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Sample records for pineal neurohormone melatonin

  1. Evidence for feedback control of pineal melatonin secretion.

    PubMed

    Bedrosian, Tracy A; Herring, Kamillya L; Walton, James C; Fonken, Laura K; Weil, Zachary M; Nelson, Randy J

    2013-05-10

    Melatonin is the principle hormonal product of the pineal gland. It is secreted with a robust daily rhythm, peaking near the middle of the night. During the daytime, concentrations remain very low, as exposure to light robustly suppresses its secretion. The regulation of melatonin by light is well-characterized, but an interesting feature of the daily melatonin rhythm is that its peak occurs near the middle of the night and then levels begin to drop hours before morning light exposure. The mechanism underlying the light-independent drop in melatonin during late night remains unspecified. Feedback control is one mechanism of hormone regulation, but no studies thus far have explored the possibility of such regulation in the pineal of white-footed mice (Peromyscus leucopus). The pineal gland and SCN express melatonin receptors, and melatonin regulates its own receptor density in the brain. We investigated the possibility of feedback control of melatonin by administering melatonin receptor antagonists to female white-footed mice and then measuring plasma melatonin concentrations. In the first experiment, we observed that luzindole, a dual MT1/MT2 receptor antagonist administered 1h after lights off, caused an increase in plasma melatonin both 1 and 2h later. In a second experiment, we did not observe a change in melatonin concentrations following injection of an antagonist specific for the MT2 subtype. These results suggest the possibility of feedback control of melatonin release, occurring preferentially through the MT1 receptor subtype. PMID:23528860

  2. Pineal melatonin synthesis in Syrian hamsters: A summary

    NASA Astrophysics Data System (ADS)

    Rollag, M. D.

    1982-12-01

    During the past decade there has been ample documentation of the proposition that the pineal gland mediates photoperiodic influences upon reproductive behavior of hamsters. It is commonly hypothesized that the pineal gland expresses its activity by transformation of photoperiodic information into an hormonal output, that hormone being melatonin. If this hypothesis is correct, there must be some essential diffrence in melatonin's output when hamsters are exposed to different photoperiodic environments. The experiments summarized in this communication analyze pineal melatonin contents in Syrian hamsters maintained in a variety of photoperiodic conditions during different physiological states. The results demonstrate that adult hamsters have a daily surge in pineal melatonin content throughout their lifetime when exposed to simulated annual photoperiodic cycles. There is some fluctuation in the amount of pineal melatonin produced during different physiological states and photoperiodic environments, but these fluctuations seem small when compared to those normally found for other regulatory hormones. When hamsters are exposed to different photoperiodic regimens, the daily melatonin surge maintains a relatively constant phase relationship with respect to the onset of daily activity. There is a concomitant change in its phase relationship with respect to light-dark transitions.

  3. Posttranscriptional regulation of pineal melatonin synthesis in Octodon degus.

    PubMed

    Lee, Soo Jung; Liu, Tiecheng; Chattoraj, Asamanja; Zhang, Samantha L; Wang, Lijun; Lee, Theresa M; Wang, Michael M; Borjigin, Jimo

    2009-08-01

    Small laboratory animals have provided significant information about melatonin regulation, yet most of these organisms are nocturnal and regulate melatonin synthesis by mechanisms that diverge from those of humans. For example, in all rodents examined, melatonin secretion occurs with a time lag of several hours after the onset of darkness; in addition, arylalkylamine N-acetyltransferase (AANAT), the key enzyme in melatonin synthesis, displays dynamic transcriptional activation specifically at night in all rodents studied to date. In ungulates and primates including humans, on the other hand, melatonin secretion occurs immediately during the early night and is controlled by circadian posttranscriptional regulation of AANAT. We hypothesize that the diurnal Octodon degus (an Hystricognath rodent) could serve as an improved experimental model for studies of human melatonin regulation. To test this, we monitored melatonin production in degus using pineal microdialysis and characterized the regulation of melatonin synthesis by analyzing degu Aanat. Degu pineal melatonin rises with little latency at night, as in ungulates and primates. In addition, degu Aanat mRNA expression displays no detectable diurnal variation, suggesting that, like ungulates and primates, melatonin in this species is regulated by a posttranscriptional mechanism. Compared with AANAT from all rodents examined to date, the predicted amino acid sequence of degu AANAT is phylogenetically more closely related to ungulate and primate AANAT. These data suggest that Octodon degus may provide an ideal model system for laboratory investigation of mechanisms of melatonin synthesis and secretion in diurnal mammals.

  4. Decreased melatonin biosynthesis, calcium flux, pineal gland calcification and aging: a hypothetical framework.

    PubMed

    Schmid, H A

    1993-01-01

    Increased pineal calcifications and decreased pineal melatonin biosynthesis, both age related, support the notion of a pineal bio-organic timing mechanism. Decreased calcium ion availability is the single common denominator of diminished beta-postreceptor- and alpha-receptor-stimulating functions in beta-receptor potentiation, which is necessary for nocturnal peak melatonin production. A comprehensive framework for the interaction of aging pineal cell mechanisms, calcium flux and melatonin biosynthesis is presented. PMID:8244046

