Peptidergic peripheral nervous systems in the mammalian pineal gland

The distribution and density of tyrosine hydroxylase (TH) and neuropeptide Y (NPY)-immunoreactive, sympathetic fibers and calcitonin gene-related peptide (CGRP)-, substance P (SP)-, and vasoactive intestinal polypeptide (VIP)-immunoreactive, non-sympathetic fibers in the pineal gland, the effects of superior cervical ganglionectomy (SCGX) on these fibers, and the location of their terminals in the pineal gland were compared between rodents and non-rodents. A dense network of TH/NPY-positive fibers is present all over the pineal gland. A less dense network of CGRP/SP- or VIP-positive fibers occurs in the whole pineal gland of non-rodents, but these fibers are usually confined to the superficial pineal gland in rodents. After SCGX, some TH/NPY-fibers remain only in the deep pineal gland in rodents, whereas considerable numbers of these fibers persist throughout the gland in non-rodents. Thus, the remaining fibers, probably originating from the brain, may be more numerous in non-rodents. Since CGRP-, SP- or VIP-immunoreactive fibers in the pineal capsule can be traced to those in the gland, and since these fibers are ensheathed by Schwann cells, it is concluded that these fibers belong to the peripheral nervous system. However, the existence of SP-positive central fibers cannot be denied in some species. In the superficial pineal gland of rodents, sympathetic terminals are mostly localized in perivascular spaces, whereas the parenchymal innervation by sympathetic fibers in the pineal gland is more dense in non-rodents than in rodents. Synapses between sympathetic nerve terminals and pinealocytes occur occasionally in non-rodents, but only rarely in the superficial pineal gland of rodents. The occurrence of the synapses may depend on the frequency of intraparenchymal sympathetic terminals.