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  • 1
    Electronic Resource
    Electronic Resource
    The Decrease of Pineal Melatonin Production with Age (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 719 (1994), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1994.tb56819.x
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  • 2
    Electronic Resource
    Electronic Resource
    Evidence for melatonin synthesis in rodent Harderian gland: A dynamic in vitro study (1998)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 25 (1998), S. 0 
    Details
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: : Melatonin content and release from Harderian glands (HGs) has been measured by an in vitro perifusion technique in three rodent species: Wistar rat, Syrian hamster, and Siberian hamster. Melatonin immunoreactive concentrations in HGs of animals killed at 10.00 hr were 0.31 ± 0.031 pg/mg gland in male Wistar rat, 0.54 ± 0.026 pg/mg gland in male Siberian hamster, 0.17 ± 0.070 and 0.20 ± 0.059 pg/mg gland in male and female Syrian hamster, respectively. In all species examined, isolated HGs perifused for 9–15 hr released melatonin but did not stabilize their melatonin release rate. No sex-related difference could be noted in the HG melatonin release rate. The total amount of melatonin released over a 15 hr long perifusion was about 0.075 ± 0.004 ng/15 h/mg gland and 0.063 ± 0.010 ng/15 hr/mg gland in male and female Wistar rat, respectively; 0.155 ± 0.019 ng/15 hr/mg gland and 0.141 ± 0.006 ng/15 hr/mg gland in male and female Siberian hamster, respectively; 0.035 ± 0.003 ng/15 hr/mg gland and 0.045 ± 0.004 ng/15 hr/mg gland in male and female Syrian hamster, respectively. This amount, which is higher than the tissue levels, demonstrates the de novo melatonin synthesis. This is confirmed by the fact that infusion of the indoleamine precursor, tryptophan (TRP), stimulated melatonin secretion from HGs. The melatonin release is increased by 2.5-fold in male and female Wistar rat, 1.5-fold in male and female Siberian hamster, and 2.0- and 3.0-fold in male and female Syrian hamster, respectively. Treatment with a TRP hydroxylase inhibitor, para-chlorophenylalanine, reduced basal melatonin release and inhibited the TRP-induced melatonin stimulation. Kinetics and amounts of melatonin released were not affected by pinealectomy, ruling out a possible plasmatic origin of the HG melatonin. Isoproterenol, a β-adrenergic agonist, and dibutyryl cyclic AMP, a cyclic AMP analogue, failed to stimulate HG melatonin secretion. In conclusion, these results confirm the presence of melatonin in the HGs and demonstrate that melatonin is synthesized in and released from isolated rodent HGs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-079X.1998.tb00386.x
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  • 3
    Electronic Resource
    Electronic Resource
    Presynaptic and Postsynaptic Effects of Neuropeptide Y in the Rat Pineal Gland (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 62 (1994), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Neuropeptide Y is colocalized with noradrena-line in sympathetic fibers innervating the rat pineal gland. In this article we present a study of the effects and mechanisms of action of neuropeptide Y on the pineal noradrenergic transmission, the main input leading to the rhythmic secretion of melatonin. At the presynaptic level, neuropeptide Y inhibits by 45%, with an EC50 of 50 nM, the potassium-evoked noradrenaline release from pineal nerve endings. This neuropeptide Y inhibition occurs via the activation of pertussis toxin-sensitive G protein-coupled neuropeptide Y-Y2 receptors and is independent from, but additive to, the α2-adrenergic inhibition of noradrenaline release. At the postsynaptic level, neuropeptide Y decreases by a maximum of 35%, with an EC50 of 5 nM, the β-adrenergic induction of cyclic AMP elevation via the activation of neuropeptide Y-Y1 receptors. This moderate neuropeptide Y-induced inhibition of cyclic AMP accumulation, however, has no effect on the melatonin secretion induced by a β-adrenergic stimulation. On the contrary, in the presence of 1 mM ascorbic acid, neuropeptide Y potentiates (up to threefold) the melatonin secretion. In conclusion, this study has demonstrated that neuropeptide Y modulates the noradrenergic transmission in the rat pineal gland at both presynaptic and postsynaptic levels, using different receptor subtypes and transduction pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1994.62062464.x
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  • 4
