title: The inhibition of transforming growth factor beta-activated kinase 1 contributed to neuroprotection via inflammatory reaction in pilocarpine-induced rats with epilepsy.
abstract: Recently, more and more studies support that inflammation is involved in the pathogenesis of epilepsy. Although TGFβ signaling is involved in epileptogenesis, whether TGFβ-associated neuroinflammation is sufficient to regulate epilepsy remains unknown to date. Furthermore, tumor necrosis factor-α receptor-associated factor-6 (TRAF6), transforming growth factor beta-activated kinase 1 (TAK1), which are the key elements of TGFβ-associated inflammation, is still unclear in epilepsy. Therefore, the present study aimed to explore the role of TRAF6 and TAK1 in pilocarpine-induced epileptic rat model. Firstly, the gene levels and protein expression of TRAF6 and TAK1 were detected in different time points after pilocarpine-induced status epilepticus (SE). 5z-7-oxozeaenol treatment (TAK1 antagonist) was then performed; the changes in TRAF6, TAK1, phosphorylated-TAK1 (P-TAK1), interleukin-1β (IL-1β) levels, neuronal survival and apoptosis, and seizure activity were detected. Our results showed that expressions of TRAF6 were increased after SE, reached the peak in 7day, maintained at the high level to 30days, and the TAK1, P-TAK1 levels were increased after SE following time. After 5z-7-oxozeaenol treatment in epileptic rats, TRAF6-TAK1-P-TAK1 signaling protein expressions were reduced, inflammatory cytokine IL-1β expression was decreased, neuron survival index was improved, the neuron apoptosis index was decreased and seizure durations were alleviated. In conclusion, the expression of TRAF6 and TAK1 are related to the progression of epilepsy. TAK1 might be a potential intervention target for the treatment of epilepsy via neuroprotection.
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: M
authors.initials: M
authors.lastname: Gu
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
authors.forename: N
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: lyu_yang@126.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Lü
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D000066829:Neuroprotection; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000150:complications / Q000378:metabolism*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D015025:Zearalenone / Q000008:administration & dosage / Q000031:analogs & derivatives; D000099151:MAP Kinase Kinase Kinase 7; D007783:Lactones; D012118:Resorcinols
chemical_list: D053583:Interleukin-1beta; D020930:MAP Kinase Kinase Kinases; D010862:Pilocarpine; D048029:TNF Receptor-Associated Factor 6; D015025:Zearalenone; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols
keywords: TAK1; TRAF6; epilepsy; neuroprotection; seizure