title: Effects of JIP3 on epileptic seizures: Evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures.
abstract: JNK-interacting protein 3 (JIP3), also known as JNK stress-activated protein kinase-associated protein 1 (JSAP1), is a scaffold protein mainly involved in the regulation of the pro-apoptotic signaling cascade mediated by c-Jun N-terminal kinase (JNK). Overexpression of JIP3 in neurons in vitro has been reported to lead to accelerated activation of JNK and enhanced apoptosis response to cellular stress. However, the occurrence and the functional significance of stress-induced modulations of JIP3 levels in vivo remain elusive. In this study, we investigated the expression of JIP3 in temporal lobe epilepsy (TLE) and in a kainic acid (KA)-induced mouse model of epileptic seizures, and determined whether down-regulation of JIP3 can decrease susceptibility to seizures and neuron damage induced by KA. We found that JIP3 was markedly increased in TLE patients and a mouse model of epileptic seizures; mice underexpressing JIP3 through lentivirus bearing LV-Letm1-RNAi showed decreased susceptibility, delayed first seizure and decreased seizure duration response to the epileptogenic properties of KA. Subsequently, a decreased activation of JNK following seizure induction was observed in mice underexpressing JIP3, which also exhibited less neuronal apoptosis in the CA3 region of the hippocampus, as assessed three days after KA administration. We also found that mice underexpressing JIP3 exhibited a delayed pentylenetetrazole (PTZ)-induced kindling seizure process.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China; Department of Neurology, Fuling Central Hospital, Chongqing 408000, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lü
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: X
authors.initials: X
authors.lastname: Mi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: W
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China. Electronic address: xfyp@163.com.
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D056654:CA3 Region, Hippocampal / Q000201:enzymology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007608:Kainic Acid; D007696:Kindling, Neurologic / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D010433:Pentylenetetrazole; D034622:RNA Interference; D012640:Seizures / Q000201:enzymology* / Q000473:pathology; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485750:MAPK8IP3 protein, human; C403619:Mapk8ip3 protein, mouse; D009419:Nerve Tissue Proteins; D007608:Kainic Acid; D010433:Pentylenetetrazole
keywords: JIP3; JNK; apoptosis; lentivirus; temporal lobe epilepsy