Affiliation:
1. Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine , 138 Xianlin Avenue, Nanjing, Jiangsu 210023 , China
2. Department of Toxicology, School of Public Health, Nanjing Medical University , 101 Longmian Avenue, Nanjing, Jiangsu 211166 , China
Abstract
Abstract
Previously, we found that dCA1 A1-like polarization of astrocytes contributes a lot to the spatial memory deficit in methamphetamine abstinence mice. However, the underlying mechanism remains unclear, resulting in a lack of promising therapeutic targets. Here, we found that methamphetamine abstinence mice exhibited an increased M1-like microglia and A1-like astrocytes, together with elevated levels of interleukin 1α and tumor necrosis factor α in dCA1. In vitro, the M1-like BV2 microglia cell medium, containing high levels of Interleukin 1α and tumor necrosis factor α, elevated A1-like polarization of astrocytes, which weakened their capacity for glutamate clearance. Locally suppressing dCA1 M1-like microglia activation with minocycline administration attenuated A1-like polarization of astrocytes, ameliorated dCA1 neurotoxicity, and, most importantly, rescued spatial memory in methamphetamine abstinence mice. The effective time window of minocycline treatment on spatial memory is the methamphetamine exposure period, rather than the long-term methamphetamine abstinence.
Funder
National Natural Science Foundation of China
Traditional Chinese Medicine Technology Development Plan of Jiangsu Province
Natural Science Foundation of the Higher Education Institutions of Jiangsu Province
Publisher
Oxford University Press (OUP)