Neuropeptide Y in the mammalian pineal gland.

The present review describes the anatomy of the neuropeptide (NPY)ergic innervation of the mammalian pineal gland with emphasis on the rat. The proNPY-molecule is post-translationally processed by a single cleavage to neuropeptide Y (NPY) and a C-terminal peptide of NPY (CPON). NPY is C-terminally amidated, and the amidation is essential for binding of NPY to its corresponding receptor(s). Since no proNPY has been detected in rat pineal extracts, it is considered that proNPY is immediately processed to its final products in the gland. In the rat, numerous NPY- and CPON-immunoreactive (ir) nerve fibers are present in the capsule of the superficial pineal gland and in the pineal parenchyma, mostly related to the connective tissue spaces and the vasculature of the gland, but also present between the pinealocytes. Furthermore, a substantial number of fibers was observed in the deep pineal gland, the pineal stalk, and the underlying epithalamus. Occasionally, NPY- or CPON-immunoreactive fibers were found adjacent to the stria medullaris and in the posterior commissure, which could be followed to the adjacent deep pineal gland. At the ultrastructural level, the NPY-immunoreactivity was confined in boutons containing large granular vesicles (100-200 nm) as well as small (40-60 nm) granular vesicles. Some terminals were located in very close apposition to the pinealocyte cell membrane. Terminals were identified in perivascular spaces, but synaptic contacts between the immunoreactive terminals and pinealocytes were never observed. These data show that NPY is highly concentrated in nerve fibers throughout the rat pineal complex. Double-fluorescence histochemistry using tyrosine hydroxylase as marker for catecholaminergic fibers and NPY revealed that nearly all NPYergic fibers co-stored tyrosine hydroxylase in the superficial pineal gland. A minor portion of both immunoreactivities was not colocalized. In accordance, about 65% of the neurons in the superior cervical ganglion contained both CPON and tyrosine hydroxylase. In bilateral superior cervical ganglionectomized rats, a few NPY-ir nerve fibers remained mostly in the pineal capsule, but few fibers were also found in the superficial pineal parenchyma. Contrarily, only a moderate decrease was observed in the number of immunoreactive fibers in the deep pineal gland, and no reduction was observed in the adjacent epithalamus. In the ganglionectomised rats, co-localisation of tyrosine hydroxylase and NPY in intrapineal nerve fibers was not observed either in the superficial pineal gland, nor in the deep pineal gland. These results together with the available literature show that NPY is a sympathetic transmitter, and its actions in the pineal gland are, therefore, associated with the well-documented roles of noradrenaline. Possible roles of NPY in pineal biochemistry and physiology are discussed.