title: Role of the Oxytocin Receptor Expressed in the Rostral Medullary Raphe in Thermoregulation During Cold Conditions.
abstract: Recent papers have reported that oxytocin (Oxt) and the oxytocin receptor (Oxtr) may be involved in the regulation of food intake in mammals. We therefore suspected the Oxt/Oxtr system to be involved in energy homeostasis. In previous studies, we found a tendency toward obesity in Oxtr-deficient (Oxtr (-/-)) mice, as well as impaired thermoregulation when these mice were exposed to cold conditions. In the present study, we observed the expression of Oxtr in the rostral medullary raphe (RMR), the brain region known to control thermogenesis in brown adipose tissue (BAT). Through immunohistochemistry, we detected neurons expressing Oxtr and c-Fos in the RMR of mice exposed to cold conditions. Up to 40% of Oxtr-positive neurons in RMR were classified as glutamatergic neurons, as shown by immunostaining using anti-VGLUT3 antibody. In addition, mice with exclusive expression of Oxtr in the RMR were generated by injecting an AAV-Oxtr vector into the RMR region of Oxtr (-/-) mice. We confirmed the recovery of thermoregulatory ability in the manipulated mice during exposure to cold conditions. Moreover, mice with RMR-specific expression of Oxtr lost the typical morphological change in BAT observed in Oxtr (-/-) mice. Additionally, increased expression of the β3-adrenergic receptor gene, Adrb3, was observed in BAT. These results are the first to show the critical role of RMR Oxtr expression in thermoregulation during cold conditions.
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University , Miyagi , Japan ; Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University , Miyagi , Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kasahara
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University , Miyagi , Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tateishi
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University , Miyagi , Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hiraoka
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University , Miyagi , Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Otsuka
authors.affiliation: Division of Genetic Therapeutics, Centre for Molecular Medicine, Jichi Medical University , Tochigi , Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.affiliation: Division of Genetic Therapeutics, Centre for Molecular Medicine, Jichi Medical University , Tochigi , Japan.
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University , Miyagi , Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University , Miyagi , Japan.
authors.forename: Shizu
authors.initials: S
authors.lastname: Hidema
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University , Miyagi , Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nishimori
keywords: body thermoregulation; energy homeostasis; oxytocin; oxytocin receptor; rostral medullary raphe