  5. A new concept for melatonin deficit: on pineal calcification and melatonin excretion.

    PubMed

    Kunz, D; Schmitz, S; Mahlberg, R; Mohr, A; Stöter, C; Wolf, K J; Herrmann, W M

    1999-12-01

    Even though exogenous melatonin has proven to influence sleep and circadian parameters, low endogenous melatonin is not related to sleep disturbances, nor does it predict response to melatonin replacement therapy. In this manuscript, we present a new concept towards a definition of a melatonin deficit. The purpose of the study was to introduce a marker for an intra-individual decrease in melatonin production. Therefore, we developed a method to quantify the degree of pineal calcification (DOC) using cranial computed tomography. Combining pineal DOC with the organs's size, we estimated the uncalcified pineal gland volume. This estimation was positively and significantly associated with 6-sulfatoxymelatonin (aMT6s), collected over 24 hours in urine, in 26 subjects. Data yielded evidence that the decline in aMT6s excretion with age can be sufficiently explained by an increased pineal calcification. These results suggest that DOC might be useful as an indicator of an intra-individual, decreased capability of the pineal gland to produce melatonin. DOC might prove to be a response-marker for melatonin replacement therapy and a vulnerability marker of the circadian timing system. PMID:10633482

  6. Leptin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland.

    PubMed

    Peliciari-Garcia, Rodrigo Antonio; Andrade-Silva, Jéssica; Cipolla-Neto, José; Carvalho, Carla Roberta de Oliveira

    2013-01-01

    Pineal melatonin synthesis can be modulated by many peptides, including insulin. Because melatonin appears to alter leptin synthesis, in this work we aimed to investigate whether leptin would have a role on norepinephrine- (NE-)mediated melatonin synthesis in cultured rat pineal glands. According to our data, cultured rat pineal glands express leptin receptor isoform b (Ob-Rb). Pineal expression of Ob-Rb mRNA was also observed in vivo. Administration of leptin (1 nM) associated with NE ( 1 µM) reduced melatonin content as well as arylalkylamine-N-acetyl transferase (AANAT) activity and expression in cultured pineal glands. Leptin treatment per se induced the expression of STAT3 in cultured pineal glands, but STAT3 does not participate in the leptin modulation of NE-mediated pineal melatonin synthesis. In addition, the expression of inducible cAMP early repressor (ICER) was further induced by leptin challenge when associated with NE. In conclusion, leptin inhibition of pineal melatonin synthesis appears to be mediated by a reduction in AANAT activity and expression as well as by increased expression of Icer mRNA. Peptidergic signaling within the pineal gland appears to be one of the most important signals which modulates melatonin synthesis; leptin, as a member of this system, is not an exception.

  7. Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland.

    PubMed

    Souza-Teodoro, Luis Henrique; Dargenio-Garcia, Letícia; Petrilli-Lapa, Camila Lopes; Souza, Ewerton da Silva; Fernandes, Pedro A C M; Markus, Regina P; Ferreira, Zulma S

    2016-03-01

    Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y1 receptors that enhance β-adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransferase (ASMT; EC 2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by β-adrenergic stimulation. ATP increased NAS levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration-dependent manner. Our results demonstrate that enhanced NAS levels, which depend on phospholipase C (PLC) activity (but not the induction of gene transcription), are a post-translational effect. By contrast, melatonin reduction is related to an ASMT inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor-kappa B (NF-kB) translocation. Neither the P2Y1 receptor activation nor the PLC-mediated pathway was involved in the decrease in melatonin, indicating that ATP regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates NAS and melatonin synthesis and point to a regulatory role for ATP as a cotransmitter in the control of ASMT, the rate-limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving ASMT regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti-inflammatory, neuroprotective, and neurogenic effects.

  8. Mechanisms regulating melatonin synthesis in the mammalian pineal organ.

    PubMed

    Schomerus, Christof; Korf, Horst-Werner

    2005-12-01

    The day/night rhythm in melatonin production is a characteristic feature in vertebrate physiology. This hormonal signal reliably reflects the environmental light conditions and is independent of behavioral aspects. In all mammalian species, melatonin production is regulated by norepinephrine, which is released from sympathetic nerve fibers exclusively at night. Norepinephrine elevates the intracellular cAMP concentration via beta-adrenergic receptors and activates the cAMP-dependent protein kinase A. This pathway is crucial for regulation of the penultimate enzyme in melatonin biosynthesis, the arylalkylamine N-acetyltransferase (AANAT); cAMP/protein kinase A may, however, act in different ways. In ungulates and primates, pinealocytes constantly synthesize AANAT protein from continually available Aanat mRNA. During the day-in the absence of noradrenergic stimulation-the protein is immediately destroyed by proteasomal proteolysis. At nighttime, elevated cAMP levels cause phosphorylation of AANAT by protein kinase A. This posttranslational modification leads to interaction of phosphorylated AANAT with regulatory 14-3-3 proteins, which protect AANAT from degradation. Increases in AANAT protein are paralleled by increases in enzyme activity. Stimulation of the cAMP/protein kinase A pathway may also activate pineal gene expression. In rodents, transcriptional activation of the Aanat gene is the primary mechanism for the induction of melatonin biosynthesis and results in marked day/night fluctuations in Aanat mRNA. It involves protein kinase A-dependent phosphorylation of the transcription factor cyclic AMP response element-binding protein (CREB) and binding of phosphorylated CREB in the promoter region of the Aanat gene. In conclusion, a common neuroendocrine principle, the nocturnal rise in melatonin, is controlled by strikingly diverse regulatory mechanisms. This diversity has emerged in the course of evolution and reflects the high adaptive plasticity of the

  9. Electrical stimulation of the hypothalamic nucleus paraventricularis mimics the effects of light on pineal melatonin synthesis

    SciTech Connect

    Olcese, J.; Reuss, S.; Steinlechner, S.

