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[Magnetic resonance study of the pineal region. Normal pineal gland and simple cysts].

A magnetic resonance imaging (MRI) study of the normal pineal gland and pineal simple cysts was performed in 762 cases. A fine section technique (maximum 3 millimeters) enabled most of the times the identifying of a normal pineal in addition to demonstrating that a pineal without any cyst shows an isointense signal in T1 and T2 which, in turn, is enhanced following gadolinium. The measure of the normal pineal was of about 6.1 millimeters in its diameter length. Pineal simple cysts were observed in a 2.6% frequency in relation to the whole series (762 cases); however reaches 6.1% when only the visualized pineals were considered (329 cases). Also, it was found out that simple cysts were not correlated to age or gender. Simple cysts characteristics are: dimension less or equal to 20 millimeters; absence of expansive effect; similar signal to that of the cerebrospinal fluid; absence of cyst growth.

Adolescent↗

Thyroxine 5'-deiodinase activity in pineal gland and frontal cortex: nighttime increase and the effect of either continuous light exposure or superior cervical ganglionectomy.

Type II T4 5'-deiodinase (5'-D) activity was studied in pineal gland, frontal cortex, and anterior pituitary of male rats. Enzymatic activity was determined by the release of 125I using [3',5'-125I]T4 as substrate. Daytime levels of 5'-D activity were maximal for anterior pituitary (346.2 +/- 142.5 fmol 125I released/mg protein.h), followed by pineal gland (61.5 +/- 8.7 fmol 125I released/mg protein.h) and frontal cortex (3.1 +/- 0.5 fmol 125I released/mg protein.h). Twenty-four-hour fluctuations of 5'-D activity were apparent in the pineal gland and cortex. For pineal, peak 5'-D activity (43.4 +/- 11.4 fmol 125I released/gland.h) occurred at 0100 h, with values at this time being 8-fold greater than basal daytime levels. Superior cervical ganglionectomy (SCGX) or exposure to continuous light (LL) completely abolished the nocturnal rise of 5'-D activity. Treatment with iopanoic acid also inhibited 5'-D activity in pineal (32.1 +/- 3.5 vs. 18.8 +/- 1.7 fmol 125I released/gland.h) without influencing either the N-acetyltransferase activity or the melatonin content. In cortex, peak 5'-D activity occurred at 0500 h (5.3 +/- 0.4 fmol 125I released/mg protein.h), with values at this time being 1.5-fold greater than basal daytime levels. SCGX moderately depressed enzymatic activity, while LL exposure strikingly enhanced the nocturnal increase (11.7 +/- 1.1 vs. 19.3 +/- 2.4 fmol 125I released/mg protein.h at 0300 h). 5'-D activity exhibited no 24-h fluctuation in the anterior pituitary gland, and neither SCGX nor LL exposure affected enzyme levels in this tissue. Our data demonstrate the existence of a 24-h rhythm of type II T4 5'-D activity in pineal gland and cortex, with peak levels occurring at night; in pineal, the sympathetic neural input is indispensable for the rhythm, since SCGX prevented it. In cortex, the apparent paradoxical effect of LL and SCGX on 5'-D activity indicates that other mechanisms are involved in its regulation.

Animals↗

Interstitial and parenchymal cells in the pineal gland of the golden hamster. A combined thin-section, freeze-fracture and immunofluorescence study.

A combined thin-section/freeze-fracture study was performed on the superficial pineal gland of the golden hamster, comparing the parenchymal and interstitial cells of this animal with those previously investigated in rats. In contrast to rats, no gap junctions and gap/tight junction combinations could be found between pineal parenchymal cells of the hamster. Furthermore, the interstitial cells of the hamster pineal gland were found to have large flat cytoplasmic processes, which abut over large areas equipped with tight junctions. In thin sections, profiles of interstitial cell processes were seen to surround groups of pinealocytes. Interstitial cells and their sheet-like, tight junction-sealed processes thus appear to delimit lobule-like compartments of the hamster pineal gland. Because the classification of the interstitial cells uncertain, the expression of several markers characteristic of mature and immature astrocytes and astrocyte subpopulations has been investigated by indirect immunohistology. Many of the non-neuronal elements in the pineal gland are vimentin-positive glial cells, subpopulations of which express glial fibrillary acidic protein (GFA) and C1 antigen. The astroglial character of these cells is supported by the lack of expression of markers for neuronal, meningeal and endothelial cells. M1 antigen-positive cells have not been detected.

