The existence of neurogenesis during the lactation period

• Grant number: 16/02224-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: August 01, 2017
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• 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
• Associated research grant(s): 19/23577-8 - Do melanin-concentrating hormone (MCH) and ghrelin interact to modulate lactation terminus?, AP.R SPRINT; 18/15250-6 - Neuroendocrine regulation on the neural networks for adaptive social behavior in postpartum females, AP.R SPRINT; 17/16293-8 - The existence of neurogenesis during the lactation period - multiuser equipment approved in Fapesp Grant number 2016/02224-1: confocal microscope, brand Zeiss, model LSM 800, AP.EMU
• Associated scholarship(s): 22/14595-5 - EVALUATION OF VARIATION OF PRE-PRO-HORMONE MELANIN- CONCENTRATING AND NEUROGENESIS mRNA IN MEDIAL PRE-OPTIC AND LATERAL HYPOTHALAMIC AREAS OF LACTATING RATS IN RELATION TO CORTICOSTERONE LEVELS, BP.IC; 22/04171-3 - Influence of the offspring sex on the energetic balance and neurons immunoreactive to the melanin concentrating hormone in the medial preoptic area of lactating rats, BP.IC; 19/17239-2 - Adult Neurogenesis during Lactation and Maternal Behavior: Implications of melanin-concentrating hormone (MCH) and Melatonin, BP.PD; + associated scholarships 20/06939-0 - The existence of neurogenesis during the lactation period, BP.PD; 18/11527-3 - "Characterization of melanin-concentrating hormone receptor 1 (MCHR1) signaling pathways and analysis of hormonal influence on the function of the MCH peptidergic system in mammary epithelial cell culture", BP.PD; 17/18019-0 - Regulatory role investigation of melanin-concentrating hormone (MCH) in Long-Evans rats lactation: inhibition effects of the Pmch gene by iRNA technique, BP.PD; 17/17998-5 - Evaluating chronic administration of melanin concentrating hormone (MCH) effects in lactating Long-Evans rats, BP.PD - associated scholarships

Abstract

The Melanin-Concentrating Hormone [MCH] is an important neuropeptide, implied in a plethora of functions. Exclusively during the lactation period MCH-ir neurons and ppMCH mRNA are detected in new hypothalamic territories, as the ventromedial preoptic area [MPOAvm]. MCH synthesis in this region rises as the lactation progresses, reaching its peak at the final stage [around the 19th - 21st days] when it then disappears. The origin of these cells is still unknown. A possible explanation to this phenomenon is the de novo appearance of cells in this region, which would characterize neurogenesis in the adult hypothalamus of lactating female rats. Goal: to identify the origin of MCH-ir cells that appear in the MPOAvm during the lactation period, making a global evaluation of neurogenesis occurrence in the maternal brain. Additionally, to study the impact that MCH has over feeding and maternal behavior of lactating females. Rationale: Since both the ppMCH mRNA and the MCH peptide are detected in new loci of the rat CNS at later stages of lactation, we would like to unravel the role played by this neuropeptide over a possible control of hormonal/neuronal aspects of lactation termination, besides other possible neurogenic niches in the maternal brain. Material and Methods: to evaluate MCH participation in the lactation period: 1) female rats will receive sequential BrdU injections and will be sacrificed in different lactation stages. Their brains will then be used in immunohistochemistry for the identification of multiple markers of neurogenesis and neuronal maturation; 2) through osmotic minipumps, lactating females will receive chronic infusions of MCH during the entire lactation period and its effects will be evaluated through immunohistochemistry, in situ hybridization, western blotting, qRT-PCR, behavioral analysis and milk withdraw; 3) RNA interference [RNAi] will be used to inhibit the Pmch gene function, both in the LHA and in the MPOA of lactating females and, through that, we will analyze its effects on maternal and feeding behavior. (AU)

Scientific publications

(26)

(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)

CAMPOS, ANA M. P.; TEIXEIRA, PRYSCILA D. S.; WASINSKI, FREDERICK; KLEIN, MARIANNE O.; BITTENCOURT, JACKSON C.; METZGER, MARTIN; DONATO, JR., JOSE. Differences between rats and mice in the leptin action on the paraventricular nucleus of the hypothalamus: Implications for the regulation of the hypothalamic-pituitary-thyroid axis. Journal of Neuroendocrinology, AUG 2020. (16/20897-3, 16/02224-1, 17/16473-6, 17/02983-2, 17/17998-5)

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. (16/02224-1, 17/18019-0, 17/17998-5)

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)

KRONKA SOSTHENES, MARCIA CONSENTINO; DINIZ, DANIEL GUERREIRO; ROODSELAAR, JAY; ABADIE-GUEDES, RICARDO; CHAVES DE SIQUEIRA MENDES, FABIOLA DE CARVALHO; FERNANDES, TAIANY NOGUEIRA; BITTENCOURT, JACKSON CIONI; PICANCO DINIZ, CRISTOVAM WANDERLEY; ANTHONY, DANIEL CLIVE; ARAUJO GUEDES, RUBEM CARLOS. Stereological Analysis of Early Gene Expression Using Egr-1 Immunolabeling After Spreading Depression in the Rat Somatosensory Cortex. FRONTIERS IN NEUROSCIENCE, v. 13, SEP 25 2019. (10/52068-0, 16/02224-1)

