Cargando…

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

Agouti‐related peptide (AgRP) neurons are thought to indirectly regulate the activity of hypothalamic gonadotrophin‐releasing hormone neurons which control fertility. AgRP neurons also drive caloric intake and are modulated by metabolically‐relevant hormones, providing a link to the hypothalamic–pit...

Descripción completa

Detalles Bibliográficos
Autores principales: Decourt, Caroline, Connolly, George A. D. P., Ancel, Caroline, Inglis, Megan A., Anderson, Greg M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788270/
https://www.ncbi.nlm.nih.gov/pubmed/36306199
http://dx.doi.org/10.1111/jne.13190
_version_ 1784858713492815872
author Decourt, Caroline
Connolly, George A. D. P.
Ancel, Caroline
Inglis, Megan A.
Anderson, Greg M.
author_facet Decourt, Caroline
Connolly, George A. D. P.
Ancel, Caroline
Inglis, Megan A.
Anderson, Greg M.
author_sort Decourt, Caroline
collection PubMed
description Agouti‐related peptide (AgRP) neurons are thought to indirectly regulate the activity of hypothalamic gonadotrophin‐releasing hormone neurons which control fertility. AgRP neurons also drive caloric intake and are modulated by metabolically‐relevant hormones, providing a link to the hypothalamic–pituitary‐gonadal axis. In mice expressing Cre‐dependant designer receptors (DREADDs) in AgRP neurons, we activated or silenced these neurons in vivo using the synthetic ligand clozapine‐N‐oxide (CNO) to observe the effect of AgRP neuron activity on timing of puberty. To validate these animals, we chronically treated both stimulatory (hM3Dq) and inhibitory (hM4Di) DREADD × AgRP‐Cre mice with CNO, observing a pronounced increase and decrease of food intake, respectively, consistent with the known orexigenic effects of these neurons. RNAscope was performed to visually confirm the activation of AgRP neurons. Puberty onset was assessed in males and females. There was no effect on preputial separation in males or vaginal opening and first oestrus in females after CNO treatment from day 26 to 30 to chronically modulate AgRP neurons. Next, to determine whether the delay in puberty onset occurring in response to neonatal underfeeding could be overcome by inhibiting AgRP neuronal activity, mice were raised in large (neonatally underfed) or normal litter sizes. The delay in puberty from underfeeding was completely reversed in CNO‐treated AgRP‐hM4Di male mice. These data highlight the inhibitory role of AgRP neurons to delay puberty onset when undernutrition occurs during the neonatal period, at least in male mice. TRAIL REGISTRATION NUMBER: JNE‐22‐0081‐OA.R2
format Online
Article
Text
id pubmed-9788270
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-97882702022-12-28 Agouti‐related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice Decourt, Caroline Connolly, George A. D. P. Ancel, Caroline Inglis, Megan A. Anderson, Greg M. J Neuroendocrinol Fundamental and Mechanistic Neuroendocrinology Agouti‐related peptide (AgRP) neurons are thought to indirectly regulate the activity of hypothalamic gonadotrophin‐releasing hormone neurons which control fertility. AgRP neurons also drive caloric intake and are modulated by metabolically‐relevant hormones, providing a link to the hypothalamic–pituitary‐gonadal axis. In mice expressing Cre‐dependant designer receptors (DREADDs) in AgRP neurons, we activated or silenced these neurons in vivo using the synthetic ligand clozapine‐N‐oxide (CNO) to observe the effect of AgRP neuron activity on timing of puberty. To validate these animals, we chronically treated both stimulatory (hM3Dq) and inhibitory (hM4Di) DREADD × AgRP‐Cre mice with CNO, observing a pronounced increase and decrease of food intake, respectively, consistent with the known orexigenic effects of these neurons. RNAscope was performed to visually confirm the activation of AgRP neurons. Puberty onset was assessed in males and females. There was no effect on preputial separation in males or vaginal opening and first oestrus in females after CNO treatment from day 26 to 30 to chronically modulate AgRP neurons. Next, to determine whether the delay in puberty onset occurring in response to neonatal underfeeding could be overcome by inhibiting AgRP neuronal activity, mice were raised in large (neonatally underfed) or normal litter sizes. The delay in puberty from underfeeding was completely reversed in CNO‐treated AgRP‐hM4Di male mice. These data highlight the inhibitory role of AgRP neurons to delay puberty onset when undernutrition occurs during the neonatal period, at least in male mice. TRAIL REGISTRATION NUMBER: JNE‐22‐0081‐OA.R2 John Wiley and Sons Inc. 2022-08-19 2022-10 /pmc/articles/PMC9788270/ /pubmed/36306199 http://dx.doi.org/10.1111/jne.13190 Text en © 2022 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Fundamental and Mechanistic Neuroendocrinology
Decourt, Caroline
Connolly, George A. D. P.
Ancel, Caroline
Inglis, Megan A.
Anderson, Greg M.
Agouti‐related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice
title Agouti‐related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice
title_full Agouti‐related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice
title_fullStr Agouti‐related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice
title_full_unstemmed Agouti‐related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice
title_short Agouti‐related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice
title_sort agouti‐related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice
topic Fundamental and Mechanistic Neuroendocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788270/
https://www.ncbi.nlm.nih.gov/pubmed/36306199
http://dx.doi.org/10.1111/jne.13190
work_keys_str_mv AT decourtcaroline agoutirelatedpeptideneuronalsilencingovercomesdelayedpubertyinneonatallyunderfedmalemice
AT connollygeorgeadp agoutirelatedpeptideneuronalsilencingovercomesdelayedpubertyinneonatallyunderfedmalemice
AT ancelcaroline agoutirelatedpeptideneuronalsilencingovercomesdelayedpubertyinneonatallyunderfedmalemice
AT inglismegana agoutirelatedpeptideneuronalsilencingovercomesdelayedpubertyinneonatallyunderfedmalemice
AT andersongregm agoutirelatedpeptideneuronalsilencingovercomesdelayedpubertyinneonatallyunderfedmalemice