title: Lycopene attenuates diabetes-associated cognitive decline in rats.
abstract: Diabetes-induced learning and memory impairment, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involve direct neuronal damage caused by intracellular glucose. The present study was designed to investigate the effect of lycopene, a potent anti-oxidant and anti-inflammatory molecule, on cognitive functions, oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats. Cognitive functions were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 1.8 fold in the cerebral cortex of diabetic rats. There was about 2 fold and 2.2 fold rise in thiobarbituric acid-reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Non-protein thiol levels and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Total nitric oxide levels in cerebral cortex and hippocampus was increased by 2.4 fold and 2 fold respectively. Serum tumor necrosis factor-alpha, an inflammatory marker, was found to increase by 8 fold in diabetic rats. Chronic treatment with lycopene (1, 2 and 4 mg/kg; p.o.) significantly and dose dependently attenuated cognitive deficit, increased acetylcholinesterase activity, oxidative-nitrosative stress and inflammation in diabetic rats. The results emphasize the involvement of oxidative-nitrosative stress and peripheral inflammation in the development of cognitive impairment in diabetic animals and point towards the therapeutic potential of lycopene in diabetes-induced learning and memory impairment.
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160 014, India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Kuhad
authors.forename: Richa
authors.initials: R
authors.lastname: Sethi
authors.forename: Kanwaljit
authors.initials: K
authors.lastname: Chopra
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D002338:Carotenoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D000077276:Lycopene; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D013438:Sulfhydryl Compounds; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002338:Carotenoids; D002374:Catalase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D000077276:Lycopene