465-P: AGE Precursor Methylglyoxal May Result in Behavioral Pattern of Neurological Disorders in Animal Mouse Model

Abstract

Purpose of the study: Diabetes mellitus (DM) is characterized by chronic hyperglycemia and diabeticcomplications. Impairment in neuropsychological functioning in DM patients is shownin clinical studies. Patients with DM have a higher risk of developing neurologicaldisorders, including Parkinson’s disease (PD) , depression, and anxiety. Symptoms ofthese diseases are observed in diabetic animal models and in population-based studies.DM-induced activation of stress responses in the central nervous system (CNS) such asoxidative stress and neuroinflammation may lead to various neurological disorders.Abnormal accumulation of methylglyoxal (MG) , one of the most reactive advancedglycation end-product (AGE) precursors, is found in the serum of DM patients. As MGis reported to induce brain cells impairment in the CNS, the effect of MG leading tosubsequent symptoms of the three neurological disorders was investigated. Methods: C57BL/6 mice were treated with MG solution (60mg/kg) or sham control byintraperitoneal injection for weeks. Rotarod test, open-field test (OFT) , and forcedswim test (FST) were used to examine the motor coordination, anxiety-like behavior,and depressive-like behavior of mice respectively. Corresponding parameters of thetests were measured and recorded. Summary of the results: In the rotarod test, significantly reduced latency to fall off was observed in the MG-treated group (74.1 ± 5.33) than that in the control group (92.9 ± 5.80) . In the OFT,significantly reduced total traveled distance (285 ± 1.01) was observed in the MG-treated group than that in the control group (13.4 ± 1.48) . In the FST, significantlyincreased percentage of immobile time was observed in the MG-treated group (77.6 ±2.19) than that in the control group (68.7 ± 2.42) . Conclusions: MG could induce symptoms of PD, depression, and anxiety in mice. MG may play arole in the dysfunction of brain cells and dysregulation of CNS resulting in neurologicaldisorders Disclosure K.Yue: None.