| Autor: |
Wang DX; Institute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China., Chen AD; Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China., Wang QJ; Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.; Key Laboratory of Brain Functional Genomics, Ministry of Education, School of Life Science, East China Normal University, Shanghai, PR China., Xin YY; Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China., Yin J; Institute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China., Jing YH; Institute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.; Key Laboratory of Preclinical Study for New Drugs of Gansu province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China. |
| Abstrakt: |
Rotenone is a mitochondrial complex I inhibitor, which can cause the death of dopaminergic (DA) neurons and Parkinson's disease (PD). Currently, whether metformin has a protective effect on neurotoxicity induced by rotenone is unclear. The purpose of this study was to evaluate the potential protective effect of metformin against rotenone-induced neurotoxicity. PD animal model was established by unilateral rotenone injection into the right substantia nigra (SN) of C57BL/6 mice. The behavioral tests were performed by rotarod test and cylinder test. The numbers of TH-positive neurons and Iba-1 positive microglia in the SN were investigated by immunohistochemical staining. The mRNA levels of proinflammatory cytokines (TNF-α and IL-1β) and molecules involved in endoplasmic reticulum (ER) stress (ATF4, ATF6, XBP1, Grp78, and CHOP) in the midbrain were detected by Quantitative real-time PCR. This study showed that 50 mg/kg metformin given orally daily, beginning 3 d before rotenone injection and continuing for 4 weeks following rotenone injection, significantly ameliorated dyskinesia, increased the number of TH-positive neurons, and mitigated the activation of microglia in the SN in rotenone-induced PD mice. Furthermore, 50 mg/kg metformin markedly downregulated the expression of proinflammatory cytokines (TNF-α and IL-1β) and ER stress-related genes (ATF4, ATF6, XBP1, Grp78, and CHOP) in rotenone-induced PD mice. Metformin has a protective effect on DA neurons against rotenone-induced neurotoxicity through inhibiting neuroinflammation and ER stress in PD mouse model. |
