title: A reduced susceptibility to chemoconvulsant stimulation in adenylyl cyclase 8 knockout mice.
abstract: OBJECTIVE
  Adenylyl cyclases (ACs) catalyze the synthesis of cAMP from ATP, and cAMP signaling affects a large number of neuronal processes. Ca(2+)-stimulated adenylyl cyclase 8 (AC8) expressed in the CNS plays a role in synaptic plasticity, drug addiction and ethanol sensitivity, and chronic pain. This study was to aim at examining the contributions of AC8 to epileptogenesis.
  
  
  METHODS
  In this study, we observed the seizure behavior induced by kainic acid (20 mg/kg or 30 mg/kg) or pilocarpine (350 mg/kg) in AC8 KO and wild-type mice. Next we injected kainic acid or pilocarpine to induce status epilepticus (SE), and examined neuronal degeneration (by Fluoro-Jade B staining) and mossy fiber sprouting (by Timm staining) 24h and 2 weeks after SE termination in the hippocampus, respectively. Finally, 15 min after intraperitoneal injection of kainic acid (30 mg/kg), we examined phosphor-ERK1/2 in the hippocampus by Western blot and immunochemistry staining.
  
  
  RESULTS
  We first observed that AC8 KO mutants display reduced susceptibility (including seizure latency and episodes) to two chemoconvulsants, kainic acid and pilocarpine. Moreover, we found that degenerative neurons and mossy fiber sprouting induced by chemoconvulsants were significant decreased in the hippocampus. Further, Western blot and immunochemistry analysis revealed that the MAPK signaling in the hippocampus was attenuated in kainic acid-injected AC8 KO mice.
  
  
  CONCLUSIONS
  AC8 is involved in epileptogenesis, and may serve as a potential target for the treatment of epilepsy.
authors.affiliation: Laboratory of Neurological Diseases, Department of Neurology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213003, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Neurological Diseases, Department of Neurology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213003, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Dong
authors.affiliation: Laboratory of Neurological Diseases, Department of Neurology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213003, China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Physiology and Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Neurological Diseases, Department of Neurology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213003, China. Electronic address: wenwei_yun@yahoo.com.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Yun
authors.affiliation: Laboratory of Neurological Diseases, Department of Neurology, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213003, China. Electronic address: xianju_zhou@yahoo.com.
authors.forename: Xianju
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000262:Adenylyl Cyclases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D010862:Pilocarpine / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D013226:Status Epilepticus / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D003292:Convulsants; D010862:Pilocarpine; D000262:Adenylyl Cyclases; C118292:adenylyl cyclase 8; D007608:Kainic Acid
keywords: AC8 knockout; Adenylyl cyclase; Calcium; Epilepsy; cAMP