RT Journal Article
SR Electronic
T1 Deficiency of Microglial Autophagy Increases the Density of Oligodendrocytes and Susceptibility to Severe Forms of Seizures
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0183-20.2021
DO 10.1523/ENEURO.0183-20.2021
VO 8
IS 1
A1 Alam, Mahabub Maraj
A1 Zhao, Xiao-Feng
A1 Liao, Yuan
A1 Mathur, Ramkumar
A1 McCallum, Sarah E.
A1 Mazurkiewicz, Joseph E.
A1 Adamo, Matthew A.
A1 Feustel, Paul
A1 Belin, Sophie
A1 Poitelon, Yannick
A1 Zhu, Xinjun Cindy
A1 Huang, Yunfei
YR 2021
UL http://www.eneuro.org/content/8/1/ENEURO.0183-20.2021.abstract
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.