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Vipergic innervation of the mammalian pineal gland.

The present article reviews the literature relative to VIP- and PHI-containing nerve fibers in the pineal gland of mammals. The article summarizes data on the presence and distribution of the two peptides in the brain of mammals, their role in neuronal metabolism, and the significance and origin of VIPergic and PHIergic cerebrovascular nerve fibers. Special emphasis is placed on VIP- and PHI-containing nerves in the pineal gland. The morphology of the fibers, the nature of the innervation, and the distribution of immunoreactive nerves within the pineal gland are examined. The review discusses the nature of the classical and "central" innervation of the pineal gland. The possible site of origin of pinealopetal VIPergic and PHIergic fibers is investigated, with special reference to ganglia of the head, and particularly to the pterygopalatine, otic, and trigeminal ganglia. The nature of VIP (and PHI) receptors is examined with reference to the most recent acquisitions in the field. Based on the data, a role for VIP (and PHI) in pineal metabolism is discussed.

Amino Acid Sequence↗

The pineal gland of the red deer male. Histology and ultrastructure with notes on the fallow deer and mouflon pineals.

The most conspicuous morphological feature of the investigated red deer pineal gland was very deep pineal recess, covered with continuous layer of the ependymal cells. Its branches (2-3) reached the distal part of the gland. The slight differences in pineal structure of sexually active and sexually inactive red deer were observed. Relatively large pineal glands both of mouflon and fallow deer showed many common as well as different structural features.

Animals↗

Indications for a central innervation of the bovine pineal gland with substance P-immunoreactive nerve fibers.

An antiserum, raised in rabbits, against substance P was used in an immunohistochemical investigation of the bovine pineal gland. A moderate innervation of all parts of the bovine pineal gland with substance P-immunoreactive nerve fibers was demonstrated. The immunoreactive nerve fibers were located throughout the pineal gland, both perivascularly, intraparenchymally, and with few fibers in the pineal capsule. Within the habenular nucleus, a large number of substance substance P-immunoreactive perikarya were present. From these perikarya processes extended towards the pineal stalk and gland. Some substance P-immunoreactive nerve fibers were located in the stria medullaris and in the posterior commissure. The anatomical location of the substance P-immunoreactive nerve fibers in the pineal gland and stalk strongly indicates that, in this species, substance P-immunoreactive pinealopetal nerve fibers originate from perikarya in the brain, probably from the medial habenular nucleus.

Animals↗

[Circadian rhythms of pineal gland melatonin-forming function in healthy elderly people].

Circadian rhythms of pineal gland melatonin-forming function were studied in healthy elderly people (n=31, age range 60-74 years). The blood plasma melatonin concentration was determined by means of radioimmune method at 3.00, 9.00, 15.00 and 21.00. The study revealed two types of circadian rhythms of plasma melatonin concentration: a high-amplitude (29%) and a low-amplitude (71%) ones. The high-amplitude rhythm of melatonin-forming pineal gland function was observed in elderly people with a higher physical working ability and a lower functional age of cardiovascular system. It is advisable to conduct the correction of pineal gland melatonin-forming function in elderly people with low-amplitude circadian rhythm of plasma melatonin concentration.

Aged↗

Functional connections between the pineal gland and immune system.

Experimental findings which support a functional connection between the pineal gland and immune system in mammals and birds are summarized. Developmental and age-related changes in pineal gland function appear, at least partially, to be related with immune system efficiency. Mechanisms whereby melatonin influences immune system function are complex, but include participation of mediators (endogenous opioids, cytokines, hormones, zinc pool) as well as specific binding sites on the immune cells. Melatonin, as a highly lyophilic compound, may also penetrate immune cells without mediation of specific receptors and act within as a potent free radical scavenger and as an anti-aging and oncostatic factor. The immune system may, in turn, via synthesis and secretion of soluble factors, cytokines, influence pineal gland function, thereby closing the information loop to maintain homeostasis in order to face the harmful environment.

Animals↗

Pretranslational regulation of rhythmic type II iodothyronine deiodinase expression by beta-adrenergic mechanism in the rat pineal gland.

