title: Social deficits in the AY-9944 mouse model of atypical absence epilepsy.
abstract: Atypical absence epilepsy (AAE) showing slow spike-and-wave discharges (SWD) is characterized by severely abnormal cognition and neurodevelopmental or neurological outcomes in humans. However, despite the severe behavioral outcomes in AAE, the relationship between AAE and social-behavioral dysfunctions has not defined well, either experimentally or in patients with AAE. Experimentally, AAE can be produced by administering AY-9944 (AY), a cholesterol biosynthesis inhibitor. In this study, we characterized social behavior in the AY mouse model of AAE. AAE in the mouse was induced by repeated postnatal administration of AY every 6 days from postnatal day (P) 2 to P20. AY-treated mice exhibited spontaneous, recurrent, and synchronous SWD (4-5 Hz) in electroencephalographic recordings. AY-treated mice performed tasks involving sociability/social novelty preference, social interaction with a juvenile conspecific, observational fear, and resident-intruder aggression. They showed behavioral dysfunction in social interactions with a juvenile conspecific and sociability/social novelty preference tasks. They also exhibited reduced social fear learning in observational fear conditioning. Interestingly, they showed increased levels of offensive behaviors in a resident-intruder task. However, AY-treated mice displayed normal levels of anxiety in light/dark transition and the elevated plus maze tasks, and showed slightly increased locomotor activity in an open-field task. These results demonstrate social dysfunction in the AY-induced AAE model. Our study of social behavior can also provide valuable information about Lennox-Gastaut syndrome, in which AAE is a component. Thus, our findings may help to understand behavioral pathogenesis or characteristics of patients with AAE.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea.
authors.forename: Seungmoon
authors.initials: S
authors.lastname: Jung
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea.
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Seo
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea.
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea.
authors.forename: Doheon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, 110-744, Republic of Korea.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, 110-744, Republic of Korea; Department of Premedicine, College of Medicine, Seoul National University, Seoul, 110-744, Republic of Korea.
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, 110-744, Republic of Korea.
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea. Electronic address: clark@kaist.ac.kr.
authors.forename: Daejong
authors.initials: D
authors.lastname: Jeon
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D004832:Epilepsy, Absence / Q000139:chemically induced* / Q000523:psychology*; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000523:psychology; D007398:Interpersonal Relations; D007858:Learning / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012903:Smell / Q000187:drug effects; D012919:Social Behavior; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride
chemical_list: D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride