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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Pinato, Luciana [1, 2] ; Cruz-Machado, Sanseray da Silveira [1] ; Franco, Daiane G. [1] ; Campos, Leila M. G. [3] ; Cecon, Erika [1] ; Fernandes, Pedro A. C. M. [1] ; Bittencourt, Jackson C. [3] ; Markus, Regina P. [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biosci, Dept Physiol, Lab Chronopharmacol, BR-05508090 Sao Paulo, SP - Brazil
[2] Sao Paulo State Univ UNESP, Dept Speech Language & Hearing Therapy, BR-17525900 Marilia, SP - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508900 Sao Paulo, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Brain Structure & Function; v. 220, n. 2, p. 827-840, MAR 2015.
Citações Web of Science: 28
Resumo

Although 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-kappa B), 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. (AU)

Processo FAPESP: 04/13849-5 - Circuitos peptidérgicos envolvidos na organização do comportamento alimentar
Beneficiário:Jackson Cioni Bittencourt
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 07/07871-6 - Eixo Imune-Pineal: produção endócrina e parácrina de melatonina em condições de injúria
Beneficiário:Regina Pekelmann Markus
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 11/51495-4 - Produção de melatonina por células do sistema nervoso central em condições de injúria
Beneficiário:Luciana Pinato
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores