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On GABA metabolism in the gliocyte cells of the rat pineal gland.

The uptake of the inhibitory transmitter substance gamma-aminobutyric acid (GABA) into the adult rat pineal gland was studied autoradiographically using both light and electron microscopy. The sites of GABA uptake were shown to be exclusively present in the gliocyte cells of the gland following both in vitro incubation with tritiated GABA and after in vivo administration of the amino acid by intra-arterial injection. Both the pinealocyte cells and the numerous sympathetic axons in the gland were devoid of silver grains. Preliminary biochemical studies indicated that the gliocyte uptake process for GABA resembles that in the satellite glia of the sensory ganglia but differed from that in slices of the cerebral cortex. Evidence is also presented which shows the pineal gland to contain endogenous GABA and the enzymes directly associated with its in vivo metabolism, L-glutamate-1-carboxylase (EC 4.1.1.15) (GAD) and GABA-2-oxoglutarate aminotransferase (EC 2.6.1.19) (GABA-T). Furthermore, a 3-fold rise in endogenous GABA occurred in the pineal after inhibition of GABA-catabolism as would be expected if the GABA-shunt pathway was functionally active in the oxidative metabolism of the pineal gland.

Aminobutyrates↗

Adrenal-mediated depression of N-acetyltransferase activity and melatonin levels in the rat pineal gland.

N-acetyltransferase (NAT) is believed to be the rate-limiting enzyme in the synthesis of melatonin from serotonin in the pineal gland. Norepinephrine released from sympathetic nerve endings within the pineal gland stimulates NAT activity and, therefore, melatonin synthesis. When an animal is subjected to a stressful stimulus, it would be expected that the increase in plasma stimulus, it would be expected that the increase in plasma catecholamines originating from the adrenal medulla and/or the sympathetic nervous system would result in a stimulation of pineal NAT activity. Adult male rats were given a 1.5cc injection of physiological saline subcutaneously into the back leg. Compared to non-injected controls, animals stressed in this manner were shown to have significantly lower pineal melatonin content 10 min after the saline injection late in the light phase of the light/dark cycle (at 18.30 h-lights on at 07.00 h). To test this more thoroughly, a time course study was conducted during the dark phase (at 02.00 h-5 hours after lights out) when pineal NAT activity and melatonin levels are either increasing or elevated. NAT activity and melatonin levels in the pineal were significantly depressed in stressed animals as compared to controls by 10 min after the saline injection, and remained so until 60 min after injection. By 90 min they had returned to control values. In the next study the nighttime response of the pineal to stress was compared in intact and adrenalectomized rats. Adrenalectomy prevented the changes in NAT activity and melatonin content associated with the saline injection. Some factor, such as a catecholamine or corticosterone from the adrenal, seems to be eliciting the response in the pineal to the saline injection. It is not known if the factor is acting centrally or directly on the pineal gland.

Acetyltransferases↗

Does the pineal gland have a role in the psychological mechanisms involved in the progression of cancer?

Psychological factors, e.g., depression and psychological stress have been implicated in the progress of cancer. Similarly, the pineal gland and its principal secretion, melatonin, are known to influence the initiation and progress of cancer. Furthermore, changes in melatonin secretion have been linked with psychological stress and depression, and both the pineal gland and the cerebral cortex act via the limbic system in producing their effects. Both psychological stress and melatonin affect the immune system, as does the hypothalamus and the autonomic nervous system. The pineal gland has both a direct effect on cancer, and via the immune system. Psychological treatment and melatonin treatment have both been found to alleviate the course of cancer clinically. It is thus hypothesized that the pineal gland, and melatonin, are involved in the mechanism of psychological effects in the promotion of the progress of cancer.

Amygdala↗

Low-grade astrocytomas arising from the pineal gland.

Two cases of low-grade astrocytoma arising from the pineal gland are described in this report. These rare lesions have only been reported on two previous occasions to arise distinctly from the pineal gland. Histologically, one tumor was consistent with a juvenile pilocytic astrocytoma, while the other was consistent with a fibrillary astrocytoma. The pathological features, clinical implications, and treatment of low-grade astrocytomas in the pineal region are discussed.

Adult↗

Fine structural features of adrenergic nerve fibers and endings in the pineal gland of the rat, ground squirrel and chinchilla.

