BDNF and TrkB Mediate the Improvement from Chronic Stress-induced Spatial Memory Deficits and CA3 Dendritic Retraction. (15th September 2018)

• Record Type: Journal Article
• Authors: Ortiz, J. Bryce; Anglin, Julia M.; Daas, Eshaan J.; Paode, Pooja R.; Nishimura, Kenji; Conrad, Cheryl D.
• Is Part Of: Neuroscience. Volume 388(2018)
• Page Start: 330
• Page End: 346
• Publication Date: 2018-09-15
• Subjects: AAV adeno-associated viral vector -- ANOVA analysis of variance -- BDNF brain-derived neurotrophic factor -- CA cornu ammonis -- CON-ANA controls injected with ANA-12 -- CON-Scr controls infused with a scrambled viral vector sequence -- CON-Veh controls injected with vehicle -- eGFP enhanced green fluorescent protein -- LS long-shaft -- OF open field -- OP object placement -- RAWM radial arm water maze -- RNA ribonucleic acid -- SS short-shaft -- STR-I chronic stress behaviorally tested immediately (within days) after stress ended -- STR-R-Scr chronic stress given a post-stress rest period and infused with a scrambled viral vector -- STR-R-shRNA chronic stress given a post-stress rest period and infused with a viral vector targeted against BDNF RNA -- STR-R-ANA chronic stress given a post-stress rest period and injected with ANA-12 -- STR-R-Veh chronic stress given a post-stress rest period and injected with vehicle -- TrkB tropomyosin receptor kinase B; chronic stress -- BDNF -- TrkB -- dendrites -- hippocampus -- spatial memory; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.07.049
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Stress-induced deficits in spatial ability and diminished hippocampal dendritic complexity improve after a rest period. Hippocampal BDNF is required for hippocampal CA3 dendritic complexity to improve following a post-stress rest period. TrkB antagonism during the rest period prevents improvements in spatial ability and hippocampal dendritic complexity. BDNF/TrkB is required in the hippocampus, during the rest period for hippocampal structure and function to improve. 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.