MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process
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 imp...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2016/5108489 |
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| author | Jinxian Yuan Hao Huang Xin Zhou Xi Liu Shu Ou Tao Xu Ruohan Li Limin Ma Yangmei Chen |
| author_facet | Jinxian Yuan Hao Huang Xin Zhou Xi Liu Shu Ou Tao Xu Ruohan Li Limin Ma Yangmei Chen |
| author_sort | Jinxian Yuan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4aa05605722e4d40b34f2f989f3aa16e |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-4aa05605722e4d40b34f2f989f3aa16e2025-02-03T05:46:33ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/51084895108489MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis ProcessJinxian Yuan0Hao Huang1Xin Zhou2Xi Liu3Shu Ou4Tao Xu5Ruohan Li6Limin Ma7Yangmei Chen8Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaIncreasing 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.http://dx.doi.org/10.1155/2016/5108489 |
| spellingShingle | Jinxian Yuan Hao Huang Xin Zhou Xi Liu Shu Ou Tao Xu Ruohan Li Limin Ma Yangmei Chen MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process Neural Plasticity |
| title | MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process |
| title_full | MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process |
| title_fullStr | MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process |
| title_full_unstemmed | MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process |
| title_short | MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process |
| title_sort | microrna 132 interact with p250gap cdc42 pathway in the hippocampal neuronal culture model of acquired epilepsy and associated with epileptogenesis process |
| url | http://dx.doi.org/10.1155/2016/5108489 |
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