FP30-3 Effects of Gold Thioglucose Treatment on Central Corticotropin-Releasing Hormone Systems in Mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP30-Central Regulation of Appetite & Feeding
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:55 AM
Room 304 (Moscone Center)

Poster Board MON-675
Shinya Makino*1, Tohru Noguchi2, Mitsuru Nishiyama3, Kozo Hashimoto4 and Yoshio Terada5
1Osaka Gyomeikan Hosp, Osaka, Japan, 2Kochi Med Schl, Nankoku, Japan, 3Kochi Medical Sch, Kochi, Japan, 4Hosogi Hospital, Kochi, Japan, 5Kochi Medical School, Nankoku, Japan
Systemic administration of gold thioglucose (GTG) causes a hypothalamic lesion that extends from the ventral part of the ventromedial hypothalamus (VMH) to the dorsal part of the arcuate nucleus (ARC), resulting in hyperphagia and obesity in mice. Therefore, we used in situ hybridization histochemistry to explore the effects of GTG on the central corticotropin-releasing hormone (CRH) system, which regulates feeding and energy homeostasis. Type 2 CRH receptor (CRHR-2) mRNA expression decreased by 40% at 8 weeks in the VMH and by 40-60% at 2 and 8 weeks in the ARC after GTG injection. In contrast, CRHR-2 mRNA expression in the hypothalamic paraventricular nucleus (PVN) and lateral septum was unchanged. Urocortin 3 (Ucn 3) mRNA expression in the perifornical area and medial amygdala decreased, whereas CRH mRNA expression in the PVN increased at 2 and 8 weeks after GTG injection. Ucn 1 mRNA expression in the Edingher-Westphal nucleus and Ucn 2 mRNA expression in the PVN were unchanged. Because Ucn 3 is an anorexigenic and a possible endogenous ligand for VMH CRHR-2, our results suggest that decreased Ucn 3 expression and decreased VMH CRHR-2 expression contribute, in part, to GTG-induced hyperphagia and obesity. To determine whether VMH CRHR-2 mediates the anorexigenic effects of Ucn 3, Ucn 3 was administered intracerebroventricularly and food intake was measured 8 weeks after GTG treatment. Ucn 3 decreased cumulative food intake on days 4-7 after surgery, as compared with intracerebroventricular administration of vehicle in control mice. By contrast, the anorexigenic effects of intracerebroventricular Ucn 3 were abolished in GTG-treated mice. Taken together, our results indicate that the Ucn 3 pathway, which innervates the VMH, is involved in appetite regulation via CRHR-2. It remains to be determined whether CRHR-2 in the ARC has additional roles in appetite regulation by Ucn 3.

Nothing to Disclose: SM, TN, MN, KH, YT

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