title: Heightened aggressive behavior in mice deficient in aldo-keto reductase 1a (Akr1a).
abstract: Aldehyde reductase (Akr1a) is involved in the synthesis of ascorbic acid (AsA) which may play a role in social behavior. In the current study, we performed analyses on Akr1a-deficient (Akr1a-/-) mice that synthesize about 10% as much AsA as wild-type mice from the viewpoint of intermale aggression. The use of the resident-intruder test revealed that the Akr1a-/-mice exhibited more aggressive phenotypes than wild-type control mice. Unexpectedly, however, the oral administration of additional AsA failed to reduce the aggressive behavior of Akr1a-/-mice, suggesting that the heightened aggression was independent of AsA biosynthesis. The findings also show that the plasma levels of corticosterone, but not serotonin and testosterone, were increased in the absence of Akr1a in mice, suggesting that the mice were highly stressed. These results suggest that Akr1a might be involved in the metabolism of steroids and other carbonyl-containing compounds and, hence, the absence of Akr1a results in heightened aggression via a malfunction in a metabolic pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Takujiro
authors.initials: T
authors.lastname: Homma
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Akihara
authors.affiliation: Research Laboratory for Molecular Genetics, Yamagata University School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okano
authors.affiliation: Health Research Institute (HRI), National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan.
authors.forename: Mototada
authors.initials: M
authors.lastname: Shichiri
authors.affiliation: Health Research Institute (HRI), National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Bio-functional Science, Faculty of Pharmacological Science, Kyushu University, Fukuoka, Japan; JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Yamada
authors.affiliation: Department of Internal Medicine, Osaka Hospital, Japan Community Healthcare Organization, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Research Laboratory for Molecular Genetics, Yamagata University School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakajima
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan. Electronic address: jfujii@med.id.yamagata-u.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects; D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000074408:Aldo-Keto Reductases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012420:Running / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002395:Catecholamines; D012701:Serotonin; D013739:Testosterone; D000074408:Aldo-Keto Reductases; D001205:Ascorbic Acid; D003345:Corticosterone
keywords: Akr1a; Ascorbic acid; Intermale aggression; Stress