sb-242084 and Chromosome-Deletion

In Prader-Willi syndrome (PWS), nonprotein coding small nucleolar (sno) RNAs are involved in the paternally deleted region of chromosome 15q11.2-q13, which is believed to cause the hyperphagic phenotype of PWS. Central to this is SnoRNA116. The supplement Caralluma fimbriata extract (CFE) has been shown to decrease appetite behavior in some individuals with PWS. We therefore investigated the mechanism underpinning the effect of CFE on food intake in the Snord116del mouse. Experiments utilized appetite stimulants which included a 5-hydroxytryptamine (5-HT) 2c receptor antagonist (SB242084), as the 5-HT2cR is implicated in central signaling of satiety.. Caralluma fimbriata extract administration decreased food intake more strongly in the SNO100CFE group with significantly stimulated food intake demonstrated during coadministration with SB242084. Though stimulatory deprivation was expected to stimulate food intake, 2DG and MA resulted in lower intake in the snord116del mice compared to the WT animals (p = <0.001). Immunohistochemical mapping of hypothalamic neural activity was consistent with the behavioral studies.. This study identifies a role for the 5-HT2cR in CFE-induced appetite suppression and significant stimulatory feeding disruptions in the snord116del mouse model.

Topics: Aminopyridines; Animals; Apocynaceae; Appetite Depressants; Chromosome Deletion; Disease Models, Animal; Eating; Female; Gene Deletion; Humans; Hypothalamus; Indoles; Male; Mice, Inbred C57BL; Phenotype; Phytotherapy; Plant Extracts; Prader-Willi Syndrome; Random Allocation; Receptor, Serotonin, 5-HT2C; RNA, Small Nucleolar; Serotonin 5-HT2 Receptor Antagonists