title: Aminoguanidine alleviated MMA-induced impairment of cognitive ability in rats by downregulating oxidative stress and inflammatory reaction.
abstract: Methylmalonic acidemia (MMA) is the most common organic acidemia in childhood. Many "treated" patients continued to display various degrees of mental retardation and psychomotor delay, which could be caused by brain damage from elevated oxidative stress. Aminoguanidine (AG), a synthetic antioxidant, was tested in a MMA rat model for its potential therapeutic effects on memory impairment. The effects of AG on MMA-induced cognitive impairment in Wistar rats were evaluated with Morris Water Maze. The levels of nerve cell apoptosis and microglial activation were investigated to illustrate the mechanisms of the improvement of cognition with AG treatment in MMA rats. To further explore the mechanism of neuroprotection induced by AG, several biomarkers including free radicals and inflammatory cytokines in the hippocampus were quantified. The results showed that the rats treated with AG exhibited better neurological behavior performances than MMA model rats. The AG-treated rats had a decreased level of apoptosis of the hippocampal neurons, which could be the structural basis of the observed neural behavior protection. In addition, AG treatment significantly inhibited the activation of microglia. The AG-treated rats had decreased levels of IL-1β, IL-6, TNF-α, NO, malonaldehyde and iNOS activities in the hippocampus. The level of glutathione and superoxide dismutase activity in the hippocampus of the AG-treated rats increased significantly. In conclusion, AG could alleviate the MMA-induced cognitive impairment via down-regulating of oxidative stress and inflammatory reaction and provide a basis as a therapeutic potential against MMA-induced cognitive impairment.
authors.affiliation: Department of Medical Laboratory, Xuanwu Hospital, Beijing Children's Hospital, Capital Medical University, PR China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Medical Laboratory, Beijing Children's Hospital, Capital Medical University, PR China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Song
authors.affiliation: Institute of Applied Cancer Research, MD Anderson Cancer Center, USA.
authors.forename: Ze
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Department of Medical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China. Electronic address: Pcw1905@126.com.
authors.forename: Peichang
authors.initials: P
authors.lastname: Wang
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016207:Cytokines; D006146:Guanidines; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine
keywords: Aminoguanidine; Inflammation; Methylmalonic acidemia; Oxidative stress