    1987-02-02

    In an attempt to clarify further the role of the hypothalamic paraventricular nuclei (PVN) in the control of pineal function, the effects of 2 min electrical stimulation of these nuclei were investigated in acutely blinded, adult, male Sprague-Dawley rats. Pineal serotonin-N-acetyltransferase (NAT) activity, melatonin content and catecholamine levels were measured by means of radio-enzymatic, radioimmunoassay and high-performance liquid-chromatography methods, respectively. All three pineal parameters underwent significant declines following brief PVN stimulation during the night time. These observations lend credence to the view that the neural pathways transmitting light information to the sympathetic innervation controlling pineal melatonin synthesis. 22 references, 1 figure.

  10. Effect of electric field exposure on melatonin and enzyme circadian rhythms in the rat pineal

    SciTech Connect

    Wilson, B.; Anderson, L.E.; Hilton, D.I.; Phillips, R.D.

    1980-11-01

    The effects of chronic 30-day electric field exposure on pineal serotonin N-acetyl transferase (EC 2.1.15) activity as well as melatonin and 5-methoxy tryptophol (5-MTOL) concentrations in rats, were assessed.

  11. Melatonin

    MedlinePlus

    ... may be used in these pills: natural and synthetic (manmade). Natural melatonin is made from the pineal ... a virus so it is not recommended. The synthetic form of melatonin does not carry this risk. ...

  12. The role of pineal gland and exogenous melatonin on the irradiation stress response of suprarenal gland.

    PubMed

    Alicelebić, Selma; Mornjaković, Zakira; Susko, Irfan; Cosović, Esad; Beganović-Petrović, Amira

    2006-11-01

    Pineal gland has and antistressogenic role. Its main hormone, melatonin, has radio protective effect on endocrine and other dynamic tissues. In our previous study, we have shown that pinealectomy changes the behavior of suprarenal gland in totally irradiated rats. The aim of this study is to evaluate the effect of exogenous melatonin on suprarenal gland of rats with or without pineal gland. Four months after pinealectomy (experimental group) or shampinealectomy (control group), adult Wistar male rats were daily treated with 0,2 mg of melatonin intraperitoneally, during two weeks. Thereafter, all animals were totally irradiated with 8 Gy of Gamma rays produced from Cobalt 60. Animals who survived were sacrificed on the 17(th) post irradiation day. Qualitative and quantitative characteristics of the suprarenal gland were studied using histological methods. The results show that exogenous melatonin had protective role on suprarenal gland in totally irradiated rats and that those effects were more pronounced in the presence of pineal gland.

  13. Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland.

    PubMed

    Garcia, Rodrigo Antonio Peliciari; Afeche, Solange Castro; Scialfa, Julieta Helena; do Amaral, Fernanda Gaspar; dos Santos, Sabrina Heloísa José; Lima, Fabio Bessa; Young, Martin Elliot; Cipolla-Neto, José

    2008-01-01

    The mammalian pineal gland synthesizes melatonin in a circadian manner, peaking during the dark phase. This synthesis is primarily regulated by sympathetic innervations via noradrenergic fibers, but is also modulated by many peptidergic and hormonal systems. A growing number of studies reveal a complex role for melatonin in influencing various physiological processes, including modulation of insulin secretion and action. In contrast, a role for insulin as a modulator of melatonin synthesis has not been investigated previously. The aim of the current study was to determine whether insulin modulates norepinephrine (NE)-mediated melatonin synthesis. The results demonstrate that insulin (10(- 8)M) potentiated norepinephrine-mediated melatonin synthesis and tryptophan hydroxylase (TPOH) activity in ex vivo incubated pineal glands. When ex vivo incubated pineal glands were synchronized (12h NE-stimulation, followed by 12h incubation in the absence of NE), insulin potentiated NE-mediated melatonin synthesis and arylalkylamine-N-acetyltransferase (AANAT) activity. Insulin did not affect the activity of hydroxyindole-O-methyltranferase (HIOMT), nor the gene expression of tpoh, aanat, or hiomt, under any of the conditions investigated. We conclude that insulin potentiates NE-mediated melatonin synthesis in cultured rat pineal gland, potentially through post-transcriptional events.

  14. Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats.

    PubMed

    Benova, Miroslava; Herichova, Iveta; Stebelova, Katarina; Paulis, Ludovit; Krajcirovicova, Kristina; Simko, Fedor; Zeman, Michal

    2009-04-01

    Melatonin plays a role in blood pressure (BP) control. The aim of this study was to determine whether melatonin concentrations and melatonin receptor levels are altered in L-NAME-treated, NO-deficient hypertensive rats. Two groups of male adult Wistar rats were investigated: rats (n=36) treated with NO-synthase inhibitor L-NAME (40 mg kg(-1)) and age-matched controls (n=36). BP was measured weekly by tail-cuff plethysmography. After 4 weeks, L-NAME administration increased BP (178+/-1 vs. control 118+/-1 mm Hg). At the end of treatment, rats were killed in regular 4 h intervals over a 24-h period. Melatonin concentrations in the plasma, pineal gland, heart and kidney and melatonin receptor (MT(1)) density in the aorta were determined. A significant daily rhythm of melatonin concentrations was found in the blood, pineal gland, kidney and heart of both control and hypertensive rats. Peak nighttime pineal melatonin concentrations were higher in L-NAME-treated rats than in controls (3.38+/-0.48 vs. 1.75+/-0.33 ng per pineal gland). No differences between both groups were found in melatonin concentrations in blood, kidney and heart or in the MT(1) receptor density in the aorta. Our results suggest that L-NAME treatment enhances melatonin production in the pineal gland, potentially by decreasing an inhibitory effect of NO on melatonin production in the pineal gland. However, the enhanced pineal melatonin formation was insufficient to increase melatonin concentrations in circulation, heart and kidney of L-NAME-treated rats, indicating an increased use of melatonin in hypertensive animals.

