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1丰富环境或嗅觉缺失对小鼠高级认知功能的影响2.一种对吗啡依赖的自由活动大鼠进行睡眠脑电记录并分析的方法
陈艳梅
学位类型博士
导师马原野
2010-11
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业神经生物学
关键词焦虑 抑郁 嗅球摘除 氟西汀 Cnga2转基因小鼠 慢波睡眠 记忆重现荡 场电位 海马尖波 纺锤波 慢波振荡
摘要在大多数研究丰富环境对行为调节的正向作用的实验中,丰富环境处理都是在动物经历了应激或其他有可能损伤大脑功能的处理之后或直接在患病个体上进行的。在本研究中,为了使丰富环境和慢性应激的发生更合乎现代社会可能发生的情况,我们的小鼠在每天接受6小时或0小时束缚应激的同时,还被分别饲养于丰富环境或标准环境中。经过2周或4周处理之后,检测这些小鼠的感觉门控抑制和空间识别学习记忆能力。实验结果如下:1)接受或不接受慢性束缚应激并且饲养于丰富环境中2周的小鼠感觉运动门控抑制能力强于标准环境饲养的小鼠。2)丰富环境处理4周对小鼠的感觉运动门控抑制没有影响,但4周处理后,束缚应激使得饲养于标准环境中的小鼠感觉门控抑制能力增强而对丰富环境饲养的小鼠没有影响。3)慢性束缚应激4周的小鼠空间识别学习记忆能力受损,但饲养与丰富环境中的应激小鼠空间识别能力不受影响。本研究结果表明,丰富环境2周能提高小鼠的感觉运动门控抑制,并且不受动物是否接受慢性束缚应激的影响,但丰富环境4周之后小鼠的感觉门控抑制与标准环境饲养的小鼠没有区别;慢性束缚应激后,小鼠的空间识别记忆能力受损,但丰富环境能够逆转这种由应激导致的空间记忆损伤。在利用CNGA2转基因嗅觉缺陷小鼠所做的一些研究工作中,结果发现:1)CNGA2转基因小鼠嗅觉能力受损。2)CNGA2转基因小鼠具有明显的焦虑和抑郁样行为。3)5-HT重吸收抑制剂氟西汀(fluoxetine)对CNGA2转基因小鼠的焦虑和抑郁样行为没有缓解作用。本研究表明,嗅觉缺陷会导致小鼠明显的焦虑和抑郁,但与嗅球摘除造成的抑郁不一样,嗅觉缺陷转基因小鼠的抑郁不能被氟西汀缓解,说明这种转基因小鼠产生抑郁行为的机制不同于嗅球摘除。 大鼠吗啡成瘾相关记忆在慢波睡眠中处理特征的研究的一些方法及进展。在本实验中,首先利用气味线索建立大鼠的吗啡条件化位置偏好,使大鼠把某一特定气味与吗啡联系起来,在实验过程中,每天记录大鼠的睡眠脑电,检测慢波睡眠中与记忆巩固有关的脑电活动,如皮层的慢波振荡,纺锤波以及海马尖波的出现频率及时间,判断大鼠在睡眠过程中的信息处理特征。在大鼠建立起气味条件化位置偏好后,在大鼠睡眠过程中给予吗啡相关或非相关气味线索,检测睡眠过程中外部嗅觉信号刺激能否引发脑内与该嗅觉信息相关的记忆信息的重现和巩固,从而深入了解吗啡相关的记忆信息在脑内的处理过程。
其他摘要In most studies regarding the improving or therapeutical effects induced by enriched environment (EE), EE was performed after the stress treatment or in patients with certain diseases. In the current study, the effects of chronic restraint stress (6 h/day) in mice living in an enriched environment or standard environment (SE) were tested. Mice were randomly divided into 4 groups: non-stressed or stressed mice housed in SE or EE conditions (SE, stress + SE, EE, stress + EE). Prepulse inhibition (PPI) of startle was tested after the 2 weeks or 4 weeks stress and/or EE treatment and 1 or 2 weeks withdrawal from the 4 weeks treatment. After the 4 weeks treatment, spatial recognition memory in Y-maze was also tested. The results showed that EE increased PPI in stressed and non-stressed mice after 2 weeks treatment. No effect of EE on PPI was found after the 4 weeks treatment. 4 weeks chronic restraint stress increased PPI in mice housed in standard but not EE conditions. Stressed mice showed deficits on the 1 h delay version of the Y-maze which could be prevented by living in an enriched environment. Our results indicated that living in an enriched environment reversed the impairing effects of chronic restraint stress on spatial recognition memory. However, EE did not change the effects of stress on PPI.We tested anxiety-like and depression-like behaviors in thansgenic Cnga2–/Y mice. Our results showed that like the olfactory-bulbectomized (OBX) rats, Cnga2–/Y thansgenic mice were anxiety and depressive. They spent less time in the center area of the open field, the time spent in the white box of the white/black box was less in Cnga2–/Y mice than widetype mice. Furthermore, Cnga2–/Y mice were more immobile in forced swim test. After chronic fluoxetine (18mg/kg) treatment, the depressive and anxiety-like behaviour were not ameliated in Cnga2–/Y mice. In conclusion, Cnga2–/Y mice were more anxiety and depressive compared with the widetype mice, but the depression-like behaviour could not be reversed by chronic SSRI treatment. The mechanism under the depression and anxiety-like behaviour in these mice need further studies. Newly encoded memory traces could be reactivated in the hippocampus during slow wave sleep (SWS), and this reactivation is critical for the redistribution and integration of newly encoded memories into the network of preexisting long-term memories. Secondly, the studies during my postgraduate perioid were reported. In this section, one method was introduced, which was a combination of the odor cue related morphine addiction model and a technique for sleep recording in freely moving rats. We trained rats in a conditioned place preference (CPP) paradigm to make the rats associate odor cues (rose or mint) with morphine. EEG was recorded for 3 hr after the training each day. Slow oscillation, spindle and sharp wave ripple events and there durations were analysized from the EEG datas. After the rats learned the association between odor and morphine, morphine related odor or other odors were gave during the sleep to test if morphine related odor would induce memory reactivation and prompt the memory.
语种中文
文献类型学位论文
条目标识符http://ir.kiz.ac.cn/handle/152453/7394
专题认知障碍病理学
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陈艳梅. 1丰富环境或嗅觉缺失对小鼠高级认知功能的影响2.一种对吗啡依赖的自由活动大鼠进行睡眠脑电记录并分析的方法[D]. 北京. 中国科学院研究生院,2010.
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