Aminoguanidine alleviated MMA-induced impairment of cognitive ability in rats by downregulating oxidative stress and inflammatory reaction |
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| Affiliation: | 1. Department of Medical Laboratory, Xuanwu Hospital, Beijing Children’s Hospital, Capital Medical University, PR China;2. Department of Medical Laboratory, Beijing Children’s Hospital, Capital Medical University, PR China;3. Institute of Applied Cancer Research, MD Anderson Cancer Center, USA;4. Department of Medical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China;1. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States;2. Department of Neuroscience, University of Parma Medical School, Parma, Italy;1. Rudolfstiftung Hospital, 1180 Vienna, Austria;1. School of Marine Sciences, Ningbo University, Ningbo 315211, PR China;2. Zhejiang Key Laboratory of Aquatic Germplasm Resources, Zhejiang Wanli University, Ningbo 315100, PR China;1. Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA;2. Division of Abdominal Transplantation, Department of Surgery, Stanford University, Stanford, CA;3. Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University, Stanford, CA;4. Department of Pathology, Stanford University, Stanford, CA;5. Lucile Packard Children''s Hospital at Stanford, Stanford, CA;6. Prenatal Diagnostics, Department of Obstetrics and Gynecology, University of California, San Francisco, San Francisco, CA |
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| 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. |
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| Keywords: | Methylmalonic acidemia Aminoguanidine Oxidative stress Inflammation |
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