The ultrastructural features of the adrenergic nerve fibers in the pineal glands of the rat, ground squirrel and chinchilla are described. Frequency distribution histograms of diameters of granulated and non-granulated vesicles in the adrenergic nerve endings demonstrate that the pineal nerve endings in the chinchilla contain a considerable number of large granulated and non-granulated vesicles, in contrast to those in the rat and ground squirrel. Synaptic ribbons seen in the pinealocytes of the ground squirrel were often localized near that plasma membrane which lay in close proximity to the axolemma of adrenergic nerve fibers. This observation may indicate that the synaptic ribbons are involved in the functional interconnection between pinealocytes and adrenergic nerve fibers. Localized dilations of the adrenergic nerve fibers were commonly observed in the pineal glands of all species examined. In addition to a variety of axonal constituents, various forms of inclusion bodies were tightly packed within these axonal dilations. The accumulation of the inclusion bodies may represent degenerative changes which occur in the pineal adrenergic nerve fibers in relation to the functional activity of the pineal gland.

Adrenergic Fibers↗

The "third eye"-- a new concept of trans-differentiation of pineal gland into median eye in amphibian tadpoles of Bufo melanostictus.

Median third eye was found to develop from transplanted pineal gland of external gill stage tadpoles in the recipient 5 toe stage tadpoles of Bufo melanostictus. Pineal gland along with a bit part of brain tissue of the donor external gill stage tadpole was cut out and transplanted into a pit made between two lateral eyes of 5 toe stage recipient tadpoles. Half of the operated tadpoles were treated with vitamin A (15 IU/ml.) for 15 days. Median "third eye" was found to develop in the both untreated and vitamin A treated tadpoles. However, vitamin A increased the percentage of the development of median eyes. Morphological and histological study revealed that newly transformed median eyes were similar to that of normal functional eyes. A stalk like structure developed which connects the median eye to the brain. The median third eye could not develop when pineal gland of 5 toe stage mature tadpole was transplanted into the tadpole of the same age.

Animals↗

Pituitary adenylate cyclase-activating polypeptide-immunoreactive (PACAP-IR) nerve fibers in the pig pineal gland.

The present study demonstrates the occurrence of PACAP-immunoreactive (PACAP-IR) nerve fibers in different compartments of the pig pineal gland, including glandular capsule (where they form a very dense network) and subependymal tissue close to the pineal recess (moderate to dense meshwork of varicose fibers). Furthermore, several varicose fibers penetrate from the capsule into the connective tissue septa and then into the parenchyma, where they form unequally distributed, fine network and, in some cases, basket-like structures around pinealocytes. Some of the PACAP-IR nerve fibers, observed both in the habenular and posterior epithalamic areas, extend to the pineal gland. PACAP-IR cells could be demonstrated neither in the pineal gland, nor in epithalamic areas.

Animals↗

Ultrastructural changes in the rat pineal gland after sympathetic denervation. Quantitative study.

Ultrastructural changes in the rat pineal gland were studied quantitatively 7 and 60 days after the sympathetic denervation by bilateral excission or decentralization of superior cervical ganglia. The surface occupied by pineal parenchymal cells decreased in rats of experimental groups with respect to the control group. Furthermore, profile areas of the cytoplasm, nucleus and nucleolus of the pinealocytes were also diminished. Cytoplasmic lipid droplets in the pinealocytes were markedly decreased in number and size in experimental rats. As demonstrated by the Kruskal-Wallis H test, statistically significant differences were found between rats of the control and operated groups. Rats treated by superior cervical ganglionectomy or decentralization showed morphological changes indicating a hypofunctional pineal gland, although differences were found between both groups.

Animals↗

Occurrence and regional distribution of calcareous concretions in the rat pineal gland.

Serial sections of 90 Sprague-Dawley rat brains with the pineal in situ were scanned to determine the occurrence and regional distribution of calcareous concretions within the pineal gland and its surrounding leptomeningeal tissue. In 90% of the cases examined concretions were found in varying number and appearance, predominantly lying in the dorsal region of the pineal gland and in the distal portion of the pineal stalk. Discussing the hypothesis advanced by Lukaszyk and Reiter (1975) that the origin of pineal concretions may be related to a neurosecretory process involving a pineal carrier protein, called neuroepiphysin, it is thought that, in view of the intra- and extra-pineal occurrence of concretions, processes other than secretion should be considered. Since in the pineal organ lymphatics are lacking it may well be that, due to a reduced drainage of tissue fluid, the coagulation of intercellular organic debris mingled with minerals increases with age.

