Induction of photosensitivity in neonatal rat pineal gland.
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Pineal glands removed from neonatal rats at 5, 7, and 9 days of age and explanted into short-term culture, synthesized melatonin when stimulated with norepinephrine (NE); their melatonin synthesis could not be suppressed with bright white light. Dispersed pineal cell cultures or pineal explants prepared from 1-day-old neonates and held in culture for 7 or 9 days also synthesized melatonin when stimulated with NE, but in these cases melatonin synthesis was significantly suppressed by light, demonstrating that the pineals had become photosensitive while in culture. The development of photosensitivity in culture could be partially or completely abolished by the continuous presence of 1 or 10 microm of NE in the culture medium. The pineals of all nonmammalian vertebrates are photoreceptive, whereas those of mammals do not normally respond to light. We hypothesize that a mechanism to suppress pineal photosensitivity by using NE released from sympathetic nerve endings evolved early in the history of mammals. (+info)
Negative regulation of cytosolic phospholipase A(2) by melatonin in the rat pineal gland.
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In this paper evidence that supports a new role for melatonin as a negative endogenous regulator of cytosolic phospholipase A(2) (cPLA(2)) is presented. When rat pineal glands were incubated in culture, time-dependent release of arachidonic acid (AA) was observed, which was significantly inhibited by a known 85-kDa cPLA(2) inhibitor, methyl arachidonyl fluorophosphonate. Co-incubation with melatonin inhibited the AA release in a concentration-dependent manner, and this decrease was accompanied by a reduction of cPLA(2) protein and mRNA expression. Melatonin-receptor agonists, 2-iodo-N-butanoyl-5-methoxytryptamine and 5-methoxycarbonylamino-N-acetyltryptamine, also decreased AA release and cPLA(2) protein and mRNA levels, while pre-incubation with the melatonin receptor antagonists luzindole and 2-phenylmelatonin abolished the melatonin effect. In vivo, as melatonin production reflected a typical diurnal variation, endogenous non-esterified AA and cPLA(2) mRNA levels in the rat pineal gland showed an off-phase diurnal pattern in relation to melatonin levels. Intravenous administration of isoproterenol, which has been shown to elevate melatonin production, also decreased the levels of non-esterified AA and cPLA(2) mRNA significantly. Direct administration of melatonin to rats by intravenous injection decreased the levels of non-esterified AA, cPLA(2) protein and mRNA in rat pineal glands. In conclusion, melatonin endogenously down-regulates cPLA(2) expression, presumably through melatonin-receptor-mediated processes. (+info)
Asymmetric nodal signaling in the zebrafish diencephalon positions the pineal organ.
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The vertebrate brain develops from a bilaterally symmetric neural tube but later displays profound anatomical and functional asymmetries. Despite considerable progress in deciphering mechanisms of visceral organ laterality, the genetic pathways regulating brain asymmetries are unknown. In zebrafish, genes implicated in laterality of the viscera (cyclops/nodal, antivin/lefty and pitx2) are coexpressed on the left side of the embryonic dorsal diencephalon, within a region corresponding to the presumptive epiphysis or pineal organ. Asymmetric gene expression in the brain requires an intact midline and Nodal-related factors. RNA-mediated rescue of mutants defective in Nodal signaling corrects tissue patterning at gastrulation, but fails to restore left-sided gene expression in the diencephalon. Such embryos develop into viable adults with seemingly normal brain morphology. However, the pineal organ, which typically emanates at a left-to-medial site from the dorsal diencephalic roof, becomes displaced in position. Thus, a conserved signaling pathway regulating visceral laterality also underlies an anatomical asymmetry of the zebrafish forebrain. (+info)
Light induces chromatin modification in cells of the mammalian circadian clock.
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The mammalian circadian clock resides in neurons of the hypothalamic suprachiasmatic nucleus (SCN). Light entrains phase resetting of the clock using the retino-hypothalamic tract, via release of glutamate. Nighttime light exposure causes rapid, transient induction of clock and immediate-early genes implicated in phase-shifting the pacemaker. Here we show that a nighttime light pulse caused phosphorylation of Ser10 in histone H3's tail, in SCN clock cells. The effect of light was specific, and the kinetics of H3 phosphorylation were characteristic of the early response, paralleling c-fos and Per1 induction. Using fos-lacZ transgenic mice, we found that H3 phosphorylation and Fos induction occurRed in the same SCN neurons. Systemic treatment with the GABAB receptor agonist baclofen prevented light-induced c-fos and Per1 expression and H3 phosphorylation, indicating that one signaling pathway governs both events. Our results suggest that dynamic chromatin remodeling in the SCN occurs in response to a physiological stimulus in vivo. (+info)
Lysosomal enzyme activities are decreased in the retina and their circadian rhythms are different from those in the pineal gland of rats fed an alpha-linolenic acid-restricted diet.
