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Structure of the ovine pineal gland during prenatal development.

The structure of the pineal gland of 32 clinically healthy ovine embryos at different stages of development was studied. Embryos were arranged in four age groups, each containing eight embryos (four males and four females), defined in terms of the most relevant histological features: group 1 (27 to 69 days of prenatal development), group 2 (70 to 97 days), group 3 (98 to 116 days), and group 4 (117 to 150 days). At around 30 days of prenatal life, according to topographic criteria, the pineal outline begins to differentiate into a dorsal evagination of the diencephalic medium line, close to the anterior and posterior commissures. The growth of the pineal is biphasic. The ontogenic-proliferative phase begins at 30 days and includes the invasion of ependymal cells and the proliferation of the pineal parenchyma cells. The hypertrophic-differentiation phase includes the volume increment of the pinealoblasts and their differentiation into pinealocytes; this occurs at around 118 days. At around 98 days, the gland acquires its definitive compact appearance due to 1) glandular growth in constant volume and 2) the obliteration of pineal recess. The glandular structure displays a parenchyma made up of pinealoblasts, interstitial cells, and cells containing pigment. The pineal stroma is structured in pseudolobes formed by reticular and collagen fiber septae, which constitute together the interstitial cell prolongation net, which is the support structure of the whole glandular cytology. Capillaries are detected all over the glandular surface, being more abundant in the medullary zone. At around 98 days of prenatal development, VIP (Vasoactive Intestinal Peptide) positive fibers, distributed around blood vessels and among pinealoblasts were detected.

Animals↗

Muscarinic effects on the hydroxy- and methoxyindole pathway in the rat pineal gland.

[3H]Quinuclidinyl benzylate ([3H]QNB)-binding sites, showing similar properties to cholinergic muscarinic receptors in other tissues, were disclosed in the rat pineal gland. Functionality of these receptors was demonstrated, as in-vitro muscarinic activation by pilocarpine increased the pineal metabolic production of the hydroxyindole derivatives 5-hydroxytryptophan and serotonin, with a slight effect on melatonin biosynthesis. Electric-field stimulation of pineal slices caused similar metabolic effects. These effects were inhibited by muscarinic blockade with atropine and enhanced by neostigmine inactivation of acetylcholinesterase. These results suggest that acetylcholine is the neurotransmitter involved. Cholinergic activity may, therefore, regulate indole metabolism in the pineal gland.

Animals↗

Alpha rhythm and the pineal gland.

Alpha rhythm is classically described as a bilateral posterior rhythm of substantially constant frequency in the range of 8-13 Hz which is enhanced by mental relaxation and blocked by attention. Since the full expression of alpha rhythm has been shown to occur coincident with puberty, it is possible that the establishment of alpha rhythm is subject to neuroendocrine influences which govern psychosexual maturation. There is ample evidence to indicate that the pineal gland is implicated in cerebral maturation and psychosexual development. Nocturnal plasma melatonin levels have been shown to decline progressively throughout childhood reaching a nadir at puberty. Since administration of melatonin has been reported to block alpha rhythm, it is proposed that the progressive decline in melatonin secretion during childhood facilitates the maturation of the alpha rhythm. Consequently, the presence of alpha rhythm could be used as a neurophysiological marker for the activity of the pineal gland and disorders associated with absent or delayed maturation of the alpha rhythm such as autism, dyslexia, personality disorders, epilepsy, Tourette's syndrome, and schizophrenia might be related to disturbances of pineal melatonin functions in early life. Moreover, since the EEG patterns associated with cerebral immaturity (i.e., slowing, absence of alpha activity) are more pronounced in the left hemisphere, this hypothesis implies differential influence of the pineal gland on hemispheric maturation potentially accounting for the vulnerability of the left hemisphere to cerebral insults.

Alpha Rhythm↗

Ultrastructural study of the developing blood capillaries in the pineal gland of the domestic fowl.

The ultrastructure of the pineal gland capillaries in chick embryos of 7, 14 and 19 days of incubation and in three month chicks has been analyzed. The results show that vascular primordia are detectable among the pineal developing vesicles on the 7th incubation day. Significant maturative changes in the capillary wall (flattening of the endothelial cells, appearance of pores, narrowing of the perivascular spaces and formation of the endothelial basement lamina) take place during the last days of the embryonic life and are concluded only after the hatching. Relationships between the vasculogenetic and the morpho-histogenetic processes in the pineal body, and some differences in the maturative changes of the vascular wall of the pineal and other chick embryo endocrine glands, have been briefly discussed.

Animals↗

Rhodopsin kinase activity in the mammalian pineal gland and other tissues.

