Regulatory role investigation of melanin-concentrating hormone (MCH) in Long-Evans rats lactation: inhibition effects of the Pmch gene by iRNA technique

• Grant number: 17/18019-0
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): November 01, 2017
• Effective date (End): October 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Jackson Cioni Bittencourt
• Grantee: Ariel Rodrigues Cardoso
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/02224-1 - The existence of neurogenesis during the lactation period, AP.TEM

Abstract

The synthesis of melanin-concentrating hormone [MCH] in the ventromedial pre-optic area [MPOAvm] increases intensely around the 19th day of lactation of rats. The role of this activation has not yet been fully uncovered, and its function is largely unknown in maternal physiology. MCH is produced by processing the precursor preproMCH [ppMCH], which encodes two other neuropeptides, the NEI and the NGE. In addition, MCH activity depends on its binding to its receptor [MCHR1], which is coupled to different types of G proteins, specific for each cell type, which can activate MAP kinases, decrease cAMP concentration and / or increase concentration of cytosolic Ca2 +. In this work, we propose to investigate the activation of ppMCH mRNA expression on maternal behavior and energetic homeostasis through the RNA interference technique [RNAi], inhibiting Pmch gene expression or MCHR1 receptor activity. In parallel, pharmacological inhibition of the MCHR1 receptor will be performed by the use of the competitive antagonist H-6408 [BACHEM, Germany]. Intracerebral injections in the lateral hypothalamic area [LHA] or MPOAvm in lactating rats of the appropriate short interfering RNAs [siRNAs] and randomized [scrambled] or "empty" controls will be performed. The brain will then be processed for biochemical and neurochemical identification techniques such as single or double label immunohistochemistry and in situ hybridization. In addition, rats will be filmed for behavioral analysis and parameters related to food consumption will be monitored daily. Therefore, this study allows a more extensive understanding of the peptidergic system of HCM during the lactation process in rats.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KLEIN, MARIANNE O.; BATTAGELLO, DANIELLA S.; CARDOSO, ARIEL R.; HAUSER, DAVID N.; BITTENCOURT, JACKSON C.; CORREA, RICARDO G. Dopamine: Functions, Signaling, and Association with Neurological Diseases. Cellular and Molecular Neurobiology, v. 39, n. 1, p. 31-59, JAN 2019. Web of Science Citations: 6.