title: Rapamycin prevents acute dendritic injury following seizures.
abstract: 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 (mTORC1) 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 mTORC1 activity, which was prevented by the mTORC1 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.
  
  
  CONCLUSIONS
  The mTORC1 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.
authors.affiliation: Department of Neurology and the Hope Center for Neurological Disorders Washington University School of Medicine St. Louis Missouri 63110.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Pharmacy School of Medicine Zhejiang University City College Hangzhou Zhejiang 310015 China.
authors.forename: Linghui
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Neurology and the Hope Center for Neurological Disorders Washington University School of Medicine St. Louis Missouri 63110.
authors.forename: Jia
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Pharmacy School of Medicine Zhejiang University City College Hangzhou Zhejiang 310015 China.
authors.forename: Linglin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology and the Hope Center for Neurological Disorders Washington University School of Medicine St. Louis Missouri 63110.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Rensing
authors.affiliation: Department of Neurology and the Hope Center for Neurological Disorders Washington University School of Medicine St. Louis Missouri 63110.
authors.forename: Michael
authors.initials: M
authors.lastname: Wong