Animals↗

Nitric oxide inhibits electrically active units in the rat pineal gland.

Extracellular multiple unit recordings were performed in isolated rat pineal glands to determine a possible effect of nitric oxide (NO) on the spontaneous electrical activity of pinealocytes. Spontaneously active cells forming clusters of 3-5 cells fell into two categories: more or less regularly firing clusters (REG, 64%) and irregularly discharging clusters with periodically repeated bursts (RHY, 36%). The NO-donor sodium nitroprusside (SNP) reduced the discharge rate of the great majority of REG clusters and of all the RHY clusters examined. Moreover, the burst activity of RHY clusters was abolished. These results could be completely reproduced by using another NO-donor, S-nitroso-N-acetyl-penicillamine (SNAP). The NO synthase inhibitor NMLA had no effect on REG and RHY clusters. The results show that spontaneous electrical activity is an intrinsic function of the rat pineal gland. NO can modulate the electrical activity affecting discharge rate and discharge pattern.

Animals↗

Circadian and photic regulation of cryptochrome mRNAs in the rat pineal gland.

Expressions of Cry1 and Cry2 mRNA in the rat pineal gland were examined by Northern blot. The levels of Cry1 and Cry2 transcript had a marked circadian rhythm with peaks at circadian time (CT) 20 in constant darkness. But the amplitude of the Cry1 rhythm was higher than that of the Cry2 rhythm. Furthermore, a significant increase in Cry1 mRNA levels was caused by light pulse given at CT 16 but not at CT 4, but the expression of Cry2 was not significantly induced by light pulses given at either CT 4 or CT 16. These results suggest that Cry1 in the pineal gland is regulated by photic and circadian information but Cry2 is only regulated by circadian information.

Animals↗

Descartes and the pineal gland in animals: a frequent misinterpretation.

René Descartes presented a number of reasons for his choice of the pineal gland as a logical place for the soul to interact with the physical machinery of the body. It is often stated that one of his reasons was that he believed animals do not have pineal glands, whereas humans alone possess a soul and this small structure. This is a misinterpretation of Descartes. The philosopher knew that barnyard and other animals possess pineal glands, having seen this with his own eyes. His point was that the pineal is unique in humans only because of a special function - acting as the seat for the rational soul.

Animal Population Groups↗

24-Hour changes in catecholamine synthesis in rat and hamster pineal glands.

The purpose of this study was to examine the 24-hour variation in endogenous tyrosine hydroxylase (TH) activity and thus catecholamine (CA) synthesis in the hamster and rat pineal gland. To determine CA synthesis a time course of the accumulation of dihydroxyphenylalanine (DOPA) after DOPA decarboxylase inhibition with m-hydroxybenzylhydrazine (NSD-1015) was measured at 0, 15 and 30 min by liquid chromatography with electrochemical detection. Animals were under long photoperiods (LD 14:10; lights on at 06.00 h). In the hamster pineal gland, CA synthesis was greater in the dark (24.00 h) (0.017 ng/pineal/min) than in the light (12.00 h) (0.008 ng/pineal/min). Similarly, CA synthesis in the rat pineal was 0.037 ng/pineal/min (dark) and 0.005 ng/pineal/min (light). In a 24-hour study, animals were injected with NSD-1015,30 min prior to killing to determine if 24-hour changes were present in CA synthesis. In the hamster, DOPA in the dark (p less than 0.001) was significantly greater than in the light (1.33 +/- 0.42 ng/pineal at 06.00 h; 0.33 +/- 0.07 at 13.00 h) in this study. No significant difference was measured in norepinephrine (NE) concentration during this 24-hour period. In the rat, DOPA accumulation was significantly different (p less than 0.001) in the dark as compared to the light (0.86 +/- 0.09 ng/pineal at 03.00 h; 0.21 +/- 0.08 at 12.30 h). Within this 24-hour period, NE concentration fluctuated significantly between 2.28 +/- 0.33 ng/pineal (15.30 h) to 4.65 +/- 0.59 (05.30 h). These results indicate for the first time a definite 24-hour rhythm in endogenous TH activity and NE synthesis in the hamster pineal gland even though NE content does not change. In addition, a 24-hour change in CA synthesis and content is present in the rat pineal gland.

