Modulation of Pineal Melatonin Synthesis by Glutamate Involves Paracrine Interactions between Pinealocytes and Astrocytes through NF-kappa B Activation

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Villela, Darine ; Atherino, Victoria Fairbanks ; Lima, Larissa de Sa ; Moutinho, Anderson Augusto ; do Amaral, Fernanda Gaspar ; Peres, Rafael ; de Lima, Thais Martins ; Torrao, Andrea da Silva ; Cipolla-Neto, Jose ; Scavone, Cristoforo ; Afeche, Solange Castro

• Tipo de documento: Artigo Científico
• Fonte: BIOMED RESEARCH INTERNATIONAL; v. 2013, p. 14-pg., 2013-01-01.

Resumo

The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF-kappa B activation were analyzed in astrocytes and pinealocytes. TNF-alpha's possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF-alpha. Moreover, the activation of the astrocytic NF-kappa B seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF-kappa B transcription factor and possibly by subsequent TNF-alpha release. (AU)

• Processo FAPESP: 04/04328-1 - Sintese de melatonina na glandula pineal de ratos: modulacao pelo glutamato.
• Beneficiário: Solange Castro Afeche
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 05/56943-4 - Sinalizacao intracelular glutamatergica e sintese de melatonina na glandula pineal de ratos: influencia do oxido nitrico e dos fatores de transcricao nf-kb e creb.
• Beneficiário: Darine Christina Maia Villela
• Modalidade de apoio: Bolsas no Brasil - Mestrado