title: Inhibition of the small GTPase Cdc42 in regulation of epileptic-seizure in rats.
abstract: Altered expression of neuronal cytoskeletal proteins are known to play an important role in hyper-excitability of neurons in patients and animal models of epilepsy. Our previous work showed that cell division cycle 42 GTP-binding protein (Cdc42), a small GTPase of the Rho-subfamily, is significantly increased in the brain tissue of patients with temporal lobe epilepsy (TLE) and in the brain tissues of the epileptic model of rats. However, whether inhibition of Cdc42 can modify epileptic seizures has not been investigated. In this study, using a pilocarpine-induced epileptic model, we found that pretreatment with ML141, a specific inhibitor of Cdc42, reduces seizure severity. Whole-cell patch-clamp recording on CA1 pyramidal neurons in hippocampal slices from pilocarpine-induced epileptic model demonstrated that ML141 significantly inhibits the frequency of action potentials (APs), increases the amplitude and frequency of miniature inhibitory postsynaptic currents (mIPSCs), and increases the amplitude of evoked inhibitory postsynaptic currents (eIPSCs). However, ML141 did not have an impact on the miniature excitatory postsynaptic currents (mEPSCs). Our results are the first to indicate that Cdc42 plays an important role in the onset and progression of epileptic-seizures by regulating synaptic inhibition.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, 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, 1 Youyi Road, Chongqing 400016, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center of Epilepsy, Beijing Institute for Brain Disorders, China.
authors.forename: G
authors.initials: G
authors.lastname: Luan
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China. Electronic address: xfyp@163.com.
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000201:enzymology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology; D008297:Male; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010862:Pilocarpine; D017966:Pyramidal Cells / Q000187:drug effects / Q000201:enzymology*; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000201:enzymology*; D013449:Sulfonamides / Q000494:pharmacology; D046509:Tissue Culture Techniques; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000096926:Benzenesulfonamides
chemical_list: D004791:Enzyme Inhibitors; D010862:Pilocarpine; D011720:Pyrazoles; D013449:Sulfonamides; D020764:cdc42 GTP-Binding Protein; C581055:CID2950007; D000096926:Benzenesulfonamides
keywords: Cdc42 (cell division cycle 42 GTP-binding protein); ML141; epilepsy; seizure; synaptic inhibition