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P3‐049: TARGETING MICROGLIAL POTASSIUM KV1.3 CHANNELS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
Author(s) -
Jin Liang,
Nicolazzo Joseph,
Norton Raymond
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.1404
Subject(s) - microglia , neuroinflammation , nitric oxide , lipopolysaccharide , pharmacology , chemistry , tumor necrosis factor alpha , potassium channel , inflammation , immunology , medicine , organic chemistry
glial cells, infiltration of peripheral leukocytes, and the release of damage-associated molecular pattern (DAMP) molecules elaborate in the brain. Under pathophysiological conditions, the activated microglia and monocytes/macrophages have been defined as either classic (pro-inflammatory; M1-like) or alternative (anti-inflammatory or protective; M2-like) phenotypes. Sirtuin 3 (SIRT3), a mitochondrial protein, is involved in energy metabolism, cell apoptosis and mitochondrial function. However, the role of SIRT3 in the microglia cell during hypometabolism is unclear. Methods:We used the in vivo model of middle cerebral artery occlusion/reperfusion (MCAO/R) and the in vitro model of oxygen glucose deprivation. We applied a Lenti-virus transfection system to overexpress and knock down the SIRT3 gene in the N9 microglial cell line. Results:We found the concentration of SIRT3 was decreased and the phenotype of the microglia switched to M1 during hypometabolism in vivo. In N9 cells with the OGD treatment, SIRT3-overexpression and SIRT3knock down regulated the transition of microglial polarization. In addition, we identified the SIRT3-LKB1-AMPK pathway played an important role in the activation and polarization of microglial cells. Conclusions:Based on our study, SIRT3 may be a good target for the therapy of hypometabolism.