Neural Progenitor Cells Rptor Ablation Impairs Development but Benefits to Seizure-Induced Behavioral Abnormalities.
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 comorbidities.



Mice with conditional knockout of raptor protein were generated by cross-bred Rptorflox/floxmice with nestin-CRE mice. The expression of raptor protein was analyzed by Western blotting in brain tissue samples. Neuronal death and mossy fiber sprouting were detected by FJB staining and Timm staining, respectively. Spontaneous seizures were recorded by EEG-video system. Morris water maze, open field test, and excitability test were used to study the behaviors of Rptor CKO mice.



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 and accordingly, cortical layer thickness. After kainic acid (KA)-induced status epilepticus, overactivation of mTORC1 signaling was markedly reversed in Rptor CKO mice. Although 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 seizures were partly reversed in Rptor CKO mice.



Loss of the Rptor gene in mice neural progenitor cells affects normal development in young age and may contribute to alleviate KA seizure-induced behavioral abnormalities, suggesting that raptor protein plays an important role in seizure comorbidities.
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Ling-Lin
LL
Chen
Department of Pharmacy, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China.
Mei-Ling
ML
Wu
Department of Pharmacy, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China.
Feng
F
Zhu
Department of Pharmacy, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China.
Jie-Jing
JJ
Kai
Department of Pharmacy, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China.
Jing-Yin
JY
Dong
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Xi-Mei
XM
Wu
Department of Pharmacy, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China.
Ling-Hui
LH
Zeng
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000235:genetics; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D018782:Maze Learning / Q000502:physiology; D000076222:Mechanistic Target of Rapamycin Complex 1; D001523:Mental Disorders / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000378:metabolism; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000076223:Regulatory-Associated Protein of mTOR; D012097:Repressor Proteins / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000150:complications*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C000624101:Cux1 protein, mouse; D018690:Excitatory Amino Acid Agonists; D018398:Homeodomain Proteins; D046912:Multiprotein Complexes; D064231:Nestin; D009687:Nuclear Proteins; D000076223:Regulatory-Associated Protein of mTOR; D012097:Repressor Proteins; C540162:Rptor protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D007608:Kainic Acid
Behaviors; Epilepsy; Kainic acid; Rptor CKO mice; mTOR signaling pathway
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