Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress

被引:229
作者
Schloesser, R. J. [2 ]
Lehmann, M. [1 ]
Martinowich, K. [2 ]
Manji, H. K. [2 ]
Herkenham, M. [1 ]
机构
[1] NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA
[2] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA
关键词
hippocampal neurogenesis; social stress; environmental enrichment; dentate gyrus; anxiety; depression; DENTATE GYRUS; HIPPOCAMPAL NEUROGENESIS; ANTIDEPRESSANT TREATMENT; LEARNED HELPLESSNESS; CELL-PROLIFERATION; PATTERN SEPARATION; DEPRESSIVE-ILLNESS; ANIMAL-MODELS; RAT; BRAIN;
D O I
10.1038/mp.2010.34
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The subgranular zone of the adult hippocampal dentate gyrus contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by exposure to enriched environments. These observations suggest the existence of a link between hippocampal neurogenesis, stress-induced behavioral changes, and the beneficial effects of enriched environment. To show causality, we subjected transgenic mice with conditionally suppressed neurogenesis to psychosocial stress followed by environmental enrichment. First, we showed that repeated social defeat coupled with chronic exposure to an aggressor produces robust and quantifiable indices of submissive and depressive-like behaviors; second, subsequent exposure to an enriched environment led to extinction of the submissive phenotype, while animals exposed to an impoverished environment retained the submissive phenotype; and third, enrichment was not effective in reversing the submissive and depressive-like behaviors in transgenic mice lacking neurogenesis. Our data show two main findings. First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis. Molecular Psychiatry (2010) 15, 1152-1163; doi:10.1038/mp.2010.34; published online 23 March 2010
引用
收藏
页码:1152 / 1163
页数:12
相关论文
共 55 条
[1]   Computational Influence of Adult Neurogenesis on Memory Encoding [J].
Aimone, James B. ;
Wiles, Janet ;
Gage, Fred H. .
NEURON, 2009, 61 (02) :187-202
[2]   CHEMICAL + ANATOMICAL PLASTICITY OF BRAIN - CHANGES IN BRAIN THROUGH EXPERIENCE DEMANDED BY LEARNING THEORIES ARE FOUND IN EXPERIMENTS WITH RATS [J].
BENNETT, EL ;
KRECH, D ;
DIAMOND, MC ;
ROSENZWEIG, MR .
SCIENCE, 1964, 146 (364) :610-+
[3]   Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior [J].
Bergami, Matteo ;
Rimondini, Roberto ;
Santi, Spartaco ;
Blum, Robert ;
Goetz, Magdalena ;
Canossa, Marco .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (40) :15570-15575
[4]   INTRAHIPPOCAMPAL COLCHICINE ALTERS HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE AND HIPPOCAMPAL STEROID-RECEPTOR MESSENGER-RNA IN RAT-BRAIN [J].
BRADY, LS ;
LYNN, AB ;
WHITFIELD, HJ ;
KIM, H ;
HERKENHAM, M .
NEUROENDOCRINOLOGY, 1992, 55 (02) :121-133
[5]   Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis [J].
Brown, J ;
Cooper-Kuhn, CM ;
Kempermann, G ;
Van Praag, H ;
Winkler, J ;
Gage, FH ;
Kuhn, HG .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2003, 17 (10) :2042-2046
[6]   Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene [J].
Caspi, A ;
Sugden, K ;
Moffitt, TE ;
Taylor, A ;
Craig, IW ;
Harrington, H ;
McClay, J ;
Mill, J ;
Martin, J ;
Braithwaite, A ;
Poulton, R .
SCIENCE, 2003, 301 (5631) :386-389
[7]   Rearing environmental enrichment in two inbred strains of mice:: 1.: Effects on emotional reactivity [J].
Chapillon, P ;
Manneché, C ;
Belzung, C ;
Caston, J .
BEHAVIOR GENETICS, 1999, 29 (01) :41-46
[8]   A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation [J].
Clelland, C. D. ;
Choi, M. ;
Romberg, C. ;
Clemenson, G. D., Jr. ;
Fragniere, A. ;
Tyers, P. ;
Jessberger, S. ;
Saksida, L. M. ;
Barker, R. A. ;
Gage, F. H. ;
Bussey, T. J. .
SCIENCE, 2009, 325 (5937) :210-213
[9]   Neurogenesis-Dependent and -Independent Effects of Fluoxetine in an Animal Model of Anxiety/Depression [J].
David, Denis J. ;
Samuels, Benjamin Adam ;
Rainer, Quentin ;
Wang, Jing-Wen ;
Marsteller, Douglas ;
Mendez, Indira ;
Drew, Michael ;
Craig, Douglas A. ;
Guiard, Bruno P. ;
Guilloux, Jean-Philippe ;
Artymyshyn, Roman P. ;
Gardier, Alain M. ;
Gerald, Christophe ;
Antonijevic, Irina A. ;
Leonardo, E. David ;
Hen, Rene .
NEURON, 2009, 62 (04) :479-493
[10]  
Delaney CL, 1996, J NEUROSCI, V16, P6908