Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects

*The Picower Institute for Learning and Memory, Howard Hughes Medical Institute, RIKEN–MIT Neuroscience Research Center, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;
^†Department of Neurophysiology, National Institute of Mental Heath and Neurosciences, Bangalore 560029, India; and
^§National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India

Contributed by Susumu Tonegawa, June 22, 2006

Abstract

Although neurotrophins have been postulated to have antidepressant properties, their effect on anxiety is not clear. We find that transgenic overexpression of the neurotrophin BDNF has an unexpected facilitatory effect on anxiety-like behavior, concomitant with increased spinogenesis in the basolateral amygdala. Moreover, anxiogenesis and amygdalar spinogenesis are also triggered by chronic stress in control mice but are occluded by BDNF overexpression, thereby suggesting a role for BDNF signaling in stress-induced plasticity in the amygdala. BDNF overexpression also causes antidepressant effects, because transgenic mice exhibit improved performance on the Porsolt forced-swim test and an absence of chronic stress-induced hippocampal atrophy. Thus, structural changes in the amygdala and hippocampus, caused by genetic manipulation of the same molecule BDNF, give rise to contrasting effects on anxiety and depressive symptoms, both of which are major behavioral correlates of stress disorders.

Footnotes

^‡To whom correspondence may be addressed. E-mail: tonegawa{at}mit.edu or shona{at}ncbs.res.in
Author contributions: A.G., S.T., and S.C. designed research; A.G., B.S.S.R., D.N., M.T., and N.M. performed research; A.G., B.S.S.R., D.N., and S.C. analyzed data; and A.G., S.T., and S.C. wrote the paper.
Conflict of interest statement: No conflicts declared.
Abbreviations:

CIS,

chronic immobilization stress;

BLA,

basolateral amygdala;

HPA,

hypothalamic–pituitary–adrenal;

ACTH,

adrenocorticotropic hormone.