Animals↗

Day- and nighttime content of monoamines and their metabolites in the pineal gland of rat and hamster.

Day- and nighttime content of catecholamines, serotonin and their metabolites were measured in the pineal gland of Sprague-Dawley rats and Djungarian hamsters. In addition, monoamine turnover rates were determined in the hamster pineal gland following administration of alpha-methyl-p-tyrosine. Animals were decapitated in the middle of the light or dark period, respectively, and pineal tissue was analysed by high performance liquid chromatography with electrochemical detection. Pineals of both species exhibited day/night-differences in serotonin, 5-hydroxyindole-3-acetic acid and dopamine content. The hamster pineal gland further showed day/night differences in its content of epinephrine and 3-methoxy-4-hydroxyphenylethyleneglycol. The dopamine turnover rate was augmented at night, while norepinephrine turnover was constant. Immunohistochemical incubations of pineal paraffine sections showed fibers and terminals stained by antisera to tyrosine-hydroxylase (TH) and dopamine-beta-hydroxylase, and a few perikarya-like structures exhibiting TH immunoreactivity. The results support the view that dopamine, rather than only functioning as a norepinephrine precursor, is actively involved in the control of melatonin synthesis.

Animals↗

Maternal coordination of the daily rhythm of malate dehydrogenase activity in testes from young rats: effect of maternal sympathetic denervation of the pineal gland and administration of melatonin.

Chronic sympathetic denervation of the pineal gland by bilateral removal of the superior cervical ganglia (SCG) was performed on female rats 30 days before impregnation. The offspring, maintained in the dark from birth, had disruption of the malate dehydrogenase circadian rhythm in the testes at 25 days of age. A daily injection of melatonin (1 mg/kg s.c. at 10:00 or 18:00 h) to denervated mothers from the 14th day of pregnancy up to the 10th day postpartum produced one daily phase in the enzyme activity of tests in the offspring. Entrainment of daily enzyme activity also was obtained when the hormone was administered orally to the pups during the postnatal period or when pups were reared by intact (not denervated) foster mothers. The results indicate the involvement of the maternal pineal gland in the maternal transfer of photoperiodic information necessary for the coordination of the circadian system in young rats.

Adrenergic Fibers↗

Norepinephrine stimulates serotonin secretion from rat pineal glands, in vitro.

The purpose of this study was to determine if serotonin (5-HT) is secreted by the pineal gland and also to define the parameters of its secretion. After radiolabelling the endogenous 5-HT pool, individual pineal glands were placed within perifusion chambers and stimulated with norepinephrine (NE). [3H]5-HT was rapidly released within 1 min of stimulation and secretion continued throughout the period of exposure to NE. The findings suggest that 5-HT, in addition to melatonin, is a hormone of the pineal gland.

Animals↗

Predominant cytosolic distribution of serotonin in rat pineal gland in contrast to biogenic monoamine localization in midbrain and adrenal gland.

The subcellular distribution of serotonin and norepinephrine in the rat pineal gland was studied by tissue fractionation and compared with that of biogenic monoamines in the adrenal gland and midbrain. Homogenized tissues were fractionated by ultracentrifugation or by filtration through cellulose ester membranes. Most of the epinephrine (70-80%) and norepinephrine (62-82%) present in the adrenal glands was detected in the particulate fraction. The same distribution was found for serotonin (68.5%) and norepinephrine (59%) in the midbrain and for norepinephrine (62.5%) in the pineal gland. However, most of the serotonin in the pineal was found in the soluble fraction (89.5-98%). This suggests that the great majority of serotonin in the rat pinealocytes is cytosolic and thus is not stored in subcellular vesicles, in contrast to the biogenic monoamines in the midbrain or adrenal gland.