  15. 60-Hz electric-field effects on pineal melatonin rhythms: time course for onset and recovery

    SciTech Connect

    Wilson, B.W.; Chess, E.K.; Anderson, L.E.

    1986-01-01

    Rats exposed for 3 weeks to uniform 60-Hz electric fields of 39 kV/m (effective field strength) failed to show normal pineal gland circadian rhythms in serotonin N-acetyl transferase activity and melatonin concentrations. The time required for recovery of the melatonin rhythm after cessation of field exposure was determined to be less than 3 days. The rapid recovery suggests that the overall metabolic competence of the pineal is not permanently compromised by electric-field exposure, and that the circadian rhythm effect may be neuronally mediated.

  16. Stress inhibition of melatonin synthesis in the pineal organ of rainbow trout (Oncorhynchus mykiss) is mediated by cortisol.

    PubMed

    López-Patiño, Marcos A; Gesto, Manuel; Conde-Sieira, Marta; Soengas, José L; Míguez, Jesús M

    2014-04-15

    Cortisol has been suggested to mediate the effect of stress on pineal melatonin synthesis in fish. Therefore, we aimed to determine how pineal melatonin synthesis is affected by exposing rainbow trout to different stressors, such as hypoxia, chasing and high stocking density. In addition, to test the hypothesis that cortisol is a mediator of such stress-induced effects, a set of animals were intraperitoneally implanted with coconut oil alone or containing cortisol (50 mg kg(-1) body mass) and sampled 5 or 48 h post-injection at midday and midnight. The specificity of such effect was also assessed in cultured pineal organs exposed to cortisol alone or with the general glucocorticoid receptor antagonist, mifepristone (RU486). Stress (in particular chasing and high stocking density) affected the patterns of plasma and pineal organ melatonin content during both day and night, with the greatest reduction occurring at night. The decrease in nocturnal melatonin levels in the pineal organ of stressed fish was accompanied by increased serotonin content and decreased AANAT2 enzymatic activity and mRNA abundance. Similar effects on pineal melatonin synthesis to those elicited by stress were observed in trout implanted with cortisol for either 5 or 48 h. These data indicate that stress negatively influences the synthesis of melatonin in the pineal organ, thus attenuating the day-night variations of circulating melatonin. The effect might be mediated by increased cortisol, which binds to trout pineal organ-specific glucocorticoid receptors to modulate melatonin rhythms. Our results in cultured pineal organs support this. Considering the role of melatonin in the synchronization of daily and annual rhythms, the results suggest that stress-induced alterations in melatonin synthesis could affect the availability of fish to integrate rhythmic environmental information.

  17. Nocturnal headache associated with melatonin deficiency due to a pineal gland cyst.

    PubMed

    Karadaş, Omer; Ipekdal, Ilker H; Ulaş, Umit H; Odabaşi, Zeki

    2012-02-01

    The cyclic nature of some of headache disorders is closely related to melatonin, which is secreted by the pineal gland. We report a 29-year-old male patient with a 2.5-year history of headaches that woke him in the middle of the night. These headaches were pulsatile and continued until sunrise. During these attacks he also suffered from allodynia over the scalp, bilateral conjunctival hyperemia, and nervousness. His brain MRI showed a 5mm by 4mm neuroepithelial cyst in the pineal gland. The peak plasma melatonin level that was measured at 2 am was 28 pg/mL. The patient underwent oral melatonin treatment (6 mg/day). After 1 month he experienced a 70% reduction in his symptoms. When the melatonin dosage was increased to 10mg/day he became headache-free, and 5 months after the treatment began, had no complaints. His 5-month follow-up plasma melatonin level at 2 am was 61 pg/mL. To our knowledge this is the first report of a patient with nocturnal headache associated with a low level of melatonin due to a neuroepithelial cyst in the pineal gland.

  18. Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mammalian pineal gland synthesizes melatonin in a circadian manner, peaking during the dark phase. This synthesis is primarily regulated by sympathetic innervations via noradrenergic fibers, but is also modulated by many peptidergic and hormonal systems. A growing number of studies reveal a comp...

