Hippocampal brain-derived neurotrophic factor mediates recovery from chronic stress-induced spatial reference memory deficits
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 stres...
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| Published in: | The European journal of neuroscience Vol. 40; no. 9; pp. 3351 - 3362 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Oxford
Blackwell Publishing Ltd
01-11-2014
Blackwell |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 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.
Chronic restraint stress‐induced deficits in spatial learning and memory can improve following a post‐stress recovery period. Here we investigated BDNF as a potential mediator of the recovery process. It was found that down‐regulating hippocampal BDNF disrupted the recovery of spatial reference memory demonstrating that hippocampal BDNF is necessary for the recovery from stress‐induced hippocampal‐dependent spatial memory deficits. |
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| Bibliography: | Arizona Biomedical Research Commission ark:/67375/WNG-R71Z5GG9-7 National Science Foundation Graduate Research Fellowship Program - No. DGE-1311230 NIH IMSD program - No. R25GM099650 istex:4478DD21AE14D0B8FC03C05D96B1B2176820001A ArticleID:EJN12703 Arizona State University's College of Liberal Arts and Sciences ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0953-816X 1460-9568 |
| DOI: | 10.1111/ejn.12703 |