippocampus and septum. The role of the SuM on spatial learning is controversial. In the present study, involvement of SuM in the different steps of spatial RM and WM was investigated in the Morris water maze using reversible inactivation of SuM with lidocaine. Lidocaine (0.5 microl, 4%) was injected into the SuM through a guide cannula implanted above the SuM. The rats were trained on RM and WM versions of the Morris water maze. SuM was inactivated before training or immediately after training or before the probe trial of retrieval tests. Reversible inactivation of the SuM impaired consolidation of RM, and of consolidation and retrieval of WM. Therefore, it seems that activity of SuM neurons plays a role in spatial RM and WM learning and memory in the rat.     

Applications of the Morris water maze in the study of learning and memory

The Morris water maze (MWM) was described 20 years ago as a device to investigate spatial learning and memory in laboratory rats. In the meanwhile, it has become one of the most frequently used laboratory tools in behavioral neuroscience. Many methodological variations of the MWM task have been and are being used by research groups in many different applications. However, researchers have become increasingly aware that MWM performance is influenced by factors such as apparatus or training procedure as well as by the characteristics of the experimental animals (sex, species/strain, age, nutritional state, exposure to stress or infection). Lesions in distinct brain regions like hippocampus, striatum, basal forebrain, cerebellum and cerebral cortex were shown to impair MWM performance, but disconnecting rather than destroying brain regions relevant for spatial learning may impair MWM performance as well. Spatial learning in general and MWM performance in particular appear to depend upon the coordinated action of different brain regions and neurotransmitter systems constituting a functionally integrated neural network. Finally, the MWM task has often been used in the validation of rodent models for neurocognitive disorders and the evaluation of possible neurocognitive treatments. Through its many applications, MWM testing gained a position at the very core of contemporary neuroscience research.     

戊四氮致痫大鼠学习记忆改变及海马CA_1和CA_3区神经颗粒素的表达变化

目的 探讨戊四氮慢性点燃癫痫对大鼠学习记忆能力的影响及海马CA_1、CA_3区神经颗粒素(neu-rogranin,Ng)的表达变化.方法 采用戊四氮(pentylenetetrazole,PTZ)腹腔注射慢性点燃癫痫(chronic epileptic,CEP)模型,用Morris水迷宫和Y迷宫对大鼠进行学习记忆能力检测,运用免疫组织化学方法测定大鼠海马CA_1、CA_3区Ng的表达变化.结果 与对照组比较,慢性癫痫发作组大鼠在水迷宫中的逃避潜伏期延长(P<0.01),穿越平台次数减少(P<0.01),在Y迷宫中的错误反应次数增多(P<0.05).在海马CA_1区Ng的免疫反应强度减弱(P<0.05),CA_3区两组比较差异无统计学意义.结论 戊四氮慢性点燃癫痫大鼠学习记忆能力受损,海马CA_1区Ng表达减少可能参与了这一过程.

Abstract：

Objective To explore the effect of Pentylenetetrazole (PTZ)-kindled epilepsy on rats' learning and memory and the expression of neurogranin(Ng) in hippocampal CA_1 and CA_3. Methods Use chronic model of epilepsy induced by PTZ intraperitoneal injection. The ability of learning and memory were assessed by the Morris water maze and Y maze. The expression of Ng in hippocampal CA_1 and CA_3 was determined by immunocytochemical method respectively. Resuits The learning and memory ability of the epilepsy rats was impaired. Meanwhile,The immunological reaction of Ng for CEP group at CA_1 was weaker than NC group, but it made no difference at CA_3. Conclusion The impairment of learning and memory ability of the epilepsy rats might be related with the changes of Ng in hippocampal CA_1.     

