Study of the anatomical basis for a volume transmission mechanism on the Melanin Concentrating Hormone [MCH] peptidergic system

• Grant number: 16/02748-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2016
• End date: September 30, 2019
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Jackson Cioni Bittencourt
• Grantee: Giovanne Baroni Diniz
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The Melanin-Concentrating Hormone [MCH] is a universal neuropeptide, virtually present in all known vertebrates studied, displaying a plethora of functions ranging from the regulation of skin pigmentation in teleost fish to sensorial integration and motivated behaviors modulation in mammals. This neuropeptide was mapped in the central nervous system [CNS] of some mammals, including ungulates, felines, simii and rodents. In this last group, however, its pattern of innervation was described for rats, but not for mice. Considering that many functional studies about MCH were made using mice as its animal model, it is fundamental that we understand the fine details of MCH anatomical characteristics in mice. Contrasting to the large body of information available about MCH, its receptors, MCHR1 and MCHR2, are still poorly understood, especially because rodents do not have subtype 2 of this receptor, which poses a huge challenge for its study. Aiming to elucidate the spatial distribution of MCH in the mice and to better characterize its receptors, we will employ immunohistochemistry [IHC] and in situ hybridization [ISH] to identify synthesis sites of these proteins and expression of their mRNA in the CNS of wild-type [WT], MCHR1-KO and MCHR2-GFP-KI [strain with a directed insertion of the human Mchr2 gene and its promoter sequence] mice. Up to this point, we have employed IHC to characterize the main sites of MCH synthesis and its main innervation fields in male and female mice in different stages of the reproductive cycle [diestrus, gestation and different moments of the lactation period]. We have also optimized our IHC protocols for MCHR1 immunoreactivity identification and employed them to map MCHR1 in male mice. The preliminary results we obtained so far suggest a putative mechanism for volume transmission in MCH signaling in the SNC of rats and mice. Additionally, we observed the presence of MCH peptidergic system elements in regions associated to neurogenesis in the adult brain. Considering the low amount of information available about MCH in these regions, we decided to investigate further the anatomical aspects of MCH in these areas employing, to that end, immunohistochemistry coupled to confocal and transmission electron microscopy, besides neuronal tracers. (AU)

Scientific publications

(13)

(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)

MOTTA-TEIXEIRA, LIVIA CLEMENTE; MACHADO-NILS, ALINE VILAR; BATTAGELLO, DANIELLA SABINO; DINIZ, GIOVANNE BARONI; ANDRADE-SILVA, JESSICA; SILVA JR, SINESIO; MATOS, RAPHAEL AFONSO; DO AMARAL, FERNANDA GASPAR; XAVIER, GILBERTO FERNANDO; BITTENCOURT, JACKSON CIONI; et al. The absence of maternal pineal melatonin rhythm during pregnancy and lactation impairs offspring physical growth, neurodevelopment, and behavior. Hormones and Behavior, v. 105, p. 146-156, SEP 2018. (12/04554-8, 16/02224-1, 16/02748-0, 10/52068-0, 14/22313-3, 14/50457-0, 16/18941-4)

SITA, LUCIANE V.; DINIZ, GIOVANNE B.; HORTA-JUNIOR, JOSE A. C.; CASATTI, CLAUDIO A.; BITTENCOURT, JACKSON C.. Nomenclature and Comparative Morphology of the Teneurin/TCAP/ADGRL Protein Families. FRONTIERS IN NEUROSCIENCE, v. 13, MAY 3 2019. (16/02748-0, 16/02224-1)

DINIZ, GIOVANNE B.; BITTENCOURT, JACKSON C.. The Melanin-Concentrating Hormone as an Integrative Peptide Driving Motivated Behaviors. FRONTIERS IN SYSTEMS NEUROSCIENCE, v. 11, MAY 29 2017. (16/02748-0, 10/52068-0)

PACHECO FERREIRA, JOZELIA GOMES; GOMES DUARTE, JESSICA CATHARINE; DINIZ, GIOVANNE BARONI; BITTENCOURT, JACKSON CIONI. Litter size determines the number of melanin-concentrating hormone neurons in the medial preoptic area of Sprague Dawley lactating dams. Physiology & Behavior, v. 181, p. 75-79, NOV 1 2017. (16/02224-1, 16/02748-0, 10/52068-0, 15/05990-4, 16/19845-9)

COSTA, HELDER C.; DA-SILVA, JOELCIMAR M.; DINIZ, GIOVANNE B.; MOTTA-TEIXEIRA, LIVIA C.; DA-SILVA, RENATA J.; BATTAGELLO, DANIELLA S.; SITA, V, LUCIANE; MACHADO, CARLA DE-MORAES; HORTA-JUNIOR, JOSE A. C.; BITTENCOURT, JACKSON C.. Characterisation and origins of melanin-concentrating hormone immunoreactive fibres of the posterior lobe of the pituitary and median eminence during lactation in the Long-Evans rat. Journal of Neuroendocrinology, v. 31, n. 9, SI, SEP 2019. (16/02224-1, 16/02748-0, 13/08618-3, 14/22313-3, 08/02771-6, 16/18941-4, 09/06769-9)

DINIZ, GIOVANNE B.; BITTENCOURT, JACKSON C.. The Melanin-Concentrating Hormone (MCH) System: A Tale of Two Peptides. FRONTIERS IN NEUROSCIENCE, v. 13, NOV 26 2019. (16/02748-0, 16/02224-1, 10/52068-0)