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The retinal rod outer segment (ROS) is shed and digested daily by phagosomes in retinal pigment epithelial (RPE) cells. We previously observed significantly fewer large phagosomes in rats fed an alpha-linolenic acid (ALNA)-deficient diet. Rats fed a safflower oil diet (ALNA-restricted) or a perilla oil diet (ALNA-sufficient) through two generations were adapted to a 24-h cycle with light from 0700 to 1900 h. They were killed at 0500, 0900, 1300 and 1700 h to determine the activities of four lysosomal enzymes in retina, including beta-glucosidase, beta-glucuronidase, hexosaminidase and acid phosphatase. The enzyme activities at 0500 h were the lowest and then increased gradually until 1700 h, exhibiting similar circadian rhythms in the two dietary groups. However, the activities at each time point were significantly lower in the safflower group. In the pineal gland, the activities were maximum at 1300 h, except for beta-glucosidase, and were not different between groups. These diets had qualitatively similar but quantitatively different effects on the fatty acid compositions of the retina and the pineal gland. These results indicate that decreased amplitudes in electroretinogram and altered size distribution of phagosomes, as induced by a restricted intake of ALNA, are associated with decreased lysosomal enzyme activities in the retina but not in the pineal gland. (+info)
Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease.
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Vogt-Koyanagi-Harada (VKH) disease (and sympathetic ophthalmia) is an ocular inflammatory disease that is considered to be a cell-mediated autoimmune disease against melanocytes. The purpose of this study was to determine the Ags specific to VKH disease and to develop an animal model of VKH disease. We found that exposure of lymphocytes from patients with VKH disease to peptides (30-mer) derived from the tyrosinase family proteins led to significant proliferation of the lymphocytes. Immunization of these peptides into pigmented rats induced ocular and extraocular changes that highly resembled human VKH disease, and we suggest that an experimental VKH disease was induced in these rats. We conclude that VKH disease is an autoimmune disease against the tyrosinase family proteins. (+info)
Effect of brefeldin A on melatonin secretion of chick pineal cells.
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Melatonin is secreted from the pineal gland in a circadian manner. It is well established that the synthesis of melatonin shows a diurnal rhythm reflecting a daily change in serotonin N-acetyltransferase (NAT) activity, and the overall secretion of melatonin requires a cellular release process, which is poorly understood. To investigate the possible involvement of Golgi-derived vesicles in the release, we examined the effect of brefeldin A (BFA), a reversible inhibitor of Golgi-mediated secretion, on melatonin secretion of cultured chick pineal cells. We show here that treatment with BFA completely disassembles the Golgi apparatus and reduces melatonin secretion. In more detailed time course experiments, however, the inhibition of melatonin secretion is only observed after the removal of BFA in parallel with the reassembly of the Golgi apparatus. This inhibition of melatonin secretion is not accompanied by accumulation of melatonin in the cells. These observations indicate that chick pineal melatonin is released independently of the Golgi-derived vesicles, and suggest inhibition of melatonin synthesis after the removal of BFA. By measuring the activities and mRNA levels of melatonin-synthesizing enzymes, we found that the removal of BFA specifically inhibits NAT activity at the protein level. On the other hand, BFA causes no detectable phase-shift of the chick pineal oscillator regulating the circadian rhythm of melatonin secretion. The results presented here suggest that the Golgi-mediated vesicular transport is involved in neither the melatonin release nor the time-keeping mechanism of the circadian oscillator, but rather contributes to the regulation of NAT activity. (+info)
A nodal signaling pathway regulates the laterality of neuroanatomical asymmetries in the zebrafish forebrain.
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Animals show behavioral asymmetries that are mediated by differences between the left and right sides of the brain. We report that the laterality of asymmetric development of the diencephalic habenular nuclei and the photoreceptive pineal complex is regulated by the Nodal signaling pathway and by midline tissue. Analysis of zebrafish embryos with compromised Nodal signaling reveals an early role for this pathway in the repression of asymmetrically expressed genes in the diencephalon. Later signaling mediated by the EGF-CFC protein One-eyed pinhead and the forkhead transcription factor Schmalspur is required to overcome this repression. When expression of Nodal pathway genes is either absent or symmetrical, neuroanatomical asymmetries are still established but are randomized. This indicates that Nodal signaling is not required for asymmetric development per se but is essential to determine the laterality of the asymmetry. (+info)