title: The effects of valsartan on cognitive deficits induced by aluminum trichloride and d-galactose in mice.
abstract: OBJECTIVE
  Valsartan has been reported to reduce brain beta-amyloid protein levels and improve spatial learning in the Tg2576 transgenic mouse model of Alzheimer's disease (AD). However, the exact mechanism of neuroprotective effects of valsartan has not been properly studied especially in cholinergic function and oxidative damage, the essential factors that undergo impairment in AD. Therefore, the present study examined the effects of valsartan on memory impairment, cholinergic dysfunction, and oxidative stress in aluminum trichloride (AlCl3) and d-galactose (d-gal)-induced experimental sporadic dementia of Alzheimer's type.
  
  
  METHODS
  Valsartan was administered intragastrically (i.g.) (20 mg/kg/day) for 60 days after mice were given AlCl3 (10 mg/kg/day) and d-gal (150 mg/kg/day) intraperitoneally (i.p.) once daily for 90 days. Then, memory function was evaluated by Morris water maze test. Acetylcholinesterase (AChE), superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) level in cortex and hippocampus were also assessed with biochemical technique.
  
  
  RESULTS
  Chronic administration of valsartan not only improved learning and memory but also restored the elevation of AChE activity induced by AlCl3 and d-gal in cortex and hippocampus. In addition, valsartan significantly restored SOD and GSH-Px activities and reduced MDA level in cortex and hippocampus indicating attenuation of oxidative stress.
  
  
  CONCLUSIONS
  Our results indicate that valsartan prevents AlCl3- and d-gal-induced cognitive decline partly to restore cholinergic function and attenuate oxidative damage. These findings further support the potential of valsartan to be used in AD treatment.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Yang
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Hu
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shi
authors.forename: Gai-Feng
authors.initials: GF
authors.lastname: Feng
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qian
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D002712:Chlorides; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D003704:Dementia; D004195:Disease Models, Animal; D005690:Galactose; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D018697:Nootropic Agents; D013777:Tetrazoles; D000077410:Aluminum Chloride; D008315:Malondialdehyde; D000068756:Valsartan; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D014633:Valine; D005690:Galactose
keywords: Acetylcholinesterase,; Alzheimer's disease; Cognitive deficits,; Oxidative stress,; Valsartan,