Rhodopsin kinase, an enzyme involved in photochemical transduction in the retina, has been found in the mammalian pineal gland in amounts equal to those in the retina; other tissues had 7 percent of this amount, or less. This finding suggests that, in mammals, rhodopsin kinase functions in the pineal gland and other tissues to phosphorylate rhodopsin-like integral membrane receptors and is thereby involved in signal transduction.

Animals↗

Rapid recovery of function after partial denervation of the rat pineal gland suggests a novel mechanism for neural plasticity.

The activity of serotonin N-acetyltransferase (NATase) in the rat pineal gland exhibits a large (approximately 100-fold) circadian variation, with peak activity occurring in the dark part of the light/dark cycle. Surgical removal of both superior cervical ganglia abolishes this rhythm in enzyme activity. Unilateral ganglionectomy caused a 75% decrease in NATase activity during the dark period immediately following the operation; however, by the subsequent dark period (32 hr after operation) the rhythm in NATase activity had returned to normal. Similar results were found after the internal carotid nerve was cut, and data are presented indicating that this is the postganglionic trunk by which sympathetic neurons reach the pineal gland. Denervation of one superior cervical ganglion (unilateral "decentralization") also produced a 75% decrease in NATase activity during the dark period immediately following the operation; however, after decentralization, enzyme activity did not return to normal in subsequent cycles. It is hypothesized that this recovery is due to loss of norepinephrine uptake sites in the degenerating sympathetic nerve terminals. As a result of decreased norepinephrine uptake, the effectiveness of the norepinephrine released by surviving neurons may be enhanced. This hypothesis is supported by experiments in which pharmacological blockade of norepinephrine uptake in unilaterally decentralized animals increased NATase activity to control levels. We propose that neural systems which use transmitter uptake as the mechanism of transmitter inactivation have a built-in "reserve stimulatory capacity."

Acetyltransferases↗

Darkness-induced changes in noradrenergic input determine the 24 hour variation in beta-adrenergic receptor density in the rat pineal gland: in vivo physiological and pharmacological evidence.

In male rats housed under a 14:10 LD cycle (lights on at 0600 h), pineal beta-adrenergic receptors, assessed as 125Iodopindolol (IPIN) binding to membrane preparations, showed a 24 hour variation characterized by a nocturnal increase that peaked around middark (2300 h-0200 h) and a decrease during the latter half of the dark period. Animals exposed to light for 3 hours into the normal dark period showed a similar increase in IPIN binding that was prevented by a single sc injection (0.5 mg/kg) of isoproterenol (ISO). The decrease in IPIN binding observed after middark was prevented both by moving the animals to light at 0200 h and by propranolol administration (20 mg/kg). Likewise, the reduction in IPIN binding was induced in light exposed animals both by ISO administration (in a dose dependent manner) and by injection of norepinephrine (NE) plus the catecholamine uptake blocker desmethylimipramine (DMI). DMI alone was without effect. Chronic denervation of the pineal gland by superior cervical ganglionectomy (SCGx) increased IPIN binding to levels not higher than those observed at middark. The results suggest that rat pineal beta-adrenergic receptors are regulated in a rhythmic 24 hour pattern. A decrease in density (downregulation) induced by a darkness-associated increase in NE release, occurs late in the night before lights on; recovery from the down regulated state (upregulation) occurs during the light and early dark phase, reaching a maximum density of beta-adrenergic receptors at middark not different from that observed in chronically denervated pineal glands.

Animals↗

Developmental pattern of cell type-specific calretinin immunoreactivity in the postnatal gerbil pineal gland

The postnatal development of immunoreactivity for the neuronal calcium-binding protein calretinin in the pineal gland of the Mongolian gerbil was investigated using immunostaining of serial semithin sections. Calretinin-positive pineal cells could readily be visualized from the day of birth (P0) onwards and coexpressed the intermediate filament (IF) protein vimentin. During the first half of the first postnatal week, many of the calretinin-/vimentin-positive cells were also immunopositive for synaptophysin and neuron-specific enolase (NSE) and thus corresponded to pinealocytes. However, the expression of calretinin in pinealocytes was only transitory and declined towards the end of the first postnatal week. Thereafter, calretinin immunoreactivity became restricted to vimentin-positive interstitial glial cells. Therefore, in the gerbil pineal gland, calretinin obviously is not required in mature pinealocytes but instead serves as yet unknown functions in interstitial cells. The unusual calretinin expression pattern adds to the notion that pineal interstitial cells differ from glial cells of other brain regions. This conclusion is also underlined by our present detection of the neuronal marker protein PGP 9.5 in interstitial cells during postnatal development.

Journal Article↗

Histophysiological evidence for the secretion of polypeptides by the pineal gland.