It has been demonstrated that type II iodothyronine deiodinase is present in rat pineal gland, and the deiodinase activity markedly increases during the hours of darkness, primarily through beta-adrenergic mechanism. We have studied the relationship between pineal type II iodothyronine deiodinase messenger RNA (mRNA) and the deiodinase activity to elucidate the mechanisms involved in the nocturnal rise in pineal deiodinase activity. Northern analysis has demonstrated that type II iodothyronine deiodinase mRNA is expressed in rat pineal gland, and the mRNA markedly increases during the hours of darkness. The nocturnal increase in pineal type II iodothyronine deiodinase activity is preceded by the increase in its mRNA. Daytime isoproterenol administration resulted in a rapid increase in pineal type II iodothyronine deiodinase mRNA followed by the increase in deiodinase activity. Propranolol treatment, bilateral superior cervical ganglionectomy, or constant light exposure significantly suppressed the nocturnal rise in type II iodothyronine deiodinase mRNA as well as the deiodinase activity. Moreover, isoproterenol or (Bu)2AMP stimulated type II iodothyronine deiodinase mRNA and the deiodinase activity in cultured rat pineal glands. These results suggest that the rhythmic change in pineal type II iodothyronine deiodinase activity is regulated at least in part at the pretranslational level by a beta-adrenergic mechanism transmitted through superior cervical ganglia.

Adrenergic beta-Agonists↗

Endothelin-1 stimulates phosphoinositide hydrolysis in the rat pineal gland.

The presence of functional endothelin receptors and their signal transduction mechanism has not been determined so far in the pineal gland. We examined the effect of endothelin-1 (ET-1) on phosphoinositide turnover in whole pineal gland. Endothelin-1 increased monophosphate accumulation in a dose-dependent manner. The phosphoinositide (PI) response elicited by ET-1 was dependent on the presence of extracellular Ca (++) since its chelation resulted in a marked decrease in ET-1-stimulated InsP(1) accumulation. On the contrary, phosphoinositide hydrolysis was not changed by the calcium blocker amlodipine. ET-1 induced PI breakdown was inhibited by neomycin, an inhibitor of phospholipase C. However, mastoparan 7, a G protein activator via Gi/Go s timulation, did not alter ET-1-induced InsP(1) accumulation. Our data indicate that stimulation of PI turnover constitutes one of the signaling pathways of ET in rat pineal gland through the stimulation of a receptor-coupled phospholipase C. And they demonstrate, for the first time, the presence of functional binding sites for endothelin in the pineal gland.

Amlodipine↗

A direct influence of moonlight intensity on changes in melatonin production by cultured pineal glands of the golden rabbitfish, Siganus guttatus.

Rabbitfish are a restricted lunar-synchronized spawner that spawns around a species-specific lunar phase. It is not known how the fish perceive changes in cues from the moon. One possible explanation is that rabbitfish utilize changes in moonlight intensity to establish synchrony. The purpose of the present study was to examine whether or not the pineal gland of the golden rabbitfish can directly perceive changes in moonlight intensity. Isolated pineal glands were statically cultured under natural or artificial light conditions and melatonin secreted into the culture medium was measured using a time-resolved fluoroimmunoassay. Under an artificial light/dark cycle, melatonin secretion significantly increased during the dark phase. Under continuous light conditions, melatonin secretion was suppressed, while culture under continuous dark conditions seemed to duplicate melatonin secretion corresponding to the light/dark cycle in which the fish were acclimated. When cultured pineal glands were kept under natural light conditions on the dates of the full and the new moon, small amounts of melatonin were secreted at night. Moreover, exposure of cultured pineal glands to artificial and natural light conditions resulted in a significant decrease of melatonin secretion within 2 hr. These results suggest that the isolated pineal gland of golden rabbitfish responds to environmental light cycles and that 'brightness' of the night moon has an influence on melatonin secretion from the isolated pineal gland.

Animals↗

Structure and ultrastructure of the pigmented cells in the adult dog pineal gland.

