Investigation into the action of the Melanin-Concentrating Hormone in Motivated Systems of Maternal Behavior

• Grant number: 25/13454-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2025
• End date: June 30, 2029
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Jackson Cioni Bittencourt
• Grantee: Allan dos Anjos Monteiro
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/02531-5 - The melanin-concentrating hormone peptidergic system: a multiprotocolary approach to a multifunctional analysis, AP.TEM

Abstract

Introduction: Lactation is a process that involves different central and peripheral control systems, promoting a wide range of changes in the behavior and relationship between the mother and her offspring, characterizing maternal behavior. This period is divided into three phases: onset, maintenance, and decline. The decline phase is marked, among other factors, by the mother's withdrawal and rejection of her offspring. However, the neural mechanisms that regulate the approach-withdrawal binary are still poorly understood. In this context, the literature suggests a possible central role of the melanin-concentrating hormone [MCH], encoded by the Pmch gene, in the regulation of the different phases of the postpartum period. MCH presents distinct patterns of expression in two regions: the lateral hypothalamic area [MCH-LHA] and the ventromedial preoptic area [MCH-MPOAvm], the latter being expressed transiently only during the decline period. However, the mechanisms by which MCH influences the transition between these phases throughout lactation and the late postpartum period, as well as the role of MCH-immunoreactive neuron populations [MCH-ir] in both regions, are still unknown. Objective: To characterize the expression of MCH mRNA in hypothalamic territories [LHA and MPOAvm] during different stages of maternal behavior in the postpartum and lactation periods. Materials and Methods: 250 rats (Rattus norvegicus) will be used, distributed in 10 experimental groups, composed of virgin females and females on postpartum days (postpartum day, PPD-1, PPD-3, PPD-5, PPD-8, PPD-10, PPD-12, PPD-17, PPD-19 and PPD-23), with 25 animals per group. The expression of the genes Oxtr (oxytocin receptor), Pmch (melanin-concentrating hormone), Mchr1 (MCH receptor), Prlr (prolactin receptor) in the LHA and MPOAvm regions will be quantified by real-time quantitative polymerase chain reaction (RT-qPCR). In parallel, public single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) data from the LHA, MPOAvm regions and target areas of these respective areas (datasets GSE125065, GSE130597, GSE169176, GSE113576, GSE278848 and GSE246717) will be integrated, with batch effect correction by the HARMONY algorithm. Gene coexpression network analyses will be applied using high-dimensional Weighted Gene Coexpression Network Analysis (hdWGCNA), and cell-cell interaction inference will be conducted using CellChat version 2 (v2) and COMMOT tools. Contributions: With this project, we seek to elucidate poorly understood mechanisms regarding the role of MCH in the maternal motivated behavior system with the offspring during the postpartum period. We intend to explore the role of MCH-ir neurons in the LHA and MPOAvm, bringing new insights into possible neurogenic and/or neuroplasticity mechanisms and their implications in maternal behavior.