Aging↗

Glial cyst of the pineal gland with characteristic computed tomography, magnetic resonance imaging, and pathological findings: report of two cases.

Two cases of glial cyst of the pineal gland are documented. Preoperative computed tomography and magnetic resonance imaging revealed cystic lesions of the pineal region with contrast enhancement of the walls, suggesting neoplastic lesions rather than true cysts. However, the histopathological examination of the resected specimens revealed the presence of glial tissue and normal structure of pineal gland and capsule, characteristics that were consistent with those of glial cysts of the pineal gland. Headache and visual disturbance were resolved after total removal of the cysts.

Adolescent↗

Evidence for an effect of ELF electromagnetic fields on human pineal gland function.

A study was carried out to determine possible effects of 60-Hz electromagnetic-field exposure on pineal gland function in humans. Overnight excretion of urinary 6-hydroxymelatonin sulfate (6-OHMS), a stable urinary metabolite of the pineal hormone melatonin, was used to assess pineal gland function in 42 volunteers who used standard (conventional) or modified continuous polymer wire (CPW) electric blankets for approximately 8 weeks. Volunteers using conventional electric blankets showed no variations in 6-OHMS excretion as either a group or individuals during the study period. Serving as their own controls, 7 of 28 volunteers using the CPW blankets showed statistically significant changes in their mean nighttime 6-OHMS excretion. The CPW blankets switched on and off approximately twice as often when in service and produced magnetic fields that were 50% stronger than those from the conventional electric blankets. On the basis of these findings, we hypothesize that periodic exposure to pulsed DC or extremely low frequency electric or magnetic fields of sufficient intensity and duration can affect pineal gland function in certain individuals.

Adult↗

Benzodiazepine binding sites in human pineal gland.

The high affinity binding of [3H]flunitrazepam (FNZP) to crude membrane preparations was examined in human pineal glands. Scatchard analysis of the data at equilibrium revealed a single population of binding sites with dissociation constant = 2.36-2.53 nM and binding site concentration = 59-108 fmol/mg protein. When various benzodiazepine (BZP) analogues were tested for their ability to inhibit [3H]FNZP binding the following Ki (nM) were found: clonazepam (0.13), RO 15-1788 (0.60), FNZP (2.14), diazepam (13.5), Ro 5-4864 (greater than 10 000). In both human pineal gland and cerebral cortex 10-100 microM gamma-aminobutyric acid (GABA) increased BZP binding by about 30%, an effect inhibited by the GABA receptor blocker bicuculline. The stimulatory effect of GABA on [3H]FNZP binding in rat cerebral cortex (about 60%) decreased as a function of time elapsed postmortem at room temperature to reach values similar to those observed in human brains. These results suggest the existence of central type BZP receptors in the human pineal glands.

Adolescent↗

The pineal gland and the clinical course of multiple sclerosis.

Clinical, epidemiological, biochemical, immunological, and radiological studies suggest that the pineal gland may be implicated in the pathophysiology of multiple sclerosis (MS). The following communication is concerned with the association among MS, pregnancy, the postpartum period, and melatonin secretion and illustrates, based on a clinical case report, the influence of the pineal gland on the clinical course of MS. This association is noteworthy since MS may worsen during the postpartum period and melatonin secretion is reported to be altered most dramatically by pregnancy and delivery. Since melatonin secretion is cyclical, undergoing diurnal, weekly, seasonal, and annual variations, it is proposed that the pineal gland may be the "prime mover" underlying the spontaneous exacerbations and remissions in MS.

Calcinosis↗

Regulation of synaptic ribbons in rat pineal gland explants by norepinephrine and sympathetic neurons in a co-culture model.