The light and electron microscopic features of pigmented cells in the adult dog pineal gland have been described. The presence of pigmented cells was a constant characteristic of the dog pineal gland, though wide variations in the amount of pigment could be found among different animals. Conversely, the localisation of pigmented cells was very constant on the basal surface of the proximal region of the pineal gland. Frequently, clusters of pigmented cells were seen in the posterior commissure and the neighbour meningeal spaces, near the pigmented pineal zone. The pineal pigment has been identified as melanin according to its morphological features and histochemical properties. Several types of granules were identified ultrastructurally, apparently corresponding to different stages of a maturation process. The pigmented cells were identified as a special type of pinealocyte according to their ultrastructural features.

Animals↗

Effect of artificial and human external qigong on electroencephalograms in rabbit and spontaneous electrical activity of the rat pineal gland.

External gigong emitted by a quartz crystal upon application of electric current was evaluated by its biological effects, such as changes in frequency-analyzed electroencephalograms (EEG) in rabbits and spontaneous electrical activity of the rat pineal gland. Physical properties of this external gigong cannot be evaluated by currently available physical means. Three types of EEG changes were produced depending on the intensity of current applied to the crystal. These changes corresponded fairly well to the dose-dependent EEG changes after intravenous administration of 5-hydroxytryptophan. A gigong-containing medal also produced similar EEG changes depending on threshold to gigong. Human gigong similarly influenced EEG. All EEG changes disappeared after pinealectomy or after application of methysergide (10 mg/kg), a serotonin antagonist. The rate of spontaneous electrical activity of the pineal gland was depressed by reorientation of the rat to the north or to the south, by gigong emitted by a quartz crystal, or by application of a gigong-containing medal. Human gigong also depressed this electrical activity. The EEG changes produced by external gigong might be caused by increased serotonin concentration in the pineal gland, since the pineal gland is responsive to gigong as well as the earth's magnetic field, which is known to inhibit N-acetyltransferase by increasing serotonin concentration in the pineal gland. Hence, the finding that current-intensity-dependent EEG changes induced by quartz crystal-emitted gigong were analogous to dose-dependent EEG changes produced by 5-hydroxytryptophan might be attributed to increased serotonin levels by current-intensity-dependent inhibition of N-acetyltransferase by external gigong.

5-Hydroxytryptophan↗

Differential expression and enzymatic properties of the Na+,K(+)-ATPase alpha 3 isoenzyme in rat pineal glands.

We have used immunoblotting and biochemical techniques to analyze expression of Na+,K(+)-ATPase alpha and beta subunits in rat pineal glands. Western blot analysis of pineal microsomal membrane fractions with antisera specific for each of the three rat alpha and two rat beta subunits revealed similar levels of expression of alpha 1 and alpha 3 subunits in pineal glands of 5-day-old rats. High levels of alpha 3 and beta 2 subunits and low levels of alpha 1 subunits were detected in adult glands. No alpha 2 or beta 1 subunits were detectable at either developmental stage. Examination of the enzymatic properties of the pineal gland alpha 3 isoform suggests that this enzyme is a ouabain-sensitive ATPase whose activity is dependent upon Na+ and K+. This ATPase exhibited a lower apparent Km for Na+ than the kidney alpha 1 isoenzyme and did not show positive cooperative Na+ activation. Our results suggest that the activity of the Na+,K(+)-ATPase alpha 3 isoenzyme may be adapted to function under conditions of hyperpolarizing transmembrane potentials.

Aging↗

Effect of psychotropic drugs on the contents of melatonin, serotonin and N-acetylserotonin in rat pineal gland.

In the dark phase, the effects of the psychotropic drugs on the contents of melatonin, serotonin (5-HT) and N-acetylserotonin (NAS) in rat pineal gland were examined. The pineal gland was removed at a certain period of time after subcutaneous injection of the drugs. 5-HT, NAS and melatonin contents in the pineal gland were determined by high performance liquid chromatography with fluorometric detection. A dose-dependent decrease was observed for melatonin content in the administration of diazepam (DZP), hydroxyzine (HYZ), chlorpromazine (CPZ) or haloperidol (HPD). When imipramine (IPM) or amitriptyline (APL) was given to rats, pineal 5-HT content was significantly decreased. On the other hand, the administration of IPM or APL caused increases in pineal NAS and melatonin. Furthermore, the administration of phenytoin (PYT) revealed no changes in the content of pineal indoleamines. These results suggest that the psychotropic drugs widely used in clinical applications could cause significant changes in pineal indoleamine content.