Histophysiological examinations of the bovine and monkey pineal gland indicate that this organ may be involved in the secretion of polypeptides. Using various histochemical procedures designed to identify peptide-secreting cells, granules and/or droplets of presumptive secretory product were identified within cellular processes, within the walls of blood vessels and associated with multilayered corpuscles (corpora arenacea). In bovine pineal tissue, the stained material was found most often in what appeared to be pinealocyte processes, as perivascular granules and associated with multilayered corpuscles. In the monkey pineal the stainable material was more distinct; this was probably due to the earlier fixation of the glands after death of the animals. In this species, the presumptive secretory material was found in nerve fibers, occasionally in glial cell and pinealocyte processes and within and around the walls of capillaries. In nerve fibers, the stained material sometimes resembled Herring bodies of the posterior pituitary gland. Similar material appeared to be located in capillary endothelial cells and within multilayered corpuscles. In pineal tissue of both species, calcium was detectable histochemically within multilayered corpuscles. Although tinctorially different, the presumptive neurosecretory material was similar to that found in the posterior pituitary gland. As a working hypothesis, we propose that polypeptides may be released from cells in conjunction with a carrier protein and that the mechanism of secretion of the polypeptide into the vascular system may involve its exchange for calcium. The calcium is then theoretically deposited in the multilayered corpuscles.

Animals↗

Neurotransmitter regulation of arginine vasotocin release from rat pineal glands in vitro.

Studies were performed to determine the effects of neurotransmitters on arginine vasotocin (AVT) release in vitro. Rat pineal glands were incubated with 10(-8)M or 10(-6)M norepinephrine (NE), dopamine (DA), serotonin (5HT), and acetylcholine (ACH) for eight h after which the concentrations of AVT in the media were determined by radioimmunoassay. With the exception of ACH, none of the neurotransmitters had a significant effect on AVT release. ACH significantly (P less than 0.05) elevated AVT release in vitro at the 10(-6)M concentration but not at the 10(-8)M concentration. The data indicate that ACH may play a role in the regulation of rat pineal gland secretion of AVT in vitro.

Acetylcholine↗

Structure of the pineal gland in the adult cat.

The ultrastructure of the pineal gland in the adult cat is described and compared with that of other mammals. Connective tissue spaces showed capillaries with nonfenestrated endothelia and numerous unmyelinated nerve fibers. In the proximal region of the gland, myelinated nerve fibers coming from the anterior commissure were also found. Cat pinealocytes showed a nucleus with prominent nucleoli, a well developed Golgi apparatus, centrioles, granular endoplasmic reticulum, ribosomes, abundant microtubuli and enlarged mitochondria. Pinealocytes showed several long processes with bulbous endings filled with clear vesicles and scarce "synaptic" ribbons. Pineal astrocytes and their processes were characterized by the presence of abundant filaments.

Animals↗

Presence of two neurophysins in the human pineal gland.

The tentative identification of two neurophysins in human pineal glands is reported. The presence of these carrier-proteins for neurohormones was demonstrated by two different radioimmunossays: one highly specific for human pituitary estrogen-stimulated neurophysin (h-ESN) and the second for pituitary bovine neurophysin II (b-NII). These neurophysins accounted for about 0.425% of the total soluble pineal proteins. They were eluted from Sephadex G-75 column with the same elution volume as 125I labeled h-ESN. Their dilution curves were parallel to the standard curves of h-ESN and b-NII, respectively. Electrophoresis on polyacrylamide gel separated two distinct neurophysins. The less anodic neurophysin corresponding to b-NII and the faster moving one to h-ESN. The two proteins were named human pineal neurophysins I and II (h-PNI and h-PNII) in the order of their electrophoretic mobility. Purification of pineal neurophysins by isoelectric focusing resulted also in the separation of two neurophysins: one, recognized by antibody against h-ESN with an isoelectric point (pI) of 4.6, the other recognized by antibody against b-NII with a pI of 4.9. The presence of neurohormone(s), assessed by radioimmunoassay for [8-arginine] vasopressin, was also demonstrated. Under optimal conditions for the association the neurophysin and the neurohormone were eluted from Sephadex columns as a complex. This complex could be dissociated in 0.1N formic acid and the neurophysin and the neurohormone separated on Sephadex G-75.

Chromatography, Gel↗

Temporal-spatial characterization of chicken clock genes: circadian expression in retina, pineal gland, and peripheral tissues.

The molecular core of the vertebrate circadian clock is a set of clock genes, whose products interact to control circadian changes in physiology. These clock genes are expressed in all tissues known to possess an endogenous self-sustaining clock, and many are also found in peripheral tissues. In the present study, the expression patterns of two clock genes, cBmal1 and cMOP4, were examined in the chicken, a useful model for analysis of the avian circadian system. In two tissues which contain endogenous clocks--the pineal gland and retina--circadian fluctuations of both cBmal1 and cMOP4 mRNAs were observed to be synchronous; highest levels occurred at Zeitgeber time 12. Expression of these genes is also rhythmic in several peripheral tissues; however, the phases of these rhythms differ from those in the pineal gland and retina: in the liver the peaks of cMOP4 and cBmal1 mRNAs are delayed 4-8 h and in the heart they are advanced by 4 h, relative to those in the pineal gland and retina. These results provide the first temporal characterization of cBmal1 and cMOP4 mRNAs in avian tissues: their presence in avian peripheral tissues indicates they may influence temporal features of daily rhythms in biochemical, physiological, and behavioral functions at these sites.

