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缺乏细胞周期蛋白 D2 会损害成年大脑神经发生,从而改变海马依赖的行为任务,而不会降低学习能力。

Lack of cyclin D2 impairing adult brain neurogenesis alters hippocampal-dependent behavioral tasks without reducing learning ability.

机构信息

Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.

出版信息

Behav Brain Res. 2012 Feb 1;227(1):159-66. doi: 10.1016/j.bbr.2011.11.007. Epub 2011 Nov 15.

Abstract

The exact function of the adult brain neurogenesis remains elusive, although it has been suggested to play a role in learning and memory processes. In our studies, we employed cyclin D2 gene knockout (cD2 KO) mice showing impaired neurogenesis as well as decreased hippocampal size. However, irrespectively of the genetic background of cD2 KO mice, this phenotype resulted in neither deficits in the hippocampal-dependent learning ability nor the memory formation. In the present study, cD2 KO mice and control littermates were subjected to hippocampal-dependent behavioral tests with little or no learning component. The knockout mice showed significant impairment in such species-typical behaviors as nest construction, digging, and marble burying. They were building none or poorer nests, digging less robustly, and burying fewer marbles than control mice. Such impairments were previously described, e.g., in animals with hippocampal lesions. Moreover, cD2 KO animals were also more active in the open field and automated motility chamber as well as showed increased explorative behavior in IntelliCage. Both increased motility and explorative behaviors were previously observed in hippocampally lesioned animals. Finally, cD2 KO mice showed normal sucrose preference, however starting from the second exposure to the sweetened solution, while control animals displayed a strong preference immediately. Presented results suggest that either morphological abnormalities of the hippocampal formation or adult brain neurogenesis impairment (or both) alter hippocampal-dependent behaviors of mutant mice without influencing learning abilities. These results may also suggest that adult brain neurogenesis is involved in species-typical behaviors.

摘要

成人脑神经发生的确切功能仍然难以捉摸,尽管有人认为它在学习和记忆过程中发挥作用。在我们的研究中,我们使用了 cyclin D2 基因敲除 (cD2 KO) 小鼠,这些小鼠表现出神经发生受损和海马体缩小。然而,无论 cD2 KO 小鼠的遗传背景如何,这种表型都不会导致海马体依赖性学习能力或记忆形成的缺陷。在本研究中,cD2 KO 小鼠和对照同窝仔鼠被置于海马体依赖性行为测试中,这些测试几乎没有或没有学习成分。敲除小鼠在筑巢、挖掘和埋大理石等物种典型行为中表现出明显的障碍。它们筑巢的能力很差或根本不筑巢,挖掘的力度也较小,埋大理石的数量也比对照小鼠少。这种损伤以前在海马体损伤的动物中已有描述。此外,cD2 KO 动物在旷场和自动运动室中也更活跃,在 IntelliCage 中表现出更多的探索行为。以前在海马体损伤的动物中也观察到了运动和探索行为的增加。最后,cD2 KO 小鼠对蔗糖的偏好正常,但在第二次接触到甜味溶液后才开始,而对照动物则立即表现出强烈的偏好。目前的结果表明,海马体形态异常或成人脑神经发生受损(或两者兼有)改变了突变小鼠的海马体依赖性行为,而不影响学习能力。这些结果也可能表明,成人脑神经发生参与了物种典型的行为。

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