BDNF and TrkB Mediate the Improvement from Chronic Stress-induced Spatial Memory Deficits and CA3 Dendritic Retraction

J. Bryce Ortiz, Julia M. Anglin, Eshaan J. Daas, Pooja R. Paode, Kenji Nishimura, Cheryl Conrad

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The brain is capable of improving from a chronically stressed state. The hippocampus in particular appears to “recover” from chronic stress-induced morphological and functional deficits following a post-stress rest period of several weeks. We previously found that hippocampal brain-derived neurotrophic factor (BDNF) was necessary for spatial ability to improve following a post-stress rest period. The following studies are the first to investigate the involvement of BDNF and its TrkB receptor on the recovery process following the end of chronic stress, as it pertains to hippocampal dendritic retraction and spatial memory deficits. In the first study, hippocampal BDNF was downregulated via RNA interference and then hippocampal CA3 and CA1 dendritic complexity were evaluated following chronic stress and a post-stress rest period in male Sprague–Dawley rats. Downregulating hippocampal BDNF prevented the enhancement of CA3 apical dendritic complexity following the rest period. Moreover, chronic stress and downregulated BDNF in the post-stress rest group led to regionally specific enhancements in CA1 dendritic complexity. In the second study, we tested whether the TrkB receptor was involved by administering daily systemic injections of ANA-12, a TrkB receptor antagonist, during the three-week post-stress rest period. ANA-12 prevented the improvement in spatial ability and CA3 apical dendritic complexity following the post-stress rest period. These data demonstrate that hippocampal BDNF acting via its TrkB receptor is necessary during the post-stress rest period in order to improve the impaired hippocampal structural and cognitive outcomes that occur in response to chronic stress.

Original languageEnglish (US)
Pages (from-to)330-346
Number of pages17
JournalNeuroscience
Volume388
DOIs
StatePublished - Sep 15 2018

Keywords

  • BDNF
  • chronic stress
  • dendrites
  • hippocampus
  • spatial memory
  • TrkB

ASJC Scopus subject areas

  • Neuroscience(all)

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