ARNTL Transcription Factors↗

Down-regulation of the nocturnally elevated guanylyl cyclase activity in the rat pineal gland.

Previous studies have shown that in the rat pineal, the cytosolic and the particulate forms of guanylyl cyclase (GC) activity undergo a biphasic 24-h rhythm with two prominent peaks, one in the middle of the light phase and the other in the middle of the dark phase. In this study we investigated whether the well established photo-neural adrenergic regulatory processes identified for pineal melatonin synthesis also apply to the nocturnal elevation of GC activity. A 10-min light pulse given in the middle of the dark phase decreases the cytosolic and the particulate forms of GC. Administration of the beta-receptor blocker propranolol did not depress the nocturnally elevated GC activity. Sympathetic denervation of the pineal gland by means of superior cervical ganglionectomy did not noticeably affect nocturnal GC activity studied 6 days and 2 months after surgery. In vitro, administration of the nitric oxide synthase blocker NG-mono-methyl-L-arginine (NMMA) for 10 min did not change the cytosolic form of GC activity. The results obtained reveal that in the rat pineal, the down-regulation of the nocturnally elevated GC activity does not appear to be adrenergically mediated.

Animals↗

Benign symptomatic glial cysts of the pineal gland: a report of seven cases and review of the literature.

Seven cases of clinically symptomatic benign glial cyst of the pineal gland are reported. The cysts' size ranged from 1.0-4.5 cm in diameter. They were characterised by a golden or, less frequently, brown-reddish proteinaceous or haemorrhagic fluid content. The cyst wall, up to 2 mm thick, consisted of clusters of normal pineal parenchymal cells, often compressed and distorted, surrounded by reactive gliotic tissue which sometimes contained Rosenthal fibres. The presenting clinical features included headache (6/7), signs of raised intracranial pressure, partial or complete Parinaud's syndrome (5/7), cerebellar deficits (2/7), corticospinal and corticopontine fibre (2/7) or sensory (1/7) deficits, and emotional disturbances (2/7). CT and MRI (in 2/7 cases) scans showed a hypodense or nonhomogeneous lesion in the region of the pineal gland, with or without contrast enhancement. Surgical excision resulted in complete clearance of the symptoms in 5/7 patients. The previous literature is reviewed and the clinicopathological correlations and the possible pathogenetic mechanisms are discussed. The need to distinguish this benign lesion from other mass lesions of the pineal region, in particular from pinealocytoma, is stressed.

Adult↗

Pineal gland of a nocturnal bird, Indian spotted owlet, Athene brama: morphological and endocrine observations.

It has been reported that owls (Strigiformes) do not have a pineal gland. However, our light microscopy study revealed an intermediate form of tubulofollicular and solid-type large pineal gland in a tropical owlet, Athene brama. The epithelial cells forming follicles (6-8) in the distal region and the solid cluster of parenchymal cells of different diameters in the proximal region anteriorly tapered with a long cylindrical stalk and continued into commissural organs and choroid plexus. The intrapineal localization of perivascular nerve fibers and blood vessels clearly explained the sympathetic innervation as well as vascularization of this neuroendocrine gland. Further, electron microscopy revealed a developed intracellular structure of the pinealocytes with a large number of mitochondria, Golgi bodies, and granular as well as clear vesicles in the process terminals. The evidence of intrapinealocyte lipid droplets and dense bodies and a moderate amount of melatonin in plasma (ranging from 100-365 pg/mL) during different reproductive phases finally proved a defined secretory activity of the gland in this tropical, nocturnal bird.

Animals↗

"Synaptic" ribbons and spherules of the rat pineal gland: day/night changes in vitro?

In the present study pineal glands of rats aged 69-71 days were studied in vivo and in vitro with respect to day/night changes of "synaptic" ribbons and spherules. It was found that ribbons outnumber spherules by a factor of 3. In vivo, both ribbons and spherules show a roughly 3-fold increase in number at 1 a.m. when compared to 1 p.m. Up to 39 h in vitro, the two structures in question did not reveal day/night differences in amount, suggesting that diurnal rhythmicity of the gland did apparently not persist in organ culture. After 3 h in organ culture, the spherules, but not the ribbons, showed a striking increase in number, showing that ribbons and spherules may be governed by different mechanisms.

Animals↗