Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis

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dc.contributor.authorPinato, Luciana [UNESP]
dc.contributor.authorMachado, Sanseray da Silveira Cruz
dc.contributor.authorFranco, Daiane Gil
dc.contributor.authorCampos, Leila M. G.
dc.contributor.authorCecon, Erika
dc.contributor.authorFernandes, Pedro A. C. M.
dc.contributor.authorBittencourt, Jackson Cioni
dc.contributor.authorMarkus, Regina Pekelman
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2015-02-24T13:58:06Z
dc.date.available2015-02-24T13:58:06Z
dc.date.issued2013
dc.description.abstractAlthough melatonin is mainly produced by the pineal gland, an increasing number of extra-pineal sites of melatonin synthesis have been described. We previously demonstrated the existence of bidirectional communication between the pineal gland and the immune system that drives a switch in melatonin production from the pineal gland to peripheral organs during the mounting of an innate immune response. In the present study, we show that acute neuroinflammation induced by lipopolysaccharide (LPS) injected directly into the lateral ventricles of adult rats reduces the nocturnal peak of melatonin in the plasma and induces its synthesis in the cerebellum, though not in the cortex or hippocampus. This increase in cerebellar melatonin content requires the activation of nuclear factor kappa B (NF-κB), which positively regulates the expression of the key enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AA-NAT). Interestingly, LPS treatment led to neuronal death in the hippocampus and cortex, but not in the cerebellum. This privileged protection of cerebellar cells was abrogated when G-protein-coupled melatonin receptors were blocked by the melatonin antagonist luzindole, suggesting that the local production of melatonin protects cerebellar neurons from LPS toxicity. This is the first demonstration of a switch between pineal and extra-pineal melatonin production in the central nervous system following a neuroinflammatory response. These results have direct implications concerning the differential susceptibility of specific brain areas to neuronal death.en
dc.description.affiliationUniversidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Filosofia e Ciências - Campus de Marília, Marilia, Departamento de Fonoaudiologia, Av. Hygino Muzzi Filho ,737-, Câmpus Universitário, CEP 17525-900, SP, Brasil
dc.description.affiliationUnespUniversidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Filosofia e Ciências - Campus de Marília, Marilia, Departamento de Fonoaudiologia, Av. Hygino Muzzi Filho ,737-, Câmpus Universitário, CEP 17525-900, SP, Brasil
dc.identifierhttp://dx.doi.org/10.1007/s00429-013-0686-4
dc.identifier.citationBrain Structure and Function, December 2013.
dc.identifier.doi10.1007/s00429-013-0686-4
dc.identifier.fileISSN18632661-2013-01-14.pdf
dc.identifier.issn1863-2661
dc.identifier.lattes1924851134659071
dc.identifier.lattes8372363591179624
dc.identifier.urihttp://hdl.handle.net/11449/115466
dc.language.isoeng
dc.relation.ispartofBrain Structure and Function
dc.relation.ispartofsjr2,034
dc.rights.accessRightsAcesso aberto
dc.sourceCurrículo Lattes
dc.titleSelective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesisen
dc.typeArtigo
unesp.author.lattes1924851134659071
unesp.author.lattes8372363591179624
unesp.author.orcid0000-0001-7788-9205[1]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Filosofia e Ciências, Maríliapt

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Artigos - Fonoaudiologia - FFC