Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons.

Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons.
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DOI:
10.1002/hipo.20744
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发表时间:
2011-03
期刊:
影响因子:
3.5
通讯作者:
McEwen, B. S.
McEwen, B. S.
中科院分区:
医学3区
文献类型:
--
作者:
Magarinos, A. M.;Li, C. J.;Toth, J. Gal;Bath, K. G.;Jing, D.;Lee, F. S.;McEwen, B. S.

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慢性束缚应激(CRS)诱导重塑(即,收缩和简化)的顶树突的海马CA 3锥体神经元在大鼠中,表明海马内的连接可以受到长期的压力挑战。由于神经元树突分支和突触连接的结构维持需要神经营养支持,我们研究了脑源性神经营养因子(BDNF)的潜在作用,BDNF是一种在海马中富集并以活动依赖性方式从神经元释放的神经营养因子,作为应激诱导的树突重塑的介质。对Golgi浸渍的海马切片的分析显示,野生型(WT)C57 BL/6雄性小鼠对三周CRS的反应显示出与之前描述的大鼠相似的CA 3顶端树突重塑。单倍不足的BDNF小鼠(BDNF±)没有表现出这种重塑,但是,即使没有CRS,它们也呈现出更短和简化的CA 3顶端树突状动脉,就像在应激的WT小鼠中观察到的那样。此外,未应激的BDNF±小鼠显示总海马体积显著减少。CA 1区锥体神经元的树突分支不受CRS或基因型的影响。然而,仅在WT小鼠中,CRS诱导CA 1和CA 3顶树突中树突棘形状亚型的密度变化。这些结果表明,BDNF在维持海马神经元的树突和棘形态以及海马结构的相关体积方面具有复杂的作用。CRS不能改变BDNF±小鼠中CA 3锥体神经元的树突结构,这表明BDNF在介导海马树突重塑中的间接(可能是允许的)作用。
Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the hippocampus and released from neurons in an activity-dependent manner, as a mediator of the stress-induced dendritic remodeling. The analysis of Golgi-impregnated hippocampal sections revealed that wild type (WT) C57BL/6 male mice showed a similar CA3 apical dendritic remodeling in response to three weeks of CRS to that previously described for rats. Haploinsufficient BDNF mice (BDNF±) did not show such remodeling, but, even without CRS, they presented shorter and simplified CA3 apical dendritic arbors, like those observed in stressed WT mice. Furthermore, unstressed BDNF± mice showed a significant decrease in total hippocampal volume. The dendritic arborization of CA1 pyramidal neurons was not affected by CRS or genotype. However, only in WT mice, CRS induced changes in the density of dendritic spine shape subtypes in both CA1 and CA3 apical dendrites. These results suggest a complex role of BDNF in maintaining the dendritic and spine morphology of hippocampal neurons and the associated volume of the hippocampal formation. The inability of CRS to modify the dendritic structure of CA3 pyramidal neurons in BDNF± mice suggests an indirect, perhaps permissive, role of BDNF in mediating hippocampal dendritic remodeling.
DOI: 10.1073/pnas.0709102105
发表时间: 2008-03-25
影响因子: 11.1
作者:
Jeanneteau, Freddy;Garabedian, Michael J.;Chao, Moses V.
通讯作者: Chao, Moses V.
DOI: 10.1038/mp.2008.119
发表时间: 2009-08-01
影响因子: 11
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发表时间: 2004-01-01
期刊: HIPPOCAMPUS
影响因子: 3.5
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DOI: 10.1016/j.molbrainres.2003.11.002
发表时间: 2004-02-05
期刊: MOLECULAR BRAIN RESEARCH
影响因子: --
作者:
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DOI: 10.1210/endo-117-5-1803
发表时间: 1985-01-01
期刊: ENDOCRINOLOGY
影响因子: 4.8
作者:
FUXE, K;WIKSTROM, AC;GUSTAFSSON, JA
通讯作者: GUSTAFSSON, JA