title: Altered behavior and neural activity in conspecific cagemates co-housed with mouse models of brain disorders.
abstract: The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (>4weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong, Daejeon 305-701, South Korea.
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong, Daejeon 305-701, South 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, 291 Daehak-ro, Yuseong, Daejeon 305-701, South Korea.
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Seo
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong, Daejeon 305-701, South Korea.
authors.forename: Arshi
authors.initials: A
authors.lastname: Khalid
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea.
authors.forename: Jung-Seok
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea.
authors.forename: Soyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea.
authors.forename: Jangsup
authors.initials: J
authors.lastname: Moon
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea. Electronic address: stemcell.snu@gmail.com.
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea. Electronic address: sangkun2923@gmail.com.
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea; Advanced Neural Technologies, Seoul 03087, South Korea. Electronic address: clark.jeon@gmail.com.
authors.forename: Daejong
authors.initials: D
authors.lastname: Jeon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000503:physiopathology* / Q000523:psychology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D003863:Depression / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology*; D004597:Electroshock / Q000009:adverse effects; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology*; D005106:Exploratory Behavior / Q000502:physiology; D019417:Hindlimb Suspension; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000633:toxicity; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000633:toxicity; D013550:Swimming
chemical_list: D018721:Muscarinic Agonists; D010862:Pilocarpine
keywords: Behavior; Co-housing; Mouse; Prefrontal cortex; Psychosocial environment; Social stress