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中年小鼠的空间记忆缺陷与较低的探索活动及从属地位相关:海马神经营养因子的作用

Spatial memory deficits in middle-aged mice correlate with lower exploratory activity and a subordinate status: role of hippocampal neurotrophins.

作者信息

Francia N, Cirulli F, Chiarotti F, Antonelli A, Aloe L, Alleva E

机构信息

Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.

出版信息

Eur J Neurosci. 2006 Feb;23(3):711-28. doi: 10.1111/j.1460-9568.2006.04585.x.

DOI:10.1111/j.1460-9568.2006.04585.x
PMID:16487153
Abstract

The aim of the present work was to relate age-related individual differences in cognitive function with behavioural strategies employed in social and non-social challenges. To this purpose, the behaviour of adult (5-month-old) and middle-aged (13-month-old) CD-1 mice was scored in the social interaction, plus-maze, Morris water maze (MWM) and open-field tests. In addition, brain levels of nerve growth factor and brain-derived neurotrophic factor (BDNF) were analysed and correlated with the behaviours scored. Compared to adults, middle-aged mice showed greater anxiety in both non-social and social situations, spending less time in the open arms of the plus-maze and performing more freezing behaviour in response to aggression. Based upon their behaviour in the social interaction test, adult and middle-aged subjects were classified as dominant or subordinate and their behaviour in the open field, plus-maze and MWM tests subjected to factor analysis, taking into account age and social status. Results highlighted meaningful differences in exploratory strategies as a function of social status only in middle-aged subjects. In particular, middle-aged dominants were, overall, more explorative than same-aged subordinates, spending less time in peripheral areas and approaching more readily a novel object. Interestingly, in middle-aged mice, superior performance in the MWM task was associated with exploratory strategies exploited by dominants. At adulthood, BDNF hippocampal levels, but not specific behaviours, were positively correlated with the ability to learn a spatial task. Overall, data indicate that, in middle-aged subjects individual differences in exploratory strategies, rather than neurotrophin levels, are able to predict the degree of impairment in a spatial learning task.

摘要

本研究的目的是将认知功能方面与年龄相关的个体差异,与在社交和非社交挑战中所采用的行为策略联系起来。为此,对成年(5个月大)和中年(13个月大)的CD-1小鼠在社交互动、十字迷宫、莫里斯水迷宫(MWM)和旷场试验中的行为进行评分。此外,分析了神经生长因子和脑源性神经营养因子(BDNF)的脑内水平,并将其与所记录的行为进行关联分析。与成年小鼠相比,中年小鼠在非社交和社交情境中均表现出更高的焦虑水平,在十字迷宫的开放臂中停留时间更短,对攻击行为表现出更多的僵立行为。根据它们在社交互动试验中的行为,将成年和中年小鼠分为优势或从属类别,并对它们在旷场、十字迷宫和MWM试验中的行为进行因子分析,同时考虑年龄和社会地位。结果突出显示,仅在中年小鼠中,探索策略因社会地位不同而存在显著差异。具体而言,总体上中年优势小鼠比同龄从属小鼠更具探索性,在周边区域停留时间更短,更容易接近新物体。有趣的是,在中年小鼠中,MWM任务中的卓越表现与优势小鼠所采用的探索策略相关。在成年期,BDNF的海马水平而非特定行为,与学习空间任务的能力呈正相关。总体而言,数据表明,在中年小鼠中,探索策略的个体差异而非神经营养因子水平,能够预测空间学习任务中的损伤程度。

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