title: Activation of BDNF signaling prevents the return of fear in female mice.
abstract: 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.
authors.affiliation: Psychiatric Epigenomics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Danay
authors.initials: D
authors.lastname: Baker-Andresen
authors.forename: Charlotte R
authors.initials: CR
authors.lastname: Flavell
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Bredy
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D004195:Disease Models, Animal; D005091:Exons; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005260:Female; D047309:Flavones / Q000494:pharmacology; D051379:Mice; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: C485383:6,7-dihydroxyflavone; D019208:Brain-Derived Neurotrophic Factor; D047309:Flavones; D012333:RNA, Messenger