Stressor-responsive central nesfatin-1 activates corticotropin-releasing hormone, noradrenaline and serotonin neurons and evokes hypothalamic-pituitary-adrenal axis.
A recently discovered satiety molecule, nesfatin-1, is localized in neurons of the hypothalamus and brain stem and colocalized with stress-related substances, corticotropin-releasing hormone (CRH), oxytocin, proopiomelanocortin, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). Intracerebroventricular (icv) administration of nesfatin-1 produces fear-related behaviors and potentiates stressor-induced increases in plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in rats. These findings suggest a link between nesfatin-1 and stress. In the present study, we aimed to further clarify the neuronal network by which nesfatin-1 could induce stress responses in rats. Restraint stress induced c-Fos expressions in nesfatin-1-immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus, and in the nucleus of solitary tract (NTS), locus coeruleus (LC) and dorsal raphe nucleus (DR) in the brain stem, without altering plasma nesfatin-1 levels. Icv nesfatin-1 induced c-Fos expressions in the PVN, SON, NTS, LC, DR and median raphe nucleus, including PVN-CRH, NTS-NA, LC-NA and DR-5-HT neurons. Nesfatin-1 increased cytosolic Ca2+ concentration in the CRH-immunoreactive neurons isolated from PVN. Icv nesfatin-1 increased plasma ACTH and corticosterone levels. These results indicate that the central nesfatin-1 system is stimulated by stress and activates CRH, NA and 5-HT neurons and hypothalamic-pituitary-adrenal axis, evoking both central and peripheral stress responses.
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
Natsu
N
Yoshida
Yuko
Y
Maejima
Udval
U
Sedbazar
Akihiko
A
Ando
Hideharu
H
Kurita
Boldbaatar
B
Damdindorj
Eisuke
E
Takano
Darambazar
D
Gantulga
Yusaku
Y
Iwasaki
Tomoyuki
T
Kurashina
Tatsushi
T
Onaka
Katsuya
K
Dezaki
Masanori
M
Nakata
Masatomo
M
Mori
Toshihiko
T
Yada
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004268:DNA-Binding Proteins; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008125:Locus Coeruleus / Q000166:cytology / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000097:blood / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D000080866:Nucleobindins; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism; D051381:Rats; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism*; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism; D013312:Stress, Physiological; D013315:Stress, Psychological; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D012701:Serotonin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D002118:Calcium; D003345:Corticosterone; D009638:Norepinephrine