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BioMed Research International
Volume 2013 (2013), Article ID 618432, 14 pages
Research Article

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

1Laboratory of Pharmacology, Butantan Institute, Avenida Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil
2Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo Avenida Professor Lineu Prestes 1524, 05508-900 São Paulo, SP, Brazil
3Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 1524, 05508-900 São Paulo, SP, Brazil

Received 26 April 2013; Accepted 28 June 2013

Academic Editor: Alejandro Lomniczi

Copyright © 2013 Darine Villela et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-κB activation were analyzed in astrocytes and pinealocytes. TNF-α'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-α. Moreover, the activation of the astrocytic NF-κB 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-κB transcription factor and possibly by subsequent TNF-α release.