  19. Pineal oscillator functioning in the chicken--effect of photoperiod and melatonin.

    PubMed

    Turkowska, Elzbieta; Majewski, Pawel M; Rai, Seema; Skwarlo-Sonta, Krystyna

    2014-02-01

    The avian pineal gland, apart from the hypothalamic master clock (suprachiasmatic nuclei, SCN) and retina, functions as an independent circadian oscillator, receiving external photic cues that it translates into the rhythmical synthesis of melatonin, a biochemical signal of darkness. Functional similarity to the mammalian SCN makes the avian pineal gland a convenient model for studies on biological clock mechanisms in general. Pineal melatonin is produced not only in a light-dependent manner but also remains under the control of the endogenous oscillator, while the possible involvement of melatonin in maintaining cyclic expression of the avian clock genes remains to be elucidated. The aim of the present study was to characterize the diurnal profiles of main clock genes transcription in the pineal glands of chickens exposed to continuous light (LL) and supplemented with exogenous melatonin. We hypothesized that rearing chickens from the day of hatch under LL conditions would evoke a functional pinealectomy, influencing, in turn, pineal clock function. To verify this hypothesis, we examined the diurnal transcriptional profiles of selected clock genes as well as the essential parameters of pineal gland function: transcription of the genes encoding arylalkylamine N-acetyltransferase (Aanat), a key enzyme in melatonin biosynthesis, and the melatonin receptor (Mel1c), along with the blood melatonin level. Chickens hatched in summer or winter were maintained under LD 16:8 and 8:16, corresponding to the respective photoperiods, as the seasonal control groups. Another set of chickens was kept in parallel under LL conditions and some were supplemented with melatonin to check the ability of exogenous hormone to antagonize the effects evoked by continuous light. Twelve-day-old chickens were sacrificed every 3 h over a 24-h period and the mRNAs of selected clock genes, Bmal1, Cry1, Per3, E4bp4, together with those of Aanat and Mel1c, were quantified in the isolated pineal

  20. Changes in plasma melatonin levels and pineal organ melatonin synthesis following acclimation of rainbow trout (Oncorhynchus mykiss) to different water salinities.

    PubMed

    López-Patiño, Marcos A; Rodríguez-Illamola, Arnau; Gesto, Manuel; Soengas, José L; Míguez, Jesús M

    2011-03-15

    Melatonin has been suggested to play a role in fish osmoregulation, and in salmonids has been related to the timing of adaptive mechanisms during smolting. It has been described that acclimation to different environmental salinities alters levels of circulating melatonin in a number of fish species, including rainbow trout. However, nothing is known regarding salinity effects on melatonin synthesis in the pineal organ, which is the main source of rhythmically produced and secreted melatonin in blood. In the present study we have evaluated, in rainbow trout, the effects of acclimation to different salinities on day and night plasma melatonin values and pineal organ melatonin synthesis. Groups of freshwater (FW)-adapted rainbow trout were placed in tanks with four different levels of water salinity (FW, 6, 12, 18 p.p.t.; parts per thousand) and maintained for 6 h or 5 days. Melatonin content in plasma and pineal organs, as well as the pineal content of serotonin (5-HT) and its main oxidative metabolite (5-hydroxyindole-3-acetic acid; 5-HIAA) were measured by high performance liquid chromatography. In addition, day-night changes in pineal organ arylalkylamine N-acetyltransferase (AANAT2) activity and aanat2 gene expression were studied. Plasma osmolalities were found to be higher in rainbow trout exposed to all salinity levels compared with the control FW groups. A salinity-dependent increase in melatonin content was found in both plasma and pineal organs. This effect was observed during the night, and was related to an increase in aanat2 mRNA abundance and AANAT2 enzyme activity, both of which also occurred during the day. Also, the levels of indoles (5-HT, 5-HIAA) in the pineal organ were negatively affected by increasing water salinity, which seems to be related to the higher recruitment of 5-HT as a substrate for the increased melatonin synthesis. A stimulatory effect of salinity on pineal aanat2 mRNA expression was also identified. These results indicate that

  1. Homeobox genes and melatonin synthesis: regulatory roles of the cone-rod homeobox transcription factor in the rodent pineal gland.

    PubMed

    Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production.

  2. Homeobox Genes and Melatonin Synthesis: Regulatory Roles of the Cone-Rod Homeobox Transcription Factor in the Rodent Pineal Gland

    PubMed Central

    Rath, Martin Fredensborg

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production. PMID:24877149

  3. Interleukin-1 β Modulates Melatonin Secretion in Ovine Pineal Gland: Ex Vivo Study.

    PubMed

    Herman, A P; Bochenek, J; Skipor, J; Król, K; Krawczyńska, A; Antushevich, H; Pawlina, B; Marciniak, E; Tomaszewska-Zaremba, D

    2015-01-01

    The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1β, on melatonin release and expression enzymes essential for this hormone synthesis: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) in ovine pineal gland, taking into account the immune status of animals before sacrificing. Ewes were injected by lipopolysaccharide (LPS; 400 ng/kg) or saline, two hours after sunset during short day period (December). Animals were euthanized three hours after the injection. Next, the pineal glands were collected and divided into four explants. The explants were incubated with (1) medium 199 (control explants), (2) norepinephrine (NE; 10 µM), (3) IL-1β (75 pg/mL), or (4) NE + IL-1β. It was found that IL-1β abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1β also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1β treatment on gene expression of HIOMT; however, the pineal fragments isolated from LPS-treated animals were characterized by elevated (P < 0.05) expression of HIOMT mRNA and protein compared to the explants from saline-treated ewes. Our study proves that IL-1β suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression.

  4. Interleukin-1β Modulates Melatonin Secretion in Ovine Pineal Gland: Ex Vivo Study

    PubMed Central

    Herman, A. P.; Bochenek, J.; Skipor, J.; Król, K.; Krawczyńska, A.; Antushevich, H.; Pawlina, B.; Marciniak, E.; Tomaszewska-Zaremba, D.

