Examination of behavioral deficits triggered by targeting Bdnf in fetal or postnatal brains of mice
Examination of behavioral deficits triggered by targeting Bdnf in fetal or postnatal brains of mice
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DOI：
10.1016/j.neuroscience.2006.06.002
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发表时间：
2006-09-29
期刊：
影响因子：
3.3
通讯作者：
Rios, M.
中科院分区：
文献类型：
--
作者：
Chan, J. P.;Unger, T. J.;Rios, M.
人类和动物研究表明脑源性神经营养因子（BDNF）与精神疾病的病因有关。它在胎儿发育期间和成年动物中与情绪调节相关的大脑边缘区域中表达。为了进一步了解BDNF在情绪调节中的作用，并区分其产前和产后功能，我们研究并对比了小鼠胎儿或产后脑中BDNF耗竭引起的行为变化。对两个相应的BDNF条件性基因敲除小鼠品系进行一系列行为测试，评估运动、抑郁、攻击和焦虑相关行为。我们发现这两种突变株系在光照和黑暗周期中都非常活跃，而且攻击性很强。它们在悬尾试验中也表现出抑郁样表型，但在强迫游泳试验中没有。有趣的是，从胎儿大脑中耗尽BDNF对攻击性和抑郁样行为有更明显的影响，并导致内侧额叶皮质中5-HT 2A受体含量的不足，突出了这种神经营养因子在发育过程中的重要性。我们的结论是，表达BDNF的出生前和出生后是必不可少的正常调制行为的神经回路在成年动物。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Human and animal studies have implicated brain-derived neurotrophic factor (BDNF) in the etiology of psychiatric disorders. It is expressed in limbic regions of the brain associated with the regulation of emotionality during fetal development and in the adult animal. To further our understanding of the role of BDNF in the modulation of mood and to distinguish its prenatal and postnatal functions, we investigated and contrasted behavioral changes elicited by its depletion from fetal or postnatal brains of mice. Two corresponding lines of BDNF conditional knockout mice were subjected to a battery of behavioral tests assessing locomotor, depressive, aggressive and anxiety-related behaviors. We found that both lines of mutants were dramatically hyperactive during the light and dark cycles and hyperaggressive. They also exhibited a depression-like phenotype in the tail suspension test but not in the forced swim test. Interestingly, depletion of BDNF from the fetal brain had more pronounced effects on aggressive and depressive-like behaviors and led to deficits in 5-HT2A receptor content in the medial frontal cortex, highlighting the importance of this neurotrophin during development. We conclude that expression of BDNF both pre- and postnatally is essential for normal modulation of behavior by neural circuits in the adult animal. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.