PT - JOURNAL ARTICLE AU - Alam, Mahabub Maraj AU - Zhao, Xiao-Feng AU - Liao, Yuan AU - Mathur, Ramkumar AU - McCallum, Sarah E. AU - Mazurkiewicz, Joseph E. AU - Adamo, Matthew A. AU - Feustel, Paul AU - Belin, Sophie AU - Poitelon, Yannick AU - Zhu, Xinjun Cindy AU - Huang, Yunfei TI - Deficiency of Microglial Autophagy Increases the Density of Oligodendrocytes and Susceptibility to Severe Forms of Seizures AID - 10.1523/ENEURO.0183-20.2021 DP - 2021 Jan 01 TA - eneuro PG - ENEURO.0183-20.2021 VI - 8 IP - 1 4099 - http://www.eneuro.org/content/8/1/ENEURO.0183-20.2021.short 4100 - http://www.eneuro.org/content/8/1/ENEURO.0183-20.2021.full SO - eNeuro2021 Jan 01; 8 AB - Excessive activation of mTOR in microglia impairs CNS homeostasis and causes severe epilepsy. Autophagy constitutes an important part of mTOR signaling. The contribution of microglial autophagy to CNS homeostasis and epilepsy remains to be determined. Here, we report that ATG7KO mice deficient for autophagy in microglia display a marked increase of myelination markers, a higher density of mature oligodendrocytes (ODCs), and altered lengths of the nodes of Ranvier. Moreover, we found that deficiency of microglial autophagy (ATG7KO) leads to increased seizure susceptibility in three seizure models (pilocarpine, kainic acid, and amygdala kindling). We demonstrated that ATG7KO mice develop severe generalized seizures and display nearly 100% mortality to convulsions induced by pilocarpine and kainic acid. In the amygdala kindling model, we observed significant facilitation of contralateral propagation of seizures, a process underlying the development of generalized seizures. Taken together, our results reveal impaired microglial autophagy as a novel mechanism underlying altered homeostasis of ODCs and increased susceptibility to severe and fatal generalized seizures.