The hypothesis that synaptic ribbons in the mammalian pinealocyte are influenced by adrenergic mechanisms was tested in the present study using a co-culture model of pineal glands and superior cervical ganglia from neonatal rats. Pineal gland explants survived and showed a high degree of differentiation when cultured for up to 30 days regardless of the presence or absence of superior cervical ganglia. Pineal glands also had neurotrophic properties promoting the survival and neurite extension from superior cervical ganglia. Synaptic ribbons were a common ultrastructural feature in all pineal cultures. There was a significant decline in synaptic ribbon numbers when co-cultured with superior cervical ganglia for both 7 and 30 days. A similar significant decrease in synaptic ribbon frequency was observed after treatment of pineal explants with norepinephrine (10(-5 )M) for both 7 and 30 days. These findings are consistent with the hypothesis that neural mechanisms play an important role in regulating synaptic ribbon numbers, at least during early development. The study also illustrates the utility of pineal gland-superior cervical ganglia co-cultures as a model for future investigations of neuron-target interactions in the pineal.

Animals↗

Neural connections between the brain and the pineal gland of the golden hamster (Mesocricetus auratus). Tracer studies by use of horseradish peroxidase in vivo and in vitro.

Neurons projecting from the brain to the pineal gland via the pineal stalk were investigated in the golden hamster with the use of the retrograde horseradish-peroxidase tracing method both in vivo and in vitro. Labelled perikarya were observed in the medial and lateral habenular nuclei as well as in the posterior commissure. Single cells located in the ependymal lining of the pineal- and suprapineal recesses were also retrogradely labelled. These results show that a distinct central innervation of the pineal gland exists in the golden hamster, in agreement with findings in other mammalian species investigated by means of a similar methodology. In addition, also direct signals from the cerebrospinal fluid to the parenchyma might be conducted via cells located within the ependymal layer of the pineal- and suprapineal recesses.

Animals↗

The human pineal gland in aging and Alzheimer's disease: patterns of cytoskeletal antigen immunoreactivity.

Patients with Alzheimer's disease (AD) and some aged controls may have diminished functions of the pineal gland. In this immunocytochemical study, we stained pineal glands from cases of AD and young and aged controls for cytoskeletal elements and amyloid. We found no evidence of neurofibrillary tangles (NFT) or the accumulation of neurofilaments, tau, A68, or beta/A4 amyloid deposition in pinealocytes or associated structures in cases of AD or controls. In both AD and controls, we observed dense immunoreactivity for phosphorylated neurofilaments in marginal plexuses associated with processes of pinealocytes, boutons, and knob-like endings. The accumulation of phosphorylated neurofilaments in the processes of pinealocytes appears to be a normal morphological characteristic of the pineal gland and may not represent a pathological change.

Adolescent↗

Is the vasoactive intestinal peptide-like immunoreactivity in the rat pineal gland present in fibers originating in the superior cervical ganglion?

Serotonin N-acetyltransferase is regulated in the rat pineal gland by the gland's innervation from the superior cervical ganglion. Norepinephrine has been viewed as the sole transmitter involved in this trans-synaptic regulation; however, a possible role for vasoactive intestinal peptide (VIP) has recently emerged. VIP-like immunoreactivity was extracted from rat pineal glands and shown to co-elute on reverse-phase liquid chromatography with authentic VIP. The level of VIP-like immunoreactivity in the gland was unaffected by prior sympathetic denervation, though its level of neuropeptide Y-like immunoreactivity decreased by 85%. The results indicate that VIP and norepinephrine are not colocalized in sympathetic neurons in the pineal gland and raise questions as to the physiological role of VIP in regulation of pineal function in vivo.

Animals↗

An immunohistochemical study on the postnatal changes in the C-terminal flanking peptide of neuropeptide Y (CPON)--positive nerve fibers in pineal gland of the pig.

Postnatal development of innervation of the porcine pineal gland by C-terminal flanking peptide of neuropeptide Y (CPON)-immunoreactive nerve fibers was examined using the immunohistochemical technique. CPON-positive nerve fibers appeared in the pineal gland of the new-born piglets and formed plexus in the capsula and connective tissue septa of the gland. The nerve terminals branched off from the plexus and penetrated into adjacent parenchyma. The number of nerve fibers immunoreactive to CPON in parenchyma is very low in new-born and 20-day-old piglets. In 7-month-old pigs they created a dense network.

Adrenergic Fibers↗