Animals↗

Modulation of ganglion cell activity in the pineal gland of the rainbow trout: effects of cholinergic, catecholaminergic, and GABAergic receptor agonists.

Second order neurons within intact isolated pineal glands of the rainbow trout were explored by extracellular recordings to investigate modulatory effects of putative intrapineal neurotransmitters. Acetylcholine, dopamine, and norepinephrine were found to increase ganglion cell activity in a majority of cells tested. The excitatory effects of acetylcholine, dopamine, and norepinephrine were mimicked by muscarinic, dopamine D2, and beta-adrenergic receptor agonists and significantly increased with the applied light intensity, resulting in an attenuation of the ganglion cell response to light. GABA decreased discharge activity in most cells tested. This effect, which could be mimicked with the GABAA receptor agonist piperidine, was independent from the adaptive status. Acetylcholine and GABA were still active if applied during synaptic blockade with low Ca++ high Mg(++)-perfusion medium, whereas dopamine and norepinephrine exhibited no effects if applied during synaptic blockade, suggesting a differential cellular distribution of neurotransmitter receptors in the trout pineal gland. These data demonstrate that ganglion cell activity in the trout pineal gland is under the influence of several neurotransmitters, including acetylcholine, dopamine, norepinephrine, and GABA, which is in contrast to the originally proposed simple bineuronal transduction pathway from photoreceptors onto ganglion cells. Since the above-mentioned neurotransmitters are believed to be released from pineal interneurons, we may conclude that ganglion cell activity in the teleost pineal gland is, similarly to the retina, the product of photoreceptor signals and a modulatory active interneuronal system.

Action Potentials↗

Localization and diurnal expression of mRNA encoding the beta1-adrenoceptor in the rat pineal gland: an in situ hybridization study.

The rat pinealocyte is stimulated by norepinephrine, which is released from sympathetic nerve fibers innervating the gland. Norepinephrine binds to beta1-adrenoceptors situated on the pinealocyte cell membrane. Ligand binding to these receptors exhibits a diurnal rhythm, with the largest number occurring in the late part of the light phase when the release of norepinephrine is minimal. By using in situ hybridization with a cDNA antisense oligonucleotide probe recognizing mRNA encoding the rat beta1-adrenoceptor, we have demonstrated a stronger hybridization signal in the rat pineal gland than in other brain regions. Cells containing beta1-mRNA are located in the superficial pineal gland, the deep pineal gland, and the pineal stalk. However, the number of receptors varies considerably between the individual pinealocytes. The beta1-mRNA in situ hybridization signal for mRNA encoding the beta1-adrenoceptor of the rat pineal has been quantified over a 24-h period; the strongest signal is found at mid-dark and the weakest signal at mid-light, indicating that the transcriptional regulation of beta1-mRNA synthesis in the rat pineal is diurnal. In addition, maximal receptor protein expression occurs late in the light phase in the rat pineal and is thus considerably delayed compared with its peak mRNA synthesis. This lag time indicates that the beta1-receptor is regulated at the translational or post-translational level. Removal of the sympathetic input to the pineal gland by superior cervical ganglionectomy decreases the beta1-mRNA signal in the gland.

Animals↗

Daily oscillation in melatonin synthesis in the Turkey pineal gland and retina: diurnal and circadian rhythms.

