title: Brain-derived neurotrophic factor, corticotropin-releasing factor, and hypothalamic neuronal histamine interact to regulate feeding behavior.
abstract: Brain-derived neurotrophic factor (BDNF), corticotropin-releasing factor (CRF), and hypothalamic neuronal histamine are anorexigenic substances within the hypothalamus. This study examined the interactions among BDNF, CRF, and histamine during the regulation of feeding behavior in rodents. Food intake was measured after treatment with BDNF, α-fluoromethyl histidine (FMH; a specific suicide inhibitor of histidine decarboxylase that depletes hypothalamic neuronal histamine), or CRF antagonist. We measured food intake in wild-type mice and mice with targeted disruption of the histamine H1 receptor (H1KO mice) after central BDNF infusion. Furthermore, we investigated CRF content and histamine turnover in the hypothalamus after BDNF treatment, and conversely, BDNF content in the hypothalamus after histamine treatment. We used immunohistochemical staining for histamine H1 receptors (H1-R) in BDNF neurons. BDNF-induced feeding suppression was partially attenuated in rats pre-treated with FMH or a CRF antagonist, and in H1KO mice. BDNF treatment increased CRF content and histamine turnover in the hypothalamus. Histamine increased BDNF content in the hypothalamus. Immunohistochemical analysis revealed that H1-Rs were expressed on BDNF neurons in the ventromedial nucleus of the hypothalamus. These results indicate that CRF and hypothalamic neuronal histamine mediate the suppressive effects of BDNF on feeding behavior and body weight.
authors: Department of Internal Medicine 1, Faculty of Medicine, Oita University, Yufu, Japan. gotokoro@oita-u.ac.jp
authors: Koro
authors: K
authors: Gotoh
authors: Takayuki
authors: T
authors: Masaki
authors: Seiichi
authors: S
authors: Chiba
authors: Hisae
authors: H
authors: Ando
authors: Kansuke
authors: K
authors: Fujiwara
authors: Takanobu
authors: T
authors: Shimasaki
authors: Kimihiko
authors: K
authors: Mitsutomi
authors: Isao
authors: I
authors: Katsuragi
authors: Tetsuya
authors: T
authors: Kakuma
authors: Toshiie
authors: T
authors: Sakata
authors: Hironobu
authors: H
authors: Yoshimatsu
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011969:Receptors, Histamine H1; D006632:Histamine; D003346:Corticotropin-Releasing Hormone