TY - JOUR T1 - Deficiency of Microglial Autophagy Increases the Density of Oligodendrocytes and Susceptibility to Severe Forms of Seizures JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0183-20.2021 VL - 8 IS - 1 SP - ENEURO.0183-20.2021 AU - Mahabub Maraj Alam AU - Xiao-Feng Zhao AU - Yuan Liao AU - Ramkumar Mathur AU - Sarah E. McCallum AU - Joseph E. Mazurkiewicz AU - Matthew A. Adamo AU - Paul Feustel AU - Sophie Belin AU - Yannick Poitelon AU - Xinjun Cindy Zhu AU - Yunfei Huang Y1 - 2021/01/01 UR - http://www.eneuro.org/content/8/1/ENEURO.0183-20.2021.abstract N2 - 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. ER -