Adrenal Glands↗

Postnatal appearance of luteinizing hormone-releasing hormone (LHRH)-like material in the pineal gland of the rat.

Immunoreactive luteinizing hormone-releasing hormone (LHRH)-like material has been demonstrated in the pineal gland of the adult rat. The objective of the present study was to examine the ontogenetic development of this LHRH-like substance in the rat pineal with the peroxidase-antiperoxidase (PAP) method of Sternberger. LHRH-like immunoreactive material was not observed in pineal glands of newborn rats. The amount of material increased progressively from the 6th-12th day of postnatal development. On day 12, the amount of LHRH-like immunoreactivity was consistent and comparable in all pineal glands of male and female animals examined.

Animals↗

Macrophages/microglia as 'sensors' of injury in the pineal gland of rats following a non-penetrative blast.

The pineal gland of adult rats was examined immunohistochemically and electron microscopically following exposure of the animals to a single blast equivalent to 110 kg TNT explosive. The most dramatic feature in rats killed at 7, 14 and 21 days after the blast was the upsurge of a large number of macrophages/microglia intensely immunostained with OX-42, OX-18, OX-6 and ED1 antibodies. These antibodies recognise the complement type three (CR3) receptors, major histocompatibility complex class I and class II (MHC I and MHC II) antigens and monocyte/macrophage antigens. Cell counts in OX-42 immunostained sections showed a two-fold increase at these intervals but returned to normal values at 28 days. The immunolabelled cells appeared extremely hypertrophic after the blast when compared with those in normal rats. In the latter and in rats killed at 28 days after the blast, immunoreactive cells were sparsely distributed. Ultrastructural study confirmed a wider occurrence of perivascular macrophages/microglia after the blast and the cells were laden with massive amounts of phagosomes resembling degenerating pinealocyte processes. It is concluded that the seemingly quiescent macrophages/microglia present normally in pineal gland were activated by the external blast force. The induced changes including the increase in cell numbers and endocytosis, however, were reversible in longer surviving animals.

Animals↗

The human pineal gland in malignancy.

The weight and degree of calcification of 500 pineal glands has been measured. The degree of cellularity, the size of the pineocyte nuclei and the extent of degeneration has been estimated in histological examinations of the glands. There are some differences in the weight of the gland in males and females of different ages and part of this is due to variations in the amount of calcium in the glands. There is only a minor decrease in the cellularity of the glands with increasing age, and this is accompanied in females by a slight increase in fibrosis and gliosis. The weight of the gland is high in patients dying from trauma and burns. No statistical differences are found in the weight of the pineal glands from patients dying of malignant and non-malignant conditions, although in most age-groups the glands tend to be smaller in patients dying of malignancy. On the other hand patients dying from carcinoma of the breast and from melanoma have much larger glands than those dying from sarcoma.

Acute Disease↗

Arylamine and arylalkylamine N-acetyltransferases in retina, pineal gland, brain and liver of chicks: a comparative study.

Regulation of arylamine N-acetyltransferase (A-NAT) and arylalkylamine N-acetyltransferase (AA-NAT) was examined in retina, pineal gland, brain and liver of chicks. Enzyme activities were determined using as substrates p-phenetidine and procainamide for A-NAT, tryptamine and phenethylamine for AA-NAT. The activity of A-NAT in all tissues studied does not appear to be regulated by a light-dark cycle. On the other hand, AA-NAT showed distinct light-dark dependent changes (with high values at night) in the retina and pineal gland, but not in brain and liver. The nocturnal increase of retinal and pineal AA-NAT activity was prevented by cycloheximide; the drug did not affect A-NAT activity in these tissues. Treatment of light-adapted chicks with aminophylline significantly increased AA-NAT activity of the retina and pineal gland, without altering the enzyme activity in brain and liver. In these animals, the activity of A-NAT (procainamide) did not change in any tissue studied, whereas the enzyme activity measured using p-phenetidine as a substrate did decrease but only in the retina. A similar pattern of changes in retinal A-NAT and AA-NAT activities was observed after intraocular injection of d,b-cAMP. The rate of inactivation at 4 degrees C was significantly slower for AA-NAT than A-NAT. NATs from brain and liver displayed the highest and lowest, respectively, liability in the cold. The results indicate that the chick retina contains both A-NAT and AA-NAT. The two enzymes have distinct characteristics and the regulation of their activities is different. The retinal A-NAT is similar to A-NAT present in other tested tissues; however, AA-NAT can be induced at night only in the retina and pineal gland. It is suggested that there are two forms of retinal A-NAT, and that, under specified conditions, the activity of one form (A-NAT; p-phenetidine) may be regulated in an opposite manner to AA-NAT activity.

