Retour au formulaire de recherche

Kisspeptin and the rhythm of energy balance in reproduction

Unité de Recherche

UPR 3212 - Institut des Neurosciences Cellulaires et Intégratives (INCI)
5, rue Blaise Pascal, 67084 STRASBOURG

Équipe

Nom : Melatonine et Rythmes saisonniers

Responsable : SIMONNEAUX Valerie - simonneaux@inci-cnrs.unistra.fr

Téléphone du responsable : 0388456671

Composition de l'équipe :
- Chercheurs : 4
- ITA : 2
- Doctorants : 5
- Post-Docs : 2
- Autres : 0

Publications majeures de l'équipe relatives au sujet au cours des 3 dernières années (le cas échéant, 3 publications récentes du DT) :
1) Henningsen JB, Poirel VJ, Mikkelsen JD, Tsutsui K, Simonneaux V and Gauer F (2015) Sex differences in the photoperiodic regulation of RF-amide related peptide (RFRP)and its receptor GPR147 in the Syrian hamster. J. Comp Neurol, in press
2) Chassard D, Bur I, Poirel VJ, Mendoza J and Simonneaux V (2015) Evidence for a Putative Circadian Kiss-Clock in the Hypothalamic AVPV in Female Mice. Endocrinology, 156: 2999-3011
3) Sáenz de Miera C, Monecke S, Bartzen-Sprauer J, Laran-Chich MP, Pévet P, Hazlerigg D, Simonneaux V (2014). A circannual clock drives expression of genes central for seasonal reproduction. Current Biology, 24(13):1500-1506

Concernant la thèse

Directeur de Thèse : SIMONNEAUX Valerie - simonneaux@inci-cnrs.unistra.fr

Téléphone : 03 88 45 66 71

Co-encadrant : non

Co-tutelle : oui

Co-Directeur : KALSBEEK Andries
Université du Co-Directeur : Université of Amsterdam

Concernant le sujet proposé :

Titre : Kisspeptin and the rhythm of energy balance in reproduction

Projet : Rationale: The hypothalamic neuropeptide kisspeptin (Kp) is a potent activator of GnRH neurons that control the reproductive activity (Pinilla et al., 2012). This peptide governs not only puberty onset but also the daily, estral/menstrual, and seasonal rhythm in reproduction (Simonneaux et al., 2013). Reproductive success is tightly dependant on the metabolic status, especially in female mammals. In line with this, Kp neurons are now recognized as the central pathway responsible for conveying key homeostatic information to GnRH neurons (De Bond and Smith, 2014). A number of studies have shown that metabolic modulators (leptin, POMC, NPY) regulate Kp neurons. Alternatively, it is also possible that Kp impacts on metabolic functions.

Aim: In this project we will investigate whether Kp may regulate directly or indirectly central and peripheral structures involved in the daily and seasonal control of energy metabolism.

The first part of the project will analyze the effect of acute central injection of Kp on glucose and lipid metabolism, as well as the secretion of metabolic hormones (insulin, leptin, ghrelin). Because the metabolic challenge is higher in female than male reproduction, the Kp effect will be compared between both sexes. Furthermore, because both Kp expression and food intake display daily variation, the effect of Kp will be tested at different times of the day to determine whether its metabolic effect is time-dependant. This part of the project will be performed in Dr KalsbeekÂ’s lab (Amsterdam) for 11 months (November 2016 - September 2017)

The second part of the project will disclose the cellular targets for the metabolic effects of Kp. It has been shown that Kp neurons are anatomically linked to POMC and NPY neurons. Therefore the effect of Kp injection on neuronal activity and peptide encoding gene expression will be tested in POMC and NPY neurons, but also in somatostatin and orexin neurons. The dose and time of injection will be determined according to the results in the first study. Furthermore, the putative localization of Kp receptors on these neurons will be examined by dual labeling techniques. This part of the project will be performed in Dr KalsbeekÂ’s lab (Amsterdam) for 6 months (October 2017-March 2018) and Dr SimonneauxÂ’s lab (Strasbourg) for 6 months (April 2018-September 2018)

The third part of the project will evaluate the metabolic effects of Kp in seasonal rodents. Kp expression is highly regulated by the photoperiodic variation in the pineal hormone melatonin and these variations are critical to drive seasonal reproduction (Simonneaux et al., 2013). In addition to displaying a clear seasonal variation in reproductive activity, many seasonal rodents also display marked seasonal variation in food intake and body weight. This last part of the study will test the hypothesis that Kp is involved in the seasonal regulation of food intake and body weight in male and female Siberian hamsters. Hamsters will be adapted to either an inhibitory short photoperiod (quiescent reproduction, low food intake and body weight) or stimulatory long photoperiod (sexually active, high food intake and body weight) and they will be given chronic icv infusion of Kp or vehicle for 6 weeks, while sexual activity (gonadotropin secretion), food intake and body weight will be followed at regular intervals. At the end of the chronic experiment, brains will be examined for orexigenic and anorexigenic peptide expression. In peripheral tissues, such as liver, white and brown adipose tissue and muscle, gene expression will be measured to investigate the underlying mechanism for the changes in energy metabolism. This part of the project will be performed Dr SimonneauxÂ’s lab (Strasbourg) for 7 months (October 2018 - Avril 2019) and Dr KalsbeekÂ’s lab (Amsterdam) for 4 months (May 2019 - August 2019).

Compétences souhaitées : Education in mammalian neuroendocrinolgy and neuroscience is a strong advantage.
A good background in neuroanatomy and in vivo physiology is preferred.
Experience with working with experimental animals is necessary.
The student should be independent and flexible in order to adapt to different environments

Expertises qui seront acquises au cours de la formation : Small rodent surgery, acute and chronic intracerebral injections, hormone assays, immunhistochemistry, in situ hybridization, peptide pharmacology