Neural progenitor cells Rptor Ablation impairs development but benefits to postepileptic behaviors
Abstract number :
1.005
Submission category :
1. Translational Research: 1A. Mechanisms / 1A1. Epileptogenesis of acquired epilepsies
Year :
2016
Submission ID :
190414
Source :
www.aesnet.org
Presentation date :
12/3/2016 12:00:00 AM
Published date :
Nov 21, 2016, 18:00 PM
Authors :
Linglin Chen, Zhejiang University City college; Meiling Wu, Zhejiang University City college; Jiejing Kai, Zhejiang University City COllege; and Linghui Zeng, Zhejiang University City college
Rationale: Previous study suggests that mTOR signaling pathway may play an important role in epileptogenesis. The present work was designed to explore the contribution of raptor protein to the development of epilepsy and comorbidity. Methods: Mice with conditional knockout of raptor protein were generated by cross-bred Rptorflox/flox mice with nestin-CRE mice. The mTOR signaling pathway of Rptor CKO mice in naﶥ or after epileptic status were analysis by western blotting. Neuronal death and mossy fiber sprouting were detected by FJB staining and Timm staining, respectively. Spontaneous seizures were recorded by EEG-video. Morris water maze, open field test, and excitability test were used to study the behaviors of Rptor CKO mice. Results: As the consequence of deleting Rptor, downstream proteins of raptor in mTORC1 signaling were partly blocked. Rptor CKO mice exhibited decrease in body and brain weight under 7 weeks old of age and accordingly. After kainic acid (KA)-induced status epilepticus, over-activation of mTORC1 signaling was markedly reversed in Rptor CKO mice. Though low frequency of spontaneous seizure and seldom neuronal cell death were observed in both Rptor CKO and control littermates, KA-seizure induced mossy fiber spouting were attenuated in Rptor CKO mice. Additionally, cognitive deficit and anxiety-like behavior after KA-induced seizure were improved in Rptor CKO mice. Conclusions: Loss of the rptor gene in mice neural progenitor cells affects normal development in young age and may contribute to alleviate epileptic behavioral abnormality, suggesting that raptor protein plays an important role in epilepsy. Funding: This work was supported by National Natural Science Foundation of China (81371429 to L. Z.), Department of Science and Technology of Zhejiang Province, Project of Experiment Animal Platform(2013C37026 to L.Z.)
Translational Research