Open AccessRapamycin prevents acute dendritic injury following seizures
Author(s) -
Guo Dongjun,
Zeng Linghui,
Zou Jia,
Chen Linglin,
Rensing Nicholas,
Wong Michael
Publication year - 2016
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.284
Subject(s) - cofilin , dendritic spine , mtorc1 , medicine , microbiology and biotechnology , epileptogenesis , epilepsy , neuroscience , actin cytoskeleton , pharmacology , signal transduction , cytoskeleton , biology , pi3k/akt/mtor pathway , hippocampal formation , biochemistry , cell
Objective Seizures cause acute structural changes in dendrites, which may contribute to cognitive deficits that occur in epilepsy patients. Disruption of the actin cytoskeleton of dendrites likely mediates the structural changes following seizures, but the upstream signaling mechanisms activated by synchronized physiological activity to cause seizure‐induced dendritic injury are not known. In this study, we test the hypothesis that the mechanistic target of rapamycin complex 1 ( mTORC 1) pathway triggers structural changes in dendrites in response to seizures. Methods In vivo multiphoton imaging was performed in transgenic mice expressing green fluorescent protein in cortical neurons. The effect of rapamycin pre‐ and posttreatment was tested on kainate‐induced dendritic injury and cofilin‐mediated actin depolymerization. Results Kainate‐induced seizures caused acute activation of mTORC 1 activity, which was prevented by the mTORC 1 inhibitor, rapamycin. Rapamycin pretreatment, and to a lesser degree, posttreatment attenuated acute seizure‐induced dendritic injury and correspondingly decreased LIM kinase and cofilin‐mediated depolymerization of actin. Interpretation The mTORC 1 pathway mediates seizure‐induced dendritic injury via depolymerization of actin. These findings have important mechanistic and translational applications for management of seizure‐induced brain injury.