Analysis of Variance↗

Nyctohemeral rhythm in the levels of S-adenosylmethionine in the rat pineal gland and its relationship to melatonin biosynthesis.

Liquid chromatographic techniques that permit the simultaneous analysis of S-adenosylmethionine, melatonin, and its intermediary metabolites N-acetyl-5-hydroxytryptamine and 5-hydroxytryptamine within individual pineal glands have been developed. S-Adenosylmethionine has been shown to undergo a marked nyctohemeral rhythm in the pineal gland of the rat, with maximal levels occurring during the light period and minimal levels during the dark period. Detailed studies of the temporal relationships between the levels of S-adenosylmethionine and those of melatonin and its intermediary metabolites suggest that an association exists between the levels of S-adenosylmethionine and the status of the biosynthesis of melatonin. Exposure of animals to continuous light and the administration of the beta-adrenoreceptor antagonist propranolol were both found to inhibit the induction of melatonin synthesis and prevent the reduction in the levels of S-adenosylmethionine during the dark period. As a corollary the induction of melatonin biosynthesis following the administration of the beta-adrenoreceptor agonist isoproterenol during the light period was accompanied by a marked decrease in the levels of S-adenosylmethionine in the pineal gland. The significance of the link between the nyctohemeral rhythms in the levels of S-adenosylmethionine and the biosynthesis of melatonin in the pineal gland is discussed in the context of the therapeutic efficacy of S-adenosylmethionine as an antidepressant.

Animals↗

Adrenergic regulation and diurnal rhythm of p38 mitogen-activated protein kinase phosphorylation in the rat pineal gland.

In this study, we investigated adrenergic and photoneural regulation of p38MAPK phosphorylation in the rat pineal gland. Norepinephrine (NE), the endogenous neurotransmitter, dose-dependently increased the levels of phosphorylated MAPK kinase 3/6 (MKK3/6) and p38MAPK in rat pinealocytes. Time-course studies showed a gradual increase in MKK3/6 and p38MAPK phosphorylation that peaked between 1 and 2 h and persisted for 4 h post NE stimulation. In cells treated with NE for 2 and 4 h, the inclusion of prazosin or propranolol reduced NE-induced MKK3/6 and p38MAPK phosphorylation, indicating involvement of both alpha- and beta-adrenergic receptors for the sustained response. Whereas treatment with dibutyryl cAMP or ionomycin mimicked the NE-induced MKK3/6 and p38MAPK phosphorylation, neither dibutyryl cGMP nor 4beta-phorbol 12-myristate 13-acetate had an effect. The NE-induced increase in MKK3/6 and p38MAPK phosphorylation was blocked by KT5720 (a protein kinase A inhibitor) and KN93 (a Ca(2+)/calmodulin-dependent kinase inhibitor), but not by KT5823 (a protein kinase G inhibitor) or calphostin C (a protein kinase C inhibitor). In animals housed under a lighting regimen with 12 h of light, MKK3/6 and p38MAPK phosphorylation increased in the rat pineal gland at zeitgeber time 18. The nocturnal increase in p38MAPK phosphorylation was blocked by exposing the animal to constant light and reduced by treatment with propranolol, a beta-adrenergic blocker. Together, our results indicate that activation of p38MAPK is under photoneural control in the rat pineal gland and that protein kinase A and intracellular Ca(2+) signaling pathways are involved in NE regulation of p38MAPK.

Adrenergic Antagonists↗