    Electronic Resource
    Electronic Resource
    Tryptophan Hydroxylase Synthesis Is Induced by 3′, 5′-Cyclic Adenosine Monophosphate During Circadian Rhythm in the Rat Pineal Gland (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 57 (1991), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: : Tryptophan hydroxylase in the rat pineal gland undergoes diurnal rhythmic activity. Rat pineal glands exhibit increased tryptophan hydroxylase activity when incubated with a cyclic AMP analogue in vitro. Cyclic AMP-dependent protein kinase phosphorylates tryptophan hydroxylase, purified from rat brain, without any modification of its enzyme activity under our experimental conditions. Actinomycin O or cydoheximide decreases the stimulating effect of the cyclic AMP analogue on pineal tryptophan hydroxylase activity. Incubation of pineal glands in the presence of [35S]mcthionine showed a cyclic AMP-induced increase in tryptophan hydroxylase synthesis. These results explain the circadian rhythm of tryptophan hydroxylase activity in the rat pineal gland and suggest that the regulation of tryptophan hydroxylase expression by cyclic AMP occurs probably either at the translational level or via transient expression of a transcriptional regulatory element
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1991.tb06346.x
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  • 5
    Electronic Resource
    Electronic Resource
    Pineal arylalkylamine N-acetyltransferase gene expression is highly stimulated at night in the diurnal rodent, Arvicanthis ansorgei (2002)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 15 (2002), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The different mechanisms underlying the control of diurnal vs. nocturnal activity are still unknown. Regarding the nocturnal synthesis of the pineal hormone, melatonin, experiments performed on diurnal sheep or bovine and on nocturnal rat or hamster revealed important differences in the regulation of the melatonin rate-limiting enzyme, arylalkylamine N-acetyltransferase (AA-NAT). These observations raised the hypothesis that melatonin synthesis may be different in nocturnal vs. diurnal animals. In this study, we cloned the cDNA coding for Aa-nat and analysed the mechanisms of AA-NAT enzyme activation in the pineal gland of the diurnal grass rat, Arvicanthis ansorgei, and compared them to those of the nocturnal Wistar rat, Rattus norvegicus. Aa-nat gene sequences of both species are 86.6% identical. In Arvicanthis, Aa-nat gene expression is markedly increased at the beginning of the night and is followed by a large increase in AA-NAT activity and melatonin content. In contrast, at the end of the night, the decrease in AA-NAT activity and melatonin content precedes that of Aa-nat mRNA. A β-adrenergic agonist given at daytime reproduces the nocturnal activation of melatonin synthesis, whereas, a β-adrenergic antagonist given at night-time inhibits AA-NAT activity and melatonin synthesis independently of Aa-nat mRNA. The day–night regulation of melatonin synthesis in the pineal of the diurnal Arvicanthis, involving a transcriptional activation in early night and a post-translational inhibition at late night, is very similar to that of the nocturnal Wistar rat. In conclusion, the fundamental differences underlying melatonin synthesis among species rely upon phylogenetic rather than behavioural differences.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2002.02034.x
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  • 6
    Electronic Resource
    Electronic Resource
    Transcription factor dynamics and neuroendocrine signalling in the mouse pineal gland: a comparative analysis of melatonin-deficient C57BL mice and melatonin-proficient C3H mice (2000)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In rodents, the nocturnal rise and fall of arylalkylamine N-acetyltransferase (AANAT) activity controls the rhythmic synthesis of melatonin, the hormone of the pineal gland. This rhythm involves the transcriptional regulation of the AANAT by two norepinephrine (NE)-inducible transcription factors, e.g. the activator pCREB (phosphorylated Ca2+/cAMP-response element binding protein) and the inhibitor ICER (inducible cAMP early repressor). Most inbred mouse strains do not produce melatonin under standard laboratory light/dark conditions. As melatonin-deficient mice are often the founders for transgenic animals used for chronobiological experimentations, molecular components of neuroendocrine signalling in the pineal gland as an integral part of clock