The aim of the present study was to examine arylalkylamine N-acetyltransferase (AANAT) activity and melatonin content in the pineal gland and retina as well as the melatonin concentration in plasma of the turkey (Meleagris gallopavo), an avian species in which several physiological processes, including reproduction, are controlled by day length. In order to investigate whether the analyzed parameters display diurnal or circadian rhythmicity, we measured these variables in tissues isolated at regular time intervals from birds kept either under a regular light-dark (LD) cycle or under constant darkness (DD). The pineal gland and retina of the turkey rhythmically produced melatonin. In birds kept under a daily LD cycle, melatonin levels in the pineal gland and retina were high during the dark phase and low during the light phase. Rhythmic oscillations in melatonin, with high night-time concentrations, were also found in the plasma. The pineal and retinal melatonin rhythms mirrored oscillations in the activity of AANAT, the penultimate enzyme in the melatonin biosynthetic pathway. Rhythmic oscillations in AANAT activity in the turkey pineal gland and retina were circadian in nature, as they persisted under conditions of constant darkness (DD). Transferring birds from LD into DD, however, resulted in a potent decline in the amplitude of the AANAT rhythm from the first day of DD. On the sixth day of DD, pineal AANAT activity was still markedly higher during the subjective dark than during the subjective light phase; whereas, AANAT activity in the retina did not exhibit significant oscillations. The results indicate that melatonin rhythmicity in the turkey pineal gland and retina is regulated both by light and the endogenous circadian clock. The findings suggest that environmental light may be of primary importance in the maintenance of the high-amplitude melatonin rhythms in the turkey.

Animals↗

Pineal gland abnormalities in Langerhans cell histiocytosis.

BACKGROUND: The most common types of central nervous system (CNS) disease in Langerhans cell histiocytosis (LCH) comprise involvement of the hypothalamic-pituitary region (HPR) and neurodegenerative changes in the cerebellum, basal ganglia or pons. In the review process of magnetic resonance images (MRI) from 129 LCH patients a high frequency of cysts within or large pineal glands was noted by chance. PROCEDURE: To prove whether this observation was specific for LCH or not, we compared MRI findings of the HPR in LCH patients with a control group of 55 non-LCH patients with the same age and sex distribution. RESULTS: In LCH patients, the pineal gland was significantly larger and also the number of pineal cysts was significantly higher as compared to the control group. No difference was found regarding the size or frequency of cystic changes between patients who had received chemotherapy prior to the MRI and untreated patients. In the LCH patients, we further found a significant correlation of pineal gland enlargement with involvement of the HPR, but not with neurodegenerative changes. Analysis of melatonin (the principal hormone of the pineal gland) levels in 24 hr urine in 14 LCH patients did not reveal a melatonin deficiency or overproduction in the LCH group as compared to 6 normal controls. CONCLUSIONS: The pineal gland is another site of possible CNS involvement in LCH. LCH CNS patients did not show an overt disturbance in melatonin levels. The role of the pineal gland in CNS LCH remains to be defined.

Adolescent↗

Sympathetic nerve endings in the pineal gland protect against acute stress-induced increase in N-acetyltransferase (EC 2.3.1.5.) activity.

Injection of the antidepressant desmyethylimipramine (DMI, 10 mg/kg) into intact rats or into rats in which the superior cervical ganglia had been decentralized caused a marked enhancement of the swimming stress-induced increase in pineal gland acetyl-CoA:serotonin N-acetyltransferase (N-acetyltransferase, EC 2.3.1.5) activity. DMI is known to block uptake, the transport of catecholamines by nerve endings. It was found that DMI had no effect on enzyme activity in superior cervical ganglionectomized (SCGX) rats which were swimming stressed. The pineal glands of these animals are devoid of nerve endings. In unstressed intact or unstressed surgically altered rats, injection of DMI caused only a minor increase in N-acetyltransferase activity, which was much smaller than that seen after stress. After 5 h in organ culture sympathetic nerve endings within the pineal gland are still intact. At this time DMI treatment of pineal glands taken from intact rats shifted the dose-response curve for epinephrine (EPI) stimulation of N-acetyltransferase activity by two orders of magnitude, but caused only a slight change in the dose-response curve for isoproterenol, which is not taken up into nerve endings. In contrast, DMI treatment in organ culture had no effect on the dose-response curve for EPI in denervated pineal glands. These results support the hypothesis that the response of pineal N-acetyltransferase activity to stimulation by stress is influenced by uptake. It would appear that in addition to terminating neuronal adrenergic transmission, this transport process physiologically protects the pineal gland against nontranssynaptic adrenergic stimulation.

Acetyltransferases↗