    2015-01-01

    The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1β, on melatonin release and expression enzymes essential for this hormone synthesis: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) in ovine pineal gland, taking into account the immune status of animals before sacrificing. Ewes were injected by lipopolysaccharide (LPS; 400 ng/kg) or saline, two hours after sunset during short day period (December). Animals were euthanized three hours after the injection. Next, the pineal glands were collected and divided into four explants. The explants were incubated with (1) medium 199 (control explants), (2) norepinephrine (NE; 10 µM), (3) IL-1β (75 pg/mL), or (4) NE + IL-1β. It was found that IL-1β abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1β also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1β treatment on gene expression of HIOMT; however, the pineal fragments isolated from LPS-treated animals were characterized by elevated (P < 0.05) expression of HIOMT mRNA and protein compared to the explants from saline-treated ewes. Our study proves that IL-1β suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression. PMID:26339621

  5. [Melatonin radioimmunoanalysis: evaluation of the pineal function in hyperprolactinemic male rats and controls].

    PubMed

    Villanúa, M A; Esquifino, A I; Tresguerres, J A

    1986-06-01

    A sensitive and specific radioimmunoassay for melatonin quantification in rat pineal and biological fluids is described. The assay utilizes a specific antibody and H3-melatonin as tracer. Bound and free fraction were separated by a saturated sulphate ammonium solution. The sensitivity of the method is 9 pg/ml. The intra and interassay variation coefficient were 10.4 and 13.6% respectively. By means of this RIA the content of melatonin in the pineal gland in male rats made hyperprolactinemic on day 30 of life and their respective sham-operated controls has been evaluated. The results showed that the melatonin content measured at 2 a.m. was reduced in the transplanted animals when compared to control group, not only shortly (48 hours) after the transplant operation, but also in the chronic situation; though suggesting that further investigations are necessary to deepen and understand the interrelationships between prolactin and pineal gland and their effect on the hypothalamic-pituitary-gonadal axis.

  6. Structural and functional evolution of the pineal melatonin system in vertebrates.

    PubMed

    Falcón, Jack; Besseau, Laurence; Fuentès, Michael; Sauzet, Sandrine; Magnanou, Elodie; Boeuf, Gilles

    2009-04-01

    In most species daily rhythms are synchronized by the photoperiodic cycle. They are generated by the circadian system, which is made of a pacemaker, an entrainment pathway to this clock, and one or more output signals. In vertebrates, melatonin produced by the pineal organ is one of these outputs. The production of this time-keeping hormone is high at night and low during the day. Despite the fact that this is a well-preserved pattern, the pathways through which the photoperiodic information controls the rhythm have been profoundly modified from early vertebrates to mammals. The photoperiodic control is direct in fish and frogs and indirect in mammals. In the former, full circadian systems are found in photoreceptor cells of the pineal organ, retina, and possibly brain, thus forming a network where melatonin could be a hormonal synchronizer. In the latter, the three elements of a circadian system are scattered: the photoreceptive units are in the eyes, the clocks are in the suprachiasmatic nuclei of the hypothalamus, and the melatonin-producing units are in the pineal cells. Intermediate situations are observed in sauropsids. Differences are also seen at the level of the arylalkylamine N-acetyltransferase (AANAT), the enzyme responsible for the daily variations in melatonin production. In contrast to tetrapods, teleost fish AANATs are duplicated and display tissue-specific expression; also, pineal AANAT is special--it responds to temperature in a species-specific manner, which reflects the fish ecophysiological preferences. This review summarizes anatomical, structural, and molecular aspects of the evolution of the melatonin-producing system in vertebrates. PMID:19456332

  7. Amyloid β peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway.

    PubMed

    Cecon, Erika; Chen, Min; Marçola, Marina; Fernandes, Pedro A C; Jockers, Ralf; Markus, Regina P

    2015-06-01

    Melatonin is the hormone produced by the pineal gland known to regulate physiologic rhythms and to display immunomodulatory and neuroprotective properties. It has been reported that Alzheimer disease patients show impaired melatonin production and altered expression of the 2 G protein-coupled melatonin receptors (MTRs), MT₁ and MT₂, but the underlying mechanisms are not known. Here we evaluated whether this dysfunction of the melatonergic system is directly caused by amyloid β peptides (Aβ(1-40) and Aβ(1-42)). Aβ treatment of rat pineal glands elicited an inflammatory response within the gland, evidenced by the up-regulation of 52 inflammatory genes, and decreased the production of melatonin up to 75% compared to vehicle-treated glands. Blocking NF-κB activity prevented this effect. Exposure of HEK293 cells stably expressing recombinant MT₁ or MT₂ receptors to Aβ lead to a 40% reduction in [(125)I]iodomelatonin binding to MT₁. ERK1/2 activation triggered by MTRs, but not by the β₂-adrenergic receptor, was markedly impaired by Aβ in HEK293 transfected cells, as well as in primary rat endothelial cells expressing endogenous MTRs. Our data reveal the melatonergic system as a new target of Aβ, opening new perspectives to Alzheimer disease diagnosis and therapeutic intervention.

  8. Melatonin rhythm onset in the adult siberian hamster: influence of photoperiod but not 60-Hz magnetic field exposure on melatonin content in the pineal gland and in circulation.