戊四氮点燃癫癎大鼠空间学习记忆改变及海马NR2B表达

目的观察戊四氮点燃癫癎大鼠空间学习记忆功能变化及海马NMDA2型受体(NR2)B亚单位(NR2B)表达,探讨二者的关系及PTZ致癎大鼠认知障碍发生的分子机制。方法采用戊四氮(PTZ)慢性癫癎(CE)模型,Y-迷宫对两组大鼠进行行为学检测,免疫组织化学方法观察两组大鼠海马CA3区NR2B表达的变化,反转录多聚酶链反应(RT-PCR)方法检测大鼠海马NR2B mRNA的表达。结果癫癎组大鼠空间学习记忆能力受损;其海马CA3区NR2B阳性细胞较对照组明显减少(P<0.01),同时伴有海马NR2B mRNA表达下降(P<0.01)。结论戊四氮点燃癫癎大鼠空间学习记忆受损可能与海马神经元NR2B的表达减少有关。     

Interleukin-1beta induces anorexia but not spatial learning and memory deficits in the rat

Sickness behaviors are a set of adaptive responses to infection that include lethargy, anorexia, and, of direct relevance to this work, learning and memory impairments. The proinflammatory cytokine, interleukin-1 beta (IL-1β) has been proposed as the primary peripheral mediator of these sickness behaviors, though few studies have investigated the effects of peripheral IL-1β on learning and memory. We used three different versions of the Morris water task (Morris water task), a spatial learning and memory task, to separately assess the effects of peripheral IL-1β on acquisition, consolidation, and retention of spatial location information. Using a dose that induced anorexia, assessed as a significant reduction in body weight, we observed no performance impairments in the IL-1β-treated rats across the different versions of the task, suggesting that peripheral IL-1β alone is insufficient to induce spatial learning and memory impairments in the rat. The observed dissociation of anorexia and cognitive dysfunction suggests that, either spatial learning and memory are not principal components of the sickness response, or cognitive dysfunction requires different or additional peripheral mediator(s).     

Effects of intrahippocampal injection of ghrelin on spatial memory in PTZ-induced seizures in male rats

Ghrelin (gh) is a peptide hormone that may affect learning and memory. There is some evidence that ghrelin can have antiepileptic effects. So we decided to investigate the possible effects of ghrelin on spatial memory following PTZ-induced seizures in male rats. Ninety male rats were divided into 9 groups including control, saline, ghrelin (0.3, 1.5 or 3 nmol) and pentylenetetrazol (PTZ, 50 mg/kg, i.p.) plus saline or ghrelin (0.3, 1.5 or 3 nmol). All groups were trained in Morris water maze (MWM) for two consecutive days. Our results showed that ghrelin significantly improves spatial memory at the doses of 1.5 or 3 nmol (P < 0.05) in normal rats. We also demonstrated the significant impairment of spatial memory in PTZ group (P < 0.05). Intrahippocampal injection of ghrelin at the dose of 3 nmol significantly improved spatial memory in PTZ + gh group compared to PTZ group (P < 0.05). These findings suggest that ghrelin as a neuropeptide can improve spatial memory in PTZ-treated rats.     

巴曲酶对大鼠颞叶梗塞后学习障碍的改善作用

目的研究巴曲酶对大鼠左侧颞叶梗塞后空间学习障碍的改善作用。方法采用立体定向光化学诱导脑梗塞技术选择性地导致大鼠左侧颞叶皮层梗塞,术前３０分钟及术后第３天分别给巴曲酶组大鼠腹腔注射巴曲酶８ＢＵ／ｋｇ,行为实验装置由Ｍｏｒｒｉｓ水迷宫及图像自动监视系统组成。结果（１）巴曲酶可以显著地缩短梗塞大鼠在Ｍｏｒｒｉｓ迷宫中搜索目标的平均反应时和行程;（２）巴曲酶组大鼠较多、较早地使用了正常的认知策略。结论巴曲酶对左侧颞叶梗塞大鼠空间认知功能障碍具有明显的改善作用。它除了溶栓作用外,还参与了神经损伤的修复过程。