entrainment mechanisms have to be deciphered. We therefore compared calcium signalling, transcriptional events and melatonin synthesis in the melatonin-deficient C57BL mouse and the melatonin-proficient C3H mouse. Pineal glands and primary pinealocytes were cultured and stimulated with NE or were collected at various times of the light/dark (LD) cycle. Changes in intracellular calcium concentrations, the phosphorylation of CREB, and ICER protein levels follow similar dynamics in the pineal glands of both mouse strains. pCREB levels are high during the early night and ICER protein shows elevated levels during the late night. In the C57BL pineal gland, a low but significant increase in melatonin synthesis could be observed upon NE stimulation, and, notably, also when animals were exposed to long nights. We conclude that the commonly used C57BL mouse is not completely melatonin-deficient and that this melatonin-deficiency does not affect molecular details involved in regulating transcriptional events of melatonin synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2000.00990.x
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  • 7
    Electronic Resource
    Electronic Resource
    Glutamatergic clock output stimulates melatonin synthesis at night (2004)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 19 (2004), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The rhythm of melatonin synthesis in the rat pineal gland is under the control of the biological clock, which is located in the suprachiasmatic nucleus of the hypothalamus (SCN). Previous studies demonstrated a daytime inhibitory influence of the SCN on melatonin synthesis, by using γ-aminobutyric acid input to the paraventricular nucleus of the hypothalamus (PVN). Nevertheless, a recent lesion study suggested the presence of a stimulatory clock output in the control of the melatonin rhythm as well. In order to further investigate this output in acute in vivo conditions, we first measured the release of melatonin in the pineal gland before, during and after a temporary shutdown of either SCN or PVN neuronal activity, using multiple microdialysis. For both targets, SCN and PVN, the application of tetrodotoxin by reverse dialysis in the middle of the night decreased melatonin levels. Due to recent evidence of the existence of glutamatergic clock output, we then studied the effect on melatonin release of glutamate antagonist application within the PVN in the middle of the night. Blockade of the glutamatergic input to the PVN significantly decreased melatonin release. These results demonstrate that (i) neuronal activity of both PVN and SCN is necessary to stimulate melatonin synthesis during the dark period and (ii) glutamatergic signalling within the PVN plays an important role in melatonin synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0953-816X.2003.03132.x
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  • 8
    Electronic Resource
    Electronic Resource
    Hypocretin (orexin) in the rat pineal gland: a central transmitter with effects on noradrenaline-induced release of melatonin (2001)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 14 (2001), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Hypocretin-1 (HCRT-1) and hypocretin 2 (HCRT-2), also known as orexin-A and orexin-B, are two neuropeptides derived from the same precursor. Hypocretinergic neurons have been found exclusively in the hypothalamic dorsolateral area. These neurons are implicated in sleep and feeding through activation of specific G-protein-coupled orexin-1 and orexin-2 receptor (OR-R1 and OR-R2). The purpose of this study was to determine the existence of the HCRT peptides in the central input of the rat pineal gland. Further, OR-R1 and OR-R2 expression was determined in the pineal gland and the effect of HCRT-2 on melatonin synthesis and secretion was analysed in dissociated rat pinealocytes. A large contingent of HCRT-positive nerve fibres and terminals were observed in the epithalamus, many of which entered into the pineal parenchyma. A significant number of nerve fibres endowed with positive boutons were identified in the pineal stalk, though the number of positive fibres decreased along the extension of the stalk. So far, no positive fibres have been found in the superficial pineal gland. RT-PCR analysis revealed the expression of OR-R2 mRNA, whereas OR-R1-receptor mRNA was not detected. When tested alone, HCRT-2 had no effect on secretion of melatonin from cultured rat pinealocytes. However, HCRT-2 partially inhibited (by a maximum of 30%) the β-adrenergic-induced melatonin secretion. The same effect was seen on activation of N-acetyltransferase activity. The distribution and the large number of HCRT-positive fibres together with the effect on noradrenaline-mediated melatonin release through specific receptors suggests that these peptides may be significant central transmitters in pineal function, probably mediating homeostatic signals to the pineal gland.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0953-816x.2001.01655.x
