Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects.
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.
Govindarajan
Arvind
A
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, USA.
Rao
B S Shankaranarayana
BS
Nair
Deepti
D
Trinh
Mimi
M
Mawjee
Nadya
N
Tonegawa
Susumu
S
Chattarji
Sumantra
S
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism*; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D001284:Atrophy; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013312:Stress, Physiological / Q000139:chemically induced
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor