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Induction of melatonin synthesis by glia and neurons in injured central nervous system


Extra-pineal production of melatonin induced by injury is being described in peripheral immune competent cells. Molecules that signalize injury, such as pro-inflammatory cytokines and PAMPs suppress pineal melatonin production and induce the synthesis of this indolamine by mononuclear and polymorphonuclear cells. The pivotal transcription factor in inflammatory responses, nuclear factor kappa B (NFKB), mediates both effects, ie, the suppression of pineal and the induction of immune-competent cells synthesis of melatonin due to cell specific activation of different subunits of NFKB. Taking into account that the glia cells are considered the immune-competent cells of the central nervous system (CNS), we investigated whether a shuttle between pineal and glia production of melatonin could be observed when the CNS is injured. As a matter of fact, intracerebroventricular injection of lipopolysaccharide (LPS) suppresses pineal melatonin production, and leads to a synthesis of this indolamine by the cerebellum. The present project was designed in order to determine which cells of the cerebellum produce melatonin and which is the mechanism of action of LPS. Our study will involve evaluating the effect of LPS and TNF on cultures of CNS cells regarding melatonin production and NFKB activation, and the effect of injected LPS and TNF in rats in order to analyze the changes in activity of glia and neurons by imunohistochemistry. Taking into account the immunomodulatory roles of tonin we will also evaluate the role of pineal and extra-pineal production during defense processes of the CNS. (AU)

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Scientific publications (16)
(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)
DA SILVEIRA CRUZ-MACHADO, SANSERAY; GUISSONI CAMPOS, LEILA MARIA; FADINI, CINTIA CRISTINA; ANDERSON, GEORGE; MARKUS, REGINA P.; PINATO, LUCIANA. Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances. Journal of Pineal Research, v. 70, n. 3 JAN 2021. Web of Science Citations: 3.
PINATO, LUCIANA; GALINA SPILLA, CAIO SERGIO; MARKUS, REGINA PEKELMANN; CRUZ-MACHADO, SANSERAY DA SILVEIRA. Dysregulation of Circadian Rhythms in Autism Spectrum Disorders. CURRENT PHARMACEUTICAL DESIGN, v. 25, n. 41, p. 4379-4393, 2019. Web of Science Citations: 1.
PINATO, LUCIANA; RIBEIRO, ERLANE M.; LEITE, REBEKA F. P.; LOPES, THAYSE F.; PESSOA, ANDRE L. S.; GUISSONI CAMPOS, LEILA M.; PIFFER, GIOVANNA E.; SOUZA, ANA L. D. M.; GIACHETI, CELIA M. Sleep findings in Brazilian children with congenital Zika syndrome. Sleep, v. 41, n. 3 MAR 2018. Web of Science Citations: 5.
GUISSONI CAMPOS, LEILA M.; HATAKA, ALESSANDRE; VIEIRA, ISIS Z.; BUCHAIM, ROGERIO L.; ROBALINHO, ISADORA F.; ARANTES, GIOVANNA E. P. S.; VIEGAS, JOYCE S.; BOSSO, HENRIQUE; BRAVOS, RAFAEL M.; PINATO, LUCIANA. Circadian Clock Proteins and Melatonin Receptors in Neurons and Glia of the Sapajus apella Cerebellum. FRONTIERS IN PHYSIOLOGY, v. 9, FEB 9 2018. Web of Science Citations: 3.
PINATO, LUCIANA; RAMOS, DAYANE; HATAKA, ALESSANDRE; ROSSIGNOLI, PATRICIA S.; GRANADO JUNIOR, MARCOS DONISETE; MAZZETTO, MARINA CARDOSO; CAMPOS, LEILA M. G. Day/night expression of MT1 and MT2 receptors in hypothalamic nuclei of the primate Sapajus apella. Journal of Chemical Neuroanatomy, v. 81, p. 10-17, APR 2017. Web of Science Citations: 7.
GUISSONI CAMPOS, LEILA MARIA; BUCHAIM, ROGERIO LEONE; DA SILVA, NATHANI CRISTINA; GALINA SPILLA, CAIO SERGIO; HATAKA, ALESSANDRE; PINATO, LUCIANA. Suprachiasmatic Nucleus and Subordinate Brain Oscillators: Clock Gene Desynchronization by Neuroinflammation. NEUROIMMUNOMODULATION, v. 24, n. 4-5, p. 231-241, 2017. Web of Science Citations: 4.
SANTORO, STELLA DONADON; GIACHETI, CELIA MARIA; ROSSI, NATALIA FREITAS; GUISSONI CAMPOS, LEILA MARIA; PINATO, LUCIANA. Correlations between behavior, memory, sleep-wake and melatonin in Williams-Beuren syndrome. Physiology & Behavior, v. 159, p. 14-19, MAY 15 2016. Web of Science Citations: 7.
PINTO, ALINE RODRIGUES; DA SILVA, NATHANI CRISTINA; PINATO, LUCIANA. Analyses of melatonin, cytokines, and sleep in chronic renal failure. Sleep and Breathing, v. 20, n. 1, p. 339-344, MAR 2016. Web of Science Citations: 8.
PINTO, ALINE RODRIGUES; DA SILVA, ROBERTA GONSALVES; PINATO, LUCIANA. Oropharyngeal swallowing in chronic renal failure. CoDAS, v. 28, n. 1, p. 71-76, JAN-FEB 2016. Web of Science Citations: 3.
ALINE RODRIGUES PINTO; ROBERTA GONÇALVES DA SILVA; LUCIANA PINATO. Deglutição orofaríngea na insuficiência renal crônica. CoDAS, v. 28, n. 1, p. -, Fev. 2016.
CAMPOS, LEILA M. G.; OSORIO, ELAINE C.; DA SILVA SANTOS, GRAZIELA LIGIA; NOGUEIRA, MARIA INES; CRUZ-RIZZOLO, ROELF J.; PINATO, LUCIANA. Temporal changes in calcium-binding proteins in the medial geniculate nucleus of the monkey Sapajus apella. Journal of Chemical Neuroanatomy, v. 68, p. 45-54, OCT 2015. Web of Science Citations: 2.
CAMPOS, L. M. G.; CRUZ-RIZZOLO, ROELF J.; PINATO, L. The primate seahorse rhythm. Brain Research, v. 1613, p. 81-91, JUL 10 2015. Web of Science Citations: 2.
FADINI, CINTIA C.; LAMONICA, DIONSIA A.; FETT-CONTE, AGNES C.; OSORIO, ELAINE; ZUCULO, GABRIELA M.; GIACHETI, CELIA M.; PINATO, LUCIANA. Influence of sleep disorders on the behavior of individuals with autism spectrum disorder. FRONTIERS IN HUMAN NEUROSCIENCE, v. 9, JUN 18 2015. Web of Science Citations: 16.
PINATO, LUCIANA; CRUZ-MACHADO, SANSERAY DA SILVEIRA; FRANCO, DAIANE G.; CAMPOS, LEILA M. G.; CECON, ERIKA; FERNANDES, PEDRO A. C. M.; BITTENCOURT, JACKSON C.; MARKUS, REGINA P. Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis. Brain Structure & Function, v. 220, n. 2, p. 827-840, MAR 2015. Web of Science Citations: 28.
CAMPOS, L. M. G.; CRUZ-RIZZOLO, R. J.; WATANABE, II-SEI; PINATO, L.; NOGUEIRA, M. I. Efferent projections of the suprachiasmatic nucleus based on the distribution of vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP) immunoreactive fibers in the hypothalamus of Sapajus apella. Journal of Chemical Neuroanatomy, v. 57-58, p. 42-53, MAY 2014. Web of Science Citations: 10.
GABRIELA MELLONI ZUCULO; CINTIA CRISTINA FADINI KNAP; LUCIANA PINATO. Correlation between sleep and quality of life in cerebral palsy. CoDAS, v. 26, n. 6, p. 447-456, Dez. 2014.

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