title: Dual mechanisms of rapid expression of anxiety-related behavior in pilocarpine-treated epileptic mice.
abstract: A mouse model of epilepsy was generated by inducing status epilepticus (SE) for either 1.5 or 4.5h with pilocarpine to study anxiety-related behaviors, changes in the electroencephalogram of the cerebral cortex and hippocampus, and expression of hippocampal proteins. The viability and rate of success of SE induction were high in C57BL/6N mice but not in C57BL/6J mice. C57BL/6N mice were immotile during the first 2days after SE; however, by the third day, most mice were recovered and exhibited strong anxiety-related behaviors in response to the light/dark preference test and open field test. There was a striking difference in the temporal appearance of anxiety-related behavior between the two SE durations: 1.5h SE mice exhibited strong anxiety-related behavior 3days after SE that gradually attenuated over the next few weeks, whereas 4.5h SE mice exhibited strong anxiety-related behavior 3days after SE that persisted even at nearly 1year after SE. Mice receiving both SE durations exhibited generalized seizures (GS) after SE; however, there was a marked difference in the timing and duration of GS appearance. Mice in the 4.5h SE group exhibited spontaneous GS from 4days to at least 96days after SE. In contrast, mice in the 1.5h SE group exhibited GS only within the first several days after SE; however, epileptic spike clusters continuously appeared in the cerebral cortex and hippocampus for up to twelve days after SE. Among the hippocampal proteins tested, only brain derived-neurotrophic factor (BDNF) exhibited altered expression in parallel with anxiety-related behavior. These results showed the possibility that BDNF expression in the hippocampus might cause anxiety-related behavior in adulthood.
authors.affiliation: Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0374, Japan. Electronic address: otsuka.z6@keio.jp.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Otsuka
authors.affiliation: Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0374, Japan. Electronic address: hyakumankaiikitaneko8@gmail.com.
authors.forename: Taro
authors.initials: T
authors.lastname: Ohkido
authors.affiliation: Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0374, Japan. Electronic address: mitakura@med.kitasato-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Itakura
authors.affiliation: Department of Psychiatry, Kitasato University School of Medicine, 2-1-1 Asamizodai, Minami-ku, Sagamihara-shi, Kanagawa 252-0380, Japan. Electronic address: nabesige@kitasato-u.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0374, Japan. Electronic address: yamamori@med.kitasato-u.ac.jp.
authors.forename: Saori
authors.initials: S
authors.lastname: Yamamori
authors.affiliation: Department of Psychiatry, Kitasato University School of Medicine, 2-1-1 Asamizodai, Minami-ku, Sagamihara-shi, Kanagawa 252-0380, Japan. Electronic address: yuukirf4@fancy.ocn.ne.jp.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Iida
authors.affiliation: Department of Psychiatry, Kitasato University School of Medicine, 2-1-1 Asamizodai, Minami-ku, Sagamihara-shi, Kanagawa 252-0380, Japan. Electronic address: 7n2ecx@mtf.biglobe.ne.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Psychiatry, Kitasato University School of Medicine, 2-1-1 Asamizodai, Minami-ku, Sagamihara-shi, Kanagawa 252-0380, Japan. Electronic address: miyaoka@med.kitasato-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyaoka
authors.affiliation: Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0374, Japan; Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0374, Japan. Electronic address: masami@med.kitasato-u.ac.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000378:metabolism*; D000067289:Behavior Observation Techniques; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D004569:Electroencephalography; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010862:Pilocarpine / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000523:psychology*; D013997:Time Factors
chemical_list: D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D017470:Receptors, Glutamate; C528900:glial fibrillary astrocytic protein, mouse; D010862:Pilocarpine
keywords: Anxiety-like behavior; BDNF; Brain-derived neurotrophic factor; Electroencephalogram; Epilepsy; Pilocarpine