The melanin-concentrating hormone peptidergic system: a multiprotocolary approach to a multifunctional analysis

• Grant number: 23/02531-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2024
• End date: August 31, 2029
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Jackson Cioni Bittencourt
• Grantee: Jackson Cioni Bittencourt
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Cesar Augusto Pospissil Garbossa
• Associated researchers: Carlos Guerrero Bosagna ; Giovanne Baroni Diniz ; José de Anchieta de Castro e Horta Júnior ; Marcelo Alves da Silva Mori
• Associated scholarship(s): 24/22860-6 - Intracellular Signaling of Melanin-Concentrating Hormone in Mammary Gland Cells of Long-Evans Rats During the Lactation Period, BP.PD

Abstract

Introduction: the melanin-concentrating hormone [MCH] is a neuropeptide described as an orexigenic peptide. Other functions have been described, for instance: hypnogenesis, emotional state control, stress response, and sexual behavior. The production of MCH and its precursor messenger RNA [ppMCH RNAm] is concentrated in neurons of three diencephalic regions: the lateral hypothalamic area [LHA], the incerto-hypothalamic area [IHy], and the dorsolateral zona incerta [ZIdl]. Only during lactation, MCH-immunoreactive neurons [MCH-ir] and ppMCH mRNA expression appear in new hypothalamic territories, such as the ventromedial part of the medial preoptic area [MPOAvm]. The amount of MCH synthesis and the number of cells in this region increases with the progress of lactation, being maximum in the final phase, whereupon it disappears. A possible explanation for this phenomenon is the de novo appearance of cells in this region, which would characterize neurogenesis in the adult hypothalamus of lactating females. Other aspects relevant to the peptidergic system are: 1. the hodology of the MCH-ir cells of MPOAvm is not known; 2. the origin of breast innervation by MCH-producing centers is also unknown; 3. we did not find in the literature, in animals of a different taxonomic group and with greater proximity to humans, the description of MCH in the brain, for example in pigs, during the lactation period. Objectives: 1. Identify neurogenesis/neuroplasticity and neuronal maturation markers, during the lactation period in hypothalamic territories in rats; 2. Identify the genes expressed in MCH-ir cells, indicating whether there is de novo production of neurons or whether neuroplasticity of neurons already present in that region occurs in rats, during the lactation period; 3. Identify the diencephalic territories that innervate the breasts, and that eventually contain MCH-producing neurons and at the same time are marked with the Pseudorabies Virus [PRV] in rats; 4. Identify the nuclei that send outputs to the MPOAvm, and eventually are involved in the termination of maternal behavior and/or lactation, in rats; 5. To describe in a swine model the MCH neuropeptide family, possibly present in MPOAvm, during the lactation period, considering a comparative animal model; 6. To describe the markers of neurogenesis/neuroplasticity and neuronal maturation, observing what happens with MCH-ir cells that possibly appear during the lactation period in pigs; 7. To elucidate the effects of chronic stress on the peptidergic system of MCH, concerning its structure and physiology, in a swine model; 8. In a swine model, describe the differentially methylated regions and the genes involved in periods of neurogenesis or neuroplasticity of the MCH cells, as well as changes in the epigenome in response to stress. Rationale: both ppMCH mRNA and MCH neuropeptide are detected in new CNS sites in rats at the end of lactation. In this way, we would like to better understand the role of this neuropeptide as a presumable hormonal/neural control to terminate this period. Furthermore, to add knowledge about the hodology of the controlling centers of maternal behavior and/or lactation [in rodents], and finally, to contribute with an unprecedented study, by comparison in a different and non-rodent species, of the MCH neuropeptide family [in swine]. (AU)