Non-N-Methyl-D-Aspartate Glutamate Receptors in Glial Cells and Neurons of the Pineal Gland in a Higher Primate

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Abstract
A role for glutamate in signalling mechanisms in the mammalian pineal gland is suggested by the high concentration of the transmitter in pinealocytes and the expression of glutamate receptor subunits in the rat gland. A single type of glutamate binding site has been characterized in the rat and bovine pineal gland, preferentially sensitive to the glutamate agonist α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), a potent inhibitor of melatonin synthesis in vitro. In order to investigate the anatomical basis of a putative role of glutamate in the pineal gland of a higher primate, we performed an immuno-histochemical analysis of the cellular localization of AMPA-type glutamate receptor subunits in the pineal gland of the macaque. Staining obtained with an antibody specific to GluRl receptor sub unit showed that this subunit is present in interstitial cells and astrocyte-like cells located in the parenchyma of the distal part of the gland. An antibody specific to GluR4 subunit stained astrocyte-like cells throughout the gland, however mainly in the proximal part, as well as a network of thin and long astrocytic-like processes located exclusively in the distal part of the gland. Staining obtained with an antibody recognizing both GluR2 and GluR3 subunits and the variant GluR4c exhibits a neuropilar-like pattern heterogeneously distributed throughout the gland. The three antibodies stained neuronal-like cells located mainly in the central part of the gland. These findings reveal that in the primate pineal gland, glutamate can act on glial cells via AMPA-gated receptor channels in unusual subunit configurations that likely underly high calcium permeability. Glutamate-induced responses in astrocytes may either regulate glutamatergic transmission by a stimulation of glutamate transport or modulate pinealocyte activity. Based on the existence of distinct glial subpopulations characterized by the differential distribution of AMPA-type receptor subunits, the anatomical division of the pineal gland into proximal and distal parts indicates a functional partition of the gland in higher primates. Intrapineal neuronal-like cells bearing AMPA-type receptors similar to those present in central neurons may be targets of a glutamatergic central neural input or of neighboring pinealocytes.

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