title: MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process.
abstract: Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (miR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether miR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model. Silencing miR-132 inhibited the electrical excitability level of cultured epileptic neurons, whereas silencing p250GAP had an opposite effect. In addition, we verified the effect of miR-132 in vivo and found that silencing miR-132 inhibited the aberrant formation of dendritic spines and chronic spontaneous seizure in a lithium-pilocarpine-induced epileptic mouse model. Finally, we confirmed that silencing miR-132 has a neuroprotective effect on cultured epileptic neurons; however, this effect did not occur through the p250GAP pathway. Generally, silencing miR-132 may suppress spontaneous seizure activity through the miR-132/p250GAP/Cdc42 pathway by regulating the morphology and electrophysiology of dendritic spines; therefore, miR-132 may serve as a potential target for the development of antiepileptic drugs.
authors: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Jinxian
authors: 0000-0001-7600-8285
authors: J
authors: Yuan
authors: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Hao
authors: H
authors: Huang
authors: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Xin
authors: X
authors: Zhou
authors: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Xi
authors: X
authors: Liu
authors: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Shu
authors: 0000-0002-7018-9588
authors: S
authors: Ou
authors: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Tao
authors: T
authors: Xu
authors: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Ruohan
authors: 0000-0001-5576-4508
authors: R
authors: Li
authors: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Limin
authors: L
authors: Ma
authors: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors: Yangmei
authors: 0000-0002-9280-0851
authors: Y
authors: Chen
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D004827:Epilepsy / Q000378:metabolism* / Q000517:prevention & control; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C470196:ARHGAP32 protein, human; D000070416:Antagomirs; C581598:Cdc42 protein, mouse; D020690:GTPase-Activating Proteins; C546976:MIRN132 microRNA, mouse; D035683:MicroRNAs; D020764:cdc42 GTP-Binding Protein