Activation of BDNF signaling prevents the return of fear in female mice.


There are significant sex differences in vulnerability to develop fear-related anxiety disorders. Females exhibit twice the rate of post-traumatic stress disorder (PTSD) as males and sex differences have been observed in fear extinction learning in both humans and rodents, with a failure to inhibit fear emerging as a precipitating factor in the development of PTSD. Here we report that female mice are resistant to fear extinction, and exhibit increased DNA methylation of Bdnf exon IV and a concomitant decrease in mRNA expression within the medial prefrontal cortex. Activation of BDNF signaling by the trkB agonist 7,8-dihydroxyflavone blocks the return of fear in female mice after extinction training, and thus represents a novel approach to treating fear-related anxiety disorders that are characterized by a resistance to extinction and increased propensity for renewal.

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Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
Additional Information: © 2013 Cold Spring Harbor Laboratory Press
Publication ISSN: 1549-5485
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Related URLs: http://learnmem ... ontent/20/5/237 (Publisher URL)
PURE Output Type: Article
Published Date: 2013-04-15
Authors: Baker-andresen, D.
Law, Charlotte (ORCID Profile 0000-0003-0345-0237)
Li, Xiang
Bredy, Timothy W.



Version: Published Version

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