title: Association of cathepsin E deficiency with the increased territorial aggressive response of mice.
abstract: Cathepsin E is an endolysosomal aspartic proteinase predominantly expressed in cells of the immune system, but physiological functions of this protein in the brain remains unclear. In this study, we investigate the behavioral effect of disrupting the gene encoding cathepsin E in mice. We found that the cathepsin E-deficient (CatE-/-) mice were behaviorally normal when housed communally, but they became more aggressive compared with the wild-type littermates when housed individually in a single cage. The increased aggressive response of CatE-/- mice was reduced to the level comparable to that seen for CatE+/+ mice by pretreatment with an NK-1-specific antagonist. Consistent with this, the neurotransmitter substance P (SP) level in affective brain areas including amygdala, hypothalamus, and periaqueductal gray was significantly increased in CatE-/- mice compared with CatE+/+ mice, indicating that the increased aggressive behavior of CatE-/- mice by isolation housing followed by territorial challenge is mainly because of the enhanced SP/NK-1 receptor signaling system. Double immunofluorescence microscopy also revealed the co-localization of SP with synaptophysin but not with microtubule-associated protein-2. Our data thus indicate that cathepsin E is associated with the SP/NK-1 receptor signaling system and thereby regulates the aggressive response of the animals to stressors such as territorial challenge.
authors.affiliation: Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Shigematsu
authors.forename: Takaichi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Tsuneyuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nishioku
authors.forename: Taku
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Masaru
authors.initials: M
authors.lastname: Himeno
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsukuba
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Okamoto
authors.forename: Shun
authors.initials: S
authors.lastname: Higuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000374:Aggression / Q000502:physiology* / Q000523:psychology; D000818:Animals; D020059:Cathepsin E / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology; D012934:Social Isolation / Q000523:psychology; D013731:Territoriality
chemical_list: D020059:Cathepsin E