WASINSKI, FREDERICK; KLEIN, MARIANNE O.; BITTENCOURT, JACKSON C.; METZGER, MARTIN; DONATO JR, JOSE. Distribution of growth hormone-responsive cells in the brain of rats and mice. Brain Research, v. 1751, JAN 15 2021. (16/20897-3, 16/02224-1, 17/16473-6, 17/17998-5, 17/02983-2)

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)

TEIXEIRA, PRYSCILA D. S.; WASINSKI, FREDERICK; LIMA, LEANDRO B.; FRAZAO, RENATA; BITTENCOURT, JACKSON C.; DONATO JR, JOSE. Regulation and neurochemical identity of melanin-concentrating hormone neurones in the preoptic area of lactating mice. Journal of Neuroendocrinology, v. 32, n. 2, DEC 2019. (16/20897-3, 17/21840-8, 17/02983-2, 16/02224-1)

CAMPOS, ANA M. P.; WASINSKI, FREDERICK; KLEIN, MARIANNE O.; BITTENCOURT, JACKSON C.; METZGER, MARTIN; DONATO JR, JOSE. Fasting reduces the number of TRH immunoreactive neurons in the hypothalamic paraventricular nucleus of male rats, but not in mice. Neuroscience Letters, v. 752, MAY 1 2021. (16/02224-1, 17/16473-6, 17/17998-5, 16/20897-3)

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)

GOBBO, DENISE RIBEIRO; PEREIRA, LAIS DA SILVA; PACHECO FERREIRA, JOZELIA GOMES; DE CASTRO HORTA-JUNIOR, JOSE ANCHIETA; BITTENCOURT, JACKSON CIONI; SA, SUSANA ISABEL. Effects of ovariectomy on the inputs from the medial nucleus of the amygdala to the ventromedial nucleus of the hypothalamus in young adult rats. Neuroscience Letters, v. 746, FEB 16 2021. (16/02224-1, 10/52068-0, 15/05990-4)

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)

MALTA, MARILIA B.; MARTINS, JOELCIMAR; NOVAES, LEONARDO S.; DOS SANTOS, NILTON B.; SITA, LUCIANE; CAMARINI, ROSANA; SCAVONE, CRISTOFORO; BITTENCOURT, JACKSON; MUNHOZ, CAROLINA D.. Norepinephrine and Glucocorticoids Modulate Chronic Unpredictable Stress-Induced Increase in the Type 2 CRF and Glucocorticoid Receptors in Brain Structures Related to the HPA Axis Activation. Molecular Neurobiology, v. 58, n. 10, JUL 2021. (12/24002-0, 16/02224-1, 12/24727-4, 10/52068-0, 10/13843-8, 16/03572-3)

OH, JUN; PETERSEN, CATHRINE; WALSH, CHRISTINE M.; BITTENCOURT, JACKSON C.; NEYLAN, THOMAS C.; GRINBERG, LEA T.. The role of co-neurotransmitters in sleep and wake regulation. MOLECULAR PSYCHIATRY, v. 24, n. 9, p. 1284-1295, SEP 2019. (16/02224-1)

PEREIRA, LAIS DA SILVA; GOBBO, DENISE RIBEIRO; FERREIRA, JOZELIA GOMES PACHECO; HORTA-JUNIOR, JOSE DE ANCHIETA DE CASTRO E; SA, SUSANA ISABEL; BITTENCOURT, JACKSON CIONI. Effects of ovariectomy on inputs from the medial preoptic area to the ventromedial nucleus of the hypothalamus of young adult rats. Journal of Anatomy, v. 238, n. 2, SEP 2020. (16/02224-1, 10/52068-0, 16/13136-6)

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)

OH, JUN; ESER, RANA A.; EHRENBERG, ALEXANDER J.; MORALES, DULCE; PETERSEN, CATHRINE; KUDLACEK, JESSICA; DUNLOP, SARA R.; THEOFILAS, PANOS; RESENDE, ELISA D. P. F.; COSME, CELICA; et al. Profound degeneration of wake-promoting neurons in Alzheimer's disease. ALZHEIMERS & DEMENTIA, v. 15, n. 10, p. 1253-1263, OCT 2019. (16/02224-1)

DUARTE, JESSICA CATHARINE GOMES; FERREIRA, JOZELIA GOMES PACHECO; BITTENCOURT, JACKSON CIONI. Melanin-concentrating hormone regulation by estradiol and progesterone in the incerto-hypothalamic area. Peptides, v. 163, p. 10-pg., 2023-02-15. (16/02224-1)

BITTENCOURT, JACKSON C.. Anatomical and functional heterogeneity of 'hypothalamic' peptidergic neuron populations. NATURE REVIEWS ENDOCRINOLOGY, v. 18, n. 7, p. 1-pg., 2022-04-25. (16/02224-1)

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)

CAMPOS, ANA M. P.; TEIXEIRA, PRYSCILA D. S.; WASINSKI, FREDERICK; KLEIN, MARIANNE O.; BITTENCOURT, JACKSON C.; METZGER, MARTIN; DONATO, JOSE, JR.. Differences between rats and mice in the leptin action on the paraventricular nucleus of the hypothalamus: Implications for the regulation of the hypothalamic-pituitary-thyroid axis. Journal of Neuroendocrinology, v. 32, n. 9, p. 11-pg., 2020-08-24. (16/02224-1, 17/17998-5, 16/20897-3, 17/02983-2, 17/16473-6)