title: Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats.
abstract: OBJECTIVE
  To investigate the effects of resveratrol on cognitive impairment in streptozotocin (STZ)-induced diabetic rats and to explore the mechanisms of that phenomenon.
  
  
  METHODS
  Sixty healthy male Sprague Dawley rats were randomly divided into four groups: normal control group (Con group, n = 15), Res group (normal Sprague Dawley rats treated with resveratrol, n = 15), diabetes mellitus group (DM group, n = 15) and DM + Res group (diabetic rats treat with resveratrol, n = 15). Streptozotocin (STZ) was injected intraperitoneally to establish the diabetic model. One week after diabetic model induction, the animals in the Res group and the DM + Res group received resveratrol intraperitoneally once a day for consecutive 4 weeks. The Morris water maze test was applied to assess the effect of resveratrol on learning and memory. To explore the mechanisms of resveratrol on cognition, we detected the protein expression levels of Caspase-3, Bcl-2, Bax, NMDAR1 (N-Methyl-d-Aspartate receptor) and BDNF (Brain Derived Neurotrophic Factor) via western blotting analysis.
  
  
  RESULTS
  Resveratrol has no obvious effect on normal SD rats. Compared to Con group, cognitive ability was significantly impaired with increased expression of Caspase-3, Bax and down-regulation of Bcl-2, NMDAR1 and BDNF in diabetic rats. By contrast, resveratrol treatment improved the cognitive decline. Evidently, resveratrol treatment reversed diabetes-induced changes of protein expression.
  
  
  CONCLUSIONS
  Resveratrol significantly ameliorates cognitive decline in STZ-induced diabetic model rats. The potential mechanism underlying the protective effect could be attributed to the inhibition of hippocampal apoptosis through the Bcl-2, Bax and Caspase-3 signaling pathways and improvement of synaptic dysfunction. BDNF may also play an indispensable role in this mechanism.
authors.affiliation: Department of Neurology, Tianjin Huanhu Hospital, Jinnan District, Tianjin, PR China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Tian
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.forename: Yuying
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*; D013311:Streptozocin; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D053148:Caspase 3; D016194:Receptors, N-Methyl-D-Aspartate; D000077185:Resveratrol; D013267:Stilbenes; D013311:Streptozocin; D051028:bcl-2-Associated X Protein