DINIZ, GIOVANNE B.; BATTAGELLO, DANIELLA S.; CHERUBINI, PEDRO M.; REYES-MENDOZA, JULIO D.; LUNA-ILLADES, CESAR; KLEIN, MARIANNE O.; MOTTA-TEIXEIRA, LIVIA C.; SITA, LUCIANE V.; MIRANDA-ANAYA, MANUEL; MORALES, TERESA; et al. Melanin-concentrating hormone peptidergic system: Comparative morphology between muroid species. JOURNAL OF COMPARATIVE NEUROLOGY, v. 527, n. 18, p. 2973-3001, DEC 15 2019. (16/02224-1, 16/02748-0, 14/22313-3, 17/17998-5, 16/18941-4, 17/16293-8)

DINIZ, GIOVANNE B.; BATTAGELLO, DANIELLA S.; KLEIN, MARIANNE O.; BONO, BIANCA S. M.; FERREIRA, JOZELIA G. P.; MOTTA-TEIXEIRA, LIVIA C.; DUARTE, JESSICA C. G.; PRESSE, FRANCOISE; NAHON, JEAN-LOUIS; ADAMANTIDIS, ANTOINE; et al. Ciliary melanin-concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex-independent manner. Journal of Neuroscience Research, v. 98, n. 10, JUN 2020. (15/05990-4, 16/02748-0, 17/16293-8, 17/17998-5, 16/18941-4, 16/19845-9, 16/02224-1, 14/22313-3)

ORECHIO, DAILIANY; AGUIAR, BRUNA ANDRADE; DINIZ, GIOVANNE BARONI; BITTENCOURT, JACKSON CIONI; HAEMMERLE, CARLOS A. S.; WATANABE, II-SEI; MIGLINO, MARIA ANGELICA; CASTELUCCI, PATRICIA. Morphological and Cellular Characterization of the Fetal Canine (Canis lupus familiaris) Subventricular Zone, Rostral Migratory Stream, and Olfactory Bulb. Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology, v. 301, n. 9, SI, p. 1570-1584, SEP 2018. (16/02224-1, 16/02748-0, 14/25927-2, 10/52068-0)

BATTAGELLO, DANIELLA S.; LORENZON, ALINE R.; DINIZ, GIOVANNE B.; MOTTA-TEIXEIRA, LIVIA C.; KLEIN, MARIANNE O.; FERREIRA, JOZELIA G. P.; ARIAS, CARLOS M.; ADAMANTIDIS, ANTOINE; SITA, V, LUCIANE; CIPOLLA-NETO, JOSE; et al. The Rat Mammary Gland as a Novel Site of Expression of Melanin-Concentrating Hormone Receptor 1 mRNA and Its Protein Immunoreactivity. FRONTIERS IN ENDOCRINOLOGY, v. 11, JUL 31 2020. (15/05990-4, 16/02748-0, 17/16293-8, 10/52068-0, 16/04210-8, 17/17998-5, 14/50457-0, 12/04554-8, 14/13052-1, 16/18941-4, 16/19845-9, 16/02224-1)

DINIZ, GIOVANNE B.; CANDIDO, PAULO L.; KLEIN, MARIANNE O.; ALVISI, RENATO D.; PRESSE, FRANCOISE; NAHON, JEAN-LOUIS; FELICIO, LUCIANO F.; BITTENCOURT, JACKSON C.. The weaning period promotes alterations in the orexin neuronal population of rats in a suckling-dependent manner. Brain Structure & Function, v. 223, n. 8, p. 3739-3755, NOV 2018. (17/17998-5, 16/02224-1, 16/02748-0, 10/52068-0)

BATTAGELLO, DANIELLA S.; DINIZ, GIOVANNE B.; CANDIDO, PAULO L.; DA SILVA, JOELCIMAR M.; DE OLIVEIRA, AMANDA R.; DA SILVA, KELLY R. TORRES; LOTFI, CLAUDIMARA F. P.; DE OLIVEIRA, JOSE A.; SITA, LUCIANE V.; CASATTI, CLAUDIO A.; et al. Anatomical Organization of Urocortin 3-Synthesizing Neurons and Immunoreactive Terminals in the Central Nervous System of Non-Human Primates [Sapajus spp.]. FRONTIERS IN NEUROANATOMY, v. 11, JUL 24 2017. (12/08833-9, 12/03067-6, 16/02224-1, 16/02748-0, 04/13849-5, 11/09816-8, 09/06769-9)

ORECHIO, DAILIANY; AGUIAR, BRUNA ANDRADE; DINIZ, GIOVANNE BARONI; BITTENCOURT, JACKSON CIONI; HAEMMERLE, CARLOS A. S.; WATANABE, II-SEI; MIGLINO, MARIA ANGELICA; CASTELUCCI, PATRICIA. Morphological and Cellular Characterization of the Fetal Canine (Canis lupus familiaris) Subventricular Zone, Rostral Migratory Stream, and Olfactory Bulb. Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology, v. 301, n. 9, p. 15-pg., 2018-09-01. (16/02748-0, 16/02224-1, 10/52068-0, 14/25927-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

DINIZ, Giovanne Baroni. Comparative morphology of the melanin-concentrating hormone system.. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.