    PubMed

    Yellon, S M; Truong, H N

    1998-02-01

    To determine the relationship between pineal melatonin production and its appearance in circulation, the rising phase of the pineal and serum melatonin rhythm was studied in the adult Siberian hamster. Melatonin concentrations increased in the pineal gland and in serum at 1.50 and 1.75 h, respectively, relative to lights off in long days (16 h of light/day) and at 2.00 and 2.75 h, respectively, in short days (10 h of light/day). Thus, a photoperiod-dependent melatonin rise in circulation lagged production by the pineal gland by 0.50 h--a delay of 0.75 h in short-day hamsters versus 0.25 h in long-day hamsters. Following initiation of this rise, concentrations that were typical of the nighttime peak were achieved within 2 h of melatonin rhythm onset, regardless of photoperiod. To determine whether clock control of the rising phase of the melatonin rhythm, in the absence of photoperiod cues, may be disrupted by perturbations in the ambient magnetic field, hamsters in constant darkness were acutely exposed to a 1-Gauss, 60-Hz magnetic field for 15 min or were daily exposed to this treatment for 14 or 21 days. Neither the melatonin rise in pineal content or circulation during subjective night was affected by acute or chronic magnetic field exposures; testes regression similarly occurred in sham and daily magnetic field-exposed hamsters in constant darkness. These findings indicate that magnetic field exposures are unlikely to serve as a zeitgeber for the circadian mechanism that controls onset of the melatonin rhythm; rather, photoperiod is a predominant cue that may differentially regulate the rising phase of melatonin production in the pineal gland and concentration in circulation.

  9. Regulation of melatonin secretion in the pineal organ of the domestic duck--an in vitro study.

    PubMed

    Prusik, M; Lewczuk, B; Ziółkowska, N; Przybylska-Gornowicz, B

    2015-01-01

    The aim of study was to determine the mechanisms regulating melatonin secretion in the pineal organs of 1-day-old and 9-month-old domestic ducks. The pineals were cultured in a superfusion system under different light conditions. Additionally, some explants were treated with norepinephrine. The pineal glands of 1-day-old ducks released melatonin in a well-entrained, regular rhythm during incubation under a 12 hrs light:12 hrs dark cycle and adjusted their secretory activity to a reversed 12 hrs dark:12 hrs light cycle within 2 days. In contrast, the diurnal changes in melatonin secretion from the pineals of 9-month-old ducks were largely irregular and the adaptation to a reversed cycle lasted 3 days. The pineal organs of nestling and adult ducks incubated in a continuous light or darkness secreted melatonin in a circadian rhythm. The treatment with norepinephrine during photophases of a light-dark cycle resulted in: 1) a precise adjustment of melatonin secretion rhythm to the presence of this catecholamine in the culture medium, 2) a very high amplitude of the rhythm, 3) a rapid adaptation of the pineal secretory activity to a reversed light-dark cycle. The effects of norepinephrine were similar in the pineal organs of nestlings and adults. In conclusion, melatonin secretion in the duck pineal organ is controlled by three main mechanisms: the direct photoreception, the endogenous generator and the noradrenergic transmission. The efficiency of intra-pineal, photosensitivity-based regulatory mechanism is markedly lower in adult than in nestling individuals.

  10. [Influence of pineal hormone melatonin on behavioral disturbances and neurological status of animals after hemorrhagic stroke].

    PubMed

    Arushanian, E B; Naumov, S S

    2011-01-01

    Experimental hemorrhagic stroke causes behavior and locomotor activity with memory impairment and neurological disturbances in rats. These shifts are weaker in the evening hours than after morning testing. The repeated administration of the pineal gland hormone melatonin (melaxen) during one week significantly decreases behavior and neurological deficits as well as pathomorphological signs in the lesion focus. The normalizing effect of the hormone is more distinct in the evening.

  11. The anti-tumor activity of pineal melatonin and cancer enhancing life styles in industrialized societies.

    PubMed

    Bartsch, Christian; Bartsch, Hella

    2006-05-01

    This review discusses the potential role of the anti-tumor activity of pineal melatonin for the aetiology and prevention of cancers related to life-styles in industrialized societies, e.g. frequent long-distance flights as well as chronic night shift work leading to circadian disturbances of neuroendocrine parameters including melatonin. Experimental studies show that melatonin controls not only the growth of well-differentiated cancers, but also possesses anti-carcinogenic properties. Therefore, it is plausible that disturbances of circadian melatonin rhythmicity could be functionally involved in elevated cancer risks among aircrew members and nurses frequently working on night shifts. Due to the suppression of melatonin by light it can be assumed that too much artificial light at night could, at least in part, be responsible for generally increasing rates of e.g. breast cancer in industrialized countries. It is discussed under which conditions a transient substitutional therapy with melatonin could be justified or which forms of living could help to physiologically foster melatonin secretion to optimise control over cancerous growth and development.

  12. Critical time delay of the pineal melatonin rhythm in humans due to weak electromagnetic exposure.

    PubMed

    Halgamuge, Malka N

    2013-08-01

    Electromagnetic fields (EMFs) can increase free radicals, activate the stress response and alter enzyme reactions. Intracellular signalling is mediated by free radicals and enzyme kinetics is affected by radical pair recombination rates. The magnetic field component of an external EMF can delay the "recombination rate" of free radical pairs. Magnetic fields thus increase radical life-times in biological systems. Although measured in nanoseconds, this extra time increases the potential to do more damage. Melatonin regulates the body's sleep-wake cycle or circadian rhythm. The World Health Organization (WHO) has confirmed that prolonged alterations in sleep patterns suppress the body's ability to make melatonin. Considerable cancer rates have been attributed to the reduction of melatonin production as a result of jet lag and night shift work. In this study, changes in circadian rhythm and melatonin concentration are observed due to the external perturbation of chemical reaction rates. We further analyze the pineal melatonin rhythm and investigate the critical time delay or maturation time of radical pair recombination rates, exploring the impact of the mRNA degradation rate on the critical time delay. The results show that significant melatonin interruption and changes to the circadian rhythm occur due to the perturbation of chemical reaction rates, as also reported in previous studies. The results also show the influence of the mRNA degradation rate on the circadian rhythm's critical time delay or maturation time. The results support the hypothesis that exposure to weak EMFs via melatonin disruption can adversely affect human health.

