Agouti‐related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice

• DOI: 10.1111/jne.13190
• Publication Date: 2022-07-31T09:09:45Z
• Authors: Caroline Decourt; George A. D. P. C...; Caroline Ancel; Megan A. Inglis; Greg M. Anderson
• Keywords: Orexigenic; Delayed puberty; Preputial gland

Agouti-related peptide (AgRP) neurons are thought to indirectly regulate the activity of hypothalamic gonadotrophin-releasing hormone which control fertility. AgRP also drive caloric intake and modulated by metabolically-relevant hormones, providing a link hypothalamic-pituitary-gonadal axis. In mice expressing Cre-dependant designer receptors (DREADDs) in neurons, we activated or silenced these vivo using synthetic ligand clozapine-N-oxide (CNO) observe effect neuron on timing puberty. To validate animals, chronically treated both stimulatory (hM3Dq) inhibitory (hM4Di) DREADD × AgRP-Cre with CNO, observing pronounced increase decrease food intake, respectively, consistent known orexigenic effects neurons. RNAscope was performed visually confirm activation Puberty onset assessed males females. There no preputial separation vaginal opening first oestrus females after CNO treatment from day 26 30 modulate Next, determine whether delay puberty occurring response neonatal underfeeding could be overcome inhibiting neuronal activity, were raised large (neonatally underfed) normal litter sizes. The completely reversed CNO-treated AgRP-hM4Di male mice. These data highlight role when undernutrition occurs during period, at least TRAIL REGISTRATION NUMBER: JNE-22-0081-OA.R2.