title: Dose-related effects of chronic resveratrol administration on neurogenesis, angiogenesis, and corticosterone secretion are associated with improved spatial memory retention following global cerebral ischemia.
abstract: OBJECTIVE
  The polyphenol resveratrol has shown regulatory effects on hippocampal neurogenesis, which according to the neurovascular niche hypothesis, is likely to involve stimulation of angiogenesis. In rodents, global cerebral ischemia leads to selective CA1 neuronal damage, spatial memory impairments, lasting changes in corticosterone (CORT) secretion, and increased neurogenesis. This study examined dose-related effects of 21-day RSV treatment on markers associated with neurogenesis (DCX, PSA-NCAM) and angiogenesis (CD31) in the hippocampus at short (7-day) and long-term (85-day) intervals following global ischemia. In parallel, post-ischemic and stress-induced CORT levels and spatial memory in the Morris water maze were determined.
  
  
  METHODS
  Five groups of male Wistar rats were included: sham/saline, ischemia/saline, ischemia/1 mg/kg RSV, ischemia/10 mg/kg RSV, and sham/10 mg/kg RSV. Changes in expression of plasticity markers were paralleled by assessment of basal- and stress-induced CORT secretions, and spatial memory performance.
  
  
  RESULTS
  Our findings revealed a significant attenuation of ischemia-induced DCX/PSA-NCAM expression in RSV-treated rats, whereas RSV treatment increased angiogenesis in the injured CA1 region. RSV attenuated CORT levels 3 days post-ischemia and a trend toward attenuating CORT secretion in response to 15 minutes restraint stress. Increased swimming latencies in the target quadrant during the MWM probe trial in RSV-treated ischemic rats support beneficial effects of RSV on spatial memory retention.
  
  
  CONCLUSIONS
  Our findings uncover time- and dose-related effects of RSV and global ischemia on the regulation of hippocampal plasticity. Changes in neuro- and angiogenesis are consistent with RSV neuroprotective effects, but appear independent of RSV regulatory effects on corticosterone secretion.
authors: a School of Psychology, Behavioral Neuroscience Group , University of Ottawa , Ontario , Canada.
authors: Catrinel
authors: C
authors: Girbovan
authors: a School of Psychology, Behavioral Neuroscience Group , University of Ottawa , Ontario , Canada.
authors: Pamela
authors: P
authors: Kent
authors: a School of Psychology, Behavioral Neuroscience Group , University of Ottawa , Ontario , Canada.|b Institute of Mental Health Research, University of Ottawa , Ontario , Canada.
authors: Zul
authors: Z
authors: Merali
authors: a School of Psychology, Behavioral Neuroscience Group , University of Ottawa , Ontario , Canada.
authors: Hélène
authors: H
authors: Plamondon
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D056547:CA1 Region, Hippocampal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000089662:Doublecortin Protein; D007274:Injections, Intraperitoneal; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011897:Random Allocation; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D000077185:Resveratrol; D065852:Spatial Memory / Q000187:drug effects*; D013267:Stilbenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; D013267:Stilbenes; D000077185:Resveratrol; D003345:Corticosterone
keywords: Angiogenesis; Cerebral ischemia; Corticosterone; Neurogenesis; Restraint stress; Resveratrol; Spatial memory