title: Hippocampal brain-derived neurotrophic factor mediates recovery from chronic stress-induced spatial reference memory deficits.
abstract: Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain-derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the dorsal hippocampal cornu ammonis (CA)3 region with an adeno-associated viral vector containing the sequence for a short hairpin RNA (shRNA) directed against BDNF or a scrambled sequence (Scr). Rats were then chronically restrained (wire mesh, 6 h/day for 21 days) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trials. Rats in the Str-Imm group, regardless of adeno-associated viral contents, committed more errors in the spatial reference memory domain on the single retention trial during day 3 than did the non-stressed controls. Importantly, the typical improvement in spatial memory following the recovery from chronic stress was blocked with the shRNA against BDNF, as Str-Rec-shRNA performed worse on the RAWM compared with the non-stressed controls or Str-Rec-Scr. The stress effects were specific for the reference memory domain, but knockdown of hippocampal BDNF in unstressed controls briefly disrupted spatial working memory as measured by repeated entry errors on day 2 of training. These results demonstrated that hippocampal BDNF was necessary for the recovery from stress-induced hippocampal-dependent spatial memory deficits in the reference memory domain.
authors.affiliation: Behavioral Neuroscience, Department of Psychology, Arizona State University, Box 1104, Tempe, AZ, 85287-1104, USA.
authors.forename: J Bryce
authors.initials: JB
authors.lastname: Ortiz
authors.forename: Coy M
authors.initials: CM
authors.lastname: Mathewson
authors.forename: Ann N
authors.initials: AN
authors.lastname: Hoffman
authors.forename: Paul D
authors.initials: PD
authors.lastname: Hanavan
authors.forename: Ernest F
authors.initials: EF
authors.lastname: Terwilliger
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Conrad
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D056654:CA3 Region, Hippocampal / Q000378:metabolism*; D015536:Down-Regulation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D065852:Spatial Memory / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: neuroplasticity; radial arm water maze; rat; recovery of function; resilience; short hairpin RNA