title: Tissue plasminogen activator modulates emotion in a social context.
abstract: Tissue plasminogen activator (tPA) is known to play physiologically and pathologically crucial roles in the central nervous system. However, it is still obscure whether it affects social behavior. We investigated social behavior and neuronal activation after social stimulation in tPA knockout (KO) mice. In a resident-intruder test, the latency to the first contact was significantly delayed in tPA KO mice compared with that in tPA heterogenic (Het) mice. However, tPA KO mice spent significantly more time undertaking active behavior than tPA Het mice did. In a sociability test, tPA KO mice significantly spent more time and walked a greater distance in the chamber containing an empty cage than tPA Het mice. Furthermore, tPA KO mice approached an empty cage more frequently than tPA Het mice did. In a social novelty test, there was no difference in the duration spent sniffing a stimulator mouse between genotypes. However, tPA KO mice approached even a familiar mouse more frequently than tPA Het mice did. tPA KO mice spent similar durations in a chamber containing a familiar mouse and that containing an unfamiliar mouse, and tPA KO mice walked a significantly greater distance in the former chamber than tPA Het mice did. Furthermore, at the cingulate and prelimbic cortices, the number of cFos-positive cells was significantly increased in tPA KO mice compared with that in tPA Het mice after social stimulation. Our results suggest that tPA modulates emotion in a social context through the function of the prefrontal cortex.
authors.affiliation: Department of Occupational Therapy, Gunma University, Showa 3-39-22, Maebashi 371-8514, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Occupational Therapy, Gunma University, Showa 3-39-22, Maebashi 371-8514, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Takabe
authors.affiliation: Department of Occupational Therapy, Gunma University, Showa 3-39-22, Maebashi 371-8514, Japan.
authors.forename: Fuki
authors.initials: F
authors.lastname: Shimizu
authors.affiliation: Department of Occupational Therapy, Gunma University, Showa 3-39-22, Maebashi 371-8514, Japan; Department of Rehabilitation Sciences, Gunma University School of Health Sciences, Showa 3-39-22, Maebashi 371-8514, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Kinki University Faculty of Medicine, Osakasayama 589-8511, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
authors.affiliation: Department of Occupational Therapy, Gunma University, Showa 3-39-22, Maebashi 371-8514, Japan; Department of Rehabilitation Sciences, Gunma University School of Health Sciences, Showa 3-39-22, Maebashi 371-8514, Japan. Electronic address: smitsui@gunma-u.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mitsui
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004644:Emotions / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D006179:Gyrus Cinguli / Q000378:metabolism; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012919:Social Behavior; D012931:Social Environment; D010959:Tissue Plasminogen Activator / Q000172:deficiency* / Q000235:genetics
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D010959:Tissue Plasminogen Activator
keywords: Autism; Interaction; Prefrontal cortex; Serine protease; Social behavior