The putative envolvement of melanin-concentrating hormone in the control of lactation

Abstract

Twenty years have passed since the neuropeptide known as melanin-concentrating hormone (MCH) was discovered in mammals. During that time, much has been done in order to elucidate the functions in which MCH is involved. Studies have shown that MCH can function as an orexigenic peptide, as well as playing a role in the control of sensory information, in the reward from food intake, in learning, in memory and in many other functions. In the rat, the prepro-MCH (ppMCH) mRNA and the MCH and NEI peptides are primarily located in the neurons of two central nervous system (CNS) regions: the lateral hypothalamic area and the incerto-hypothalamic area. The axons of those neurons are distributed along the length of the neural axis, including here the median eminence and the posterior lobe of the hypophyisis. However, novel sites of prepro-MCH expression and immunoreactivity (MCH-ir) have been identified in other hypothalamic nuclei, such as the ventral part of medial preoptic area (MPOAv), where such expression has been shown to occur during the final portion of the lactation period (from day 19 to day 21). Nevertheless, very little attention has been given to increase the understanding of the role that MCH plays in maternal behavior (MB). Goal: The objective of this project is to generate additional data on the participation of MCH in the control of lactation, thereby increasing the knowledge regarding the control of MB. Rationale: In lactating rat dams, prepro-MCH and its neuropeptides appear In the MPOAv, specifically near the end of the lactation period, besides the previously mentioned regions, i.e, the LHA and IHy. Therefore, there is a need to improve understanding of the hormonal/neural controls for the termination/continuation of lactation. Material and Methods: In order to study the possible involvement of MCH in MB, we will use transmission electron microscopy of the MCH-ir axons/terminals that traverse the median eminence (internaI lamina), determining their relationship with oxytocinergic axons/terminals, as well as of those found in the posterior lobe of the hypophysis, and it will be analyzed the ultrastructure of the MCH-ir neurons in the MPOAv; we will cannulate the MPOAv and inject it with interference RNA, which will allow us to study the termination/continuation of lactation; using Phaseolus vulgaris leucoagglutinin as an anterograde neuronal tracer, we will also study the efferents of the MPOAv, looking at the targeted areas in order to infer the possible MB-related functions of this specific subdivision; in addition, we will analyze the serum levels of MCH, prolactin, oxytocin and other hormones/neurotransmitters related to lactation, in order to evaluate the relationship between each of those substances and this aspect of MB; we will also use microarray technology in order to study the distribution of the subtypes of the glutamate receptor N-methyl-d-aspartate in MCHergic neurons during the lactation phase. (AU)