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  • 9
    Electronic Resource
    Electronic Resource
    Modulation of photic resetting in rats by lesions of projections to the suprachiasmatic nuclei expressing p75 neurotrophin receptor (2004)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 19 (2004), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The suprachiasmatic nuclei of the hypothalamus (SCN) are the site of the master circadian clock in mammals. The SCN clock is mainly entrained by the light–dark cycle. Light information is conveyed from the retina to the SCN through direct, retinohypothalamic fibres. The SCN also receive other projections, like cholinergic fibres from basal forebrain. To test whether cholinergic afferents are involved in photic resetting, lesions of cholinergic projections were performed in rats with intracerebroventricular (i.c.v.) injections or intra-SCN microinjections of 192 IgG-saporin. When injected in the SCN, this immunotoxin destroys the cholinergic projections and retinohypothalamic afferents that express p75 low-affinity nerve growth factor (p75NGF) receptors. The extent of lesions in the basal forebrain and SCN was assessed by acetylcholinesterase histochemistry, p75NGF receptor, choline acetyl-transferase, calbindin-D28K and VIP immunocytochemistry. The intra-SCN treatment reduced light-induced phase advances by 30%, and induced a complete loss of forebrain and retinal afferents expressing p75NGF receptors within the SCN and a decrease of forebrain cholinergic neurons, most likely those projecting to the SCN. The i.c.v. treatment reduced light-induced phase advances by 40%, increased phase delays and led to extensive damage of forebrain p75NGF-expressing neurons, while sparing half of the fibres expressing p75NGF receptors (retinal afferents?) in the SCN. Because the integrity of forebrain p75NGF-expressing neurons appears to be critical in mediating the effects on light-induced phase advances, we therefore suggest that anterior cholinergic projections expressing p75NGF receptors modulate the sensitivity of the SCN clock to the phase advancing effects of light.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2004.03281.x
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  • 10
    Electronic Resource
    Electronic Resource
    In the rat, exogenous melatonin increases the amplitude of pineal melatonin secretion by a direct action on the circadian clock (2002)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 16 (2002), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effect of exogenous melatonin on pineal melatonin synthesis was studied in the rat in vivo. Daily melatonin profiles were measured by transpineal microdialysis over 4 consecutive days in rats maintained on a 12-h light : 12-h dark schedule (LD 12 : 12). Curve-fitting was used to determine the amplitude of the peak of melatonin production, and the times of its onset (IT50) and offset (DT50). A subcutaneous injection of melatonin (1 mg/kg) at the onset of darkness (ZT12) induced an advance of IT50 on the second day after the treatment, in 50% of the animals kept in LD. When the animals were switched to constant darkness, the treatment caused no detectable advance of IT50, while 70% of individuals showed a significant delay in DT50 2 days after the injection. Locally infusing the drug by reverse microdialysis into the suprachiasmatic nuclei (SCN) failed to enhance the shift in melatonin onset. Following subcutaneous melatonin injection, a significant increase (≈ 100%) in melatonin peak amplitude was observed. This increase persisted over 2 days and occurred only when the melatonin was applied at ZT12, but not at ZT6, 17 or 22. The effect was also observed when the drug was infused directly into the SCN, but not into the pineal. Thus, the SCN are the target site for the effect of exogenous melatonin on the amplitude of the endogenous melatonin rhythm, with a similar window of sensitivity as its phase-shifting effect on the pacemaker.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2002.02176.x
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