Ferulic acid attenuated cognitive deficits and increase in carbonyl proteins induced by buthionine-sulfoximine in mice.
beta-Amyloid peptide (Abeta), the major constituent of the senile plaques observed in the brains of Alzheimer's disease patients, is cytotoxic to neurons and plays a central role in the pathogenesis of this disease. Previous studies have suggested that oxidative stress is involved in the mechanisms of Abeta-induced neurotoxicity in vivo. Here, we used a mouse model of brain dysfunction induced by dl-buthionine-(S,R)-sulfoximine (BSO: 3micromol/3microL/mouse, i.c.v.), an inhibitor of glutathione synthesis. In the novel object recognition test, we found impairments of exploratory preference in the retention trial but not the training trial 24h after BSO treatment, suggesting that BSO produces cognitive dysfunction in mice. In the forebrain of this model, we observed increase in carbonyl protein levels, an index of biochemical oxidative damage of proteins, compared to vehicle-treated mice. Pretreatment with ferulic acid (5mg/kg, s.c.) once a day for 6 days inhibited the induction of deficits in memory and increase in carbonyl protein levels by BSO. These findings suggest that pretreatment with FA may attenuate the memory deficits and increase the carbonyl protein levels induced by BSO in mice.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. mamiya@ccmfs.meijo-u.ac.jp
Takayoshi
T
Mamiya
Mitsuo
M
Kise
Keiko
K
Morikawa
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019328:Buthionine Sulfoximine; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D003373:Coumaric Acids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D050050:Protein Carbonylation / Q000187:drug effects*
D003373:Coumaric Acids; D016166:Free Radical Scavengers; D019328:Buthionine Sulfoximine; C004999:ferulic acid