  13. Melatonin and pineal gland peptides are able to correct the impairment of reproductive cycles in rats.

    PubMed

    Arutjunyan, Alexander; Kozina, Ljudmila; Milyutina, Yulia; Korenevsky, Andrew; Stepanov, Michael; Arutyunov, Vladimir

    2012-12-01

    Catecholamines play an important role in the hypothalamic regulation of the synthesis and secretion of gonadotropin- releasing hormone, or gonadoliberin. We have shown that melatonin and the pineal gland peptides (epithalamine and epitalon) exert a correcting influence on the diurnal dynamics of norepinephrine (NE) in the medial preoptic area (MPA) and of dopamine (DA) in the median eminence with arcuate nuclei (ME-Arc) disturbed by single administration of the neurotoxic xenobiotic 1,2-dimethylhydrazine (DMH) in female rats. It has been found that experiments with DMH administration can be used as an animal model of female reproductive system premature aging. The investigation of epithalamine (a polypeptide preparation from the bovine pineal gland) effect on circadian rhythms disturbed by the neurotoxic compound DMH has shown a recovery of the diurnal dynamics of NE in MPA. In addition, NE was found to decrease from 9:30 till 11 o'clock, Circadian Time (CT), which was typical of control animals. Epitalon (Ala-Glu-Asp-Gly) proved to be more effective in ME-Arc. This peptide prevents the xenobiotic caused disturbance of DA diurnal rhythm, keeping this metabolite low at 5 o'clock (CT) with it having increased by 11 o'clock (CT). The data obtained suggest that the pineal gland is important for the circadian signal normalization needed for gonadoliberin surge on the day of proestrus. Melatonin and peptides of the pineal gland can be considered as effective protectors of female reproductive system from xenobiotics and premature aging.

  14. Cysteamine effects on somatostatin, catecholamines, pineal NAT and melatonin in rats

    SciTech Connect

    Webb, S.M.; Champney, T.H.; Steger, R.W.; Vaughan, M.K.; Reiter, R.J.

    1986-03-01

    The thiol reagent cysteamine was administered to adult male rats with the aim of investigating its effect on different neural and pineal components. As expected, immunoreactive somatostatin decreased in the median eminence (ME) (p less than 0.05) and gastric antrum (p less than 0.05) after cysteamine; however, no significant change was observed in the pineal IRS content after drug treatment. A decrease in norepinephrine was observed in the ME (p less than 0.001), hypothalamus (p less than 0.001) and pineal gland (p less than 0.05), together with a rise in ME (p less than 0.005) and hypothalamic dopamine (p less than 0.005) content; these results are consistent with a dopamine-beta-hydroxylase inhibiting effect of cysteamine. No effect was observed on hypothalamic serotonin and 5-hydroxyindole-acetic acid content. Pineal N-acetyltransferase (NAT) activity was significantly higher (p less than 0.05) after cysteamine than after saline, but no statistically significant effect was observed on pineal melatonin content. The mechanism involved in the NAT rise is presumably not related to the known stimulatory effect of norepinephrine, which fell after cysteamine. It is suggested that cysteamine may act at an intracellular level, inhibiting NAT degradation, an effect demonstrated in vitro and thought to be related to a thiol:disulfide exchange mechanism.

  15. Calcium, calcification, and melatonin biosynthesis in the human pineal gland: a postmortem study into age-related factors.

    PubMed

    Schmid, H A; Requintina, P J; Oxenkrug, G F; Sturner, W

    1994-05-01

    It is believed that pineal calcification may be age-associated and that the well-demonstrated age-related decline in melatonin biosynthesis may be an expression of an alteration in calcium homeostasis in the pinealocyte. Prior correlations of melatonin to calcium deposition and age were made on the basis of radiological or semiquantitative analysis. In this postmortem study of 33 subjects (age range 3 months to 65 years) calcium deposits measured by atomic absorption spectrometry correlated positively with age in day and night samples (day: r = 0.56, P < 0.05; night: r = 0.818, P < 0.001). Nighttime (2200 h to 0800 h) pineal melatonin content (HPLC fluorometry) was higher than daytime melatonin levels (nighttime 3.80 +/- 0.3 vs. daytime 0.85 +/- 0.4 ng/mg protein). Nighttime calcium levels in the supernatant correlated negatively with melatonin content (r = -0.59, P < 0.05). PMID:7807371

  16. Genetic, temporal and developmental differences between melatonin rhythm generating systems in the teleost fish pineal organ and retina.

    PubMed

    Falcón, J; Gothilf, Y; Coon, S L; Boeuf, G; Klein, D C

    2003-04-01

    Complete melatonin rhythm generating systems, including photodetector, circadian clock and melatonin synthesis machinery, are located within individual photoreceptor cells in two sites in Teleost fish: the pineal organ and retina. In both, light regulates daily variations in melatonin secretion by controlling the activity of arylalkylamine N-acetyltransferase (AANAT). However, in each species examined to date, marked differences exist between the two organs which may involve the genes encoding the photopigments, genes encoding AANAT, the times of day at which AANAT activity and melatonin production peak and the developmental schedule. We review the fish pineal and retinal melatonin rhythm generating systems and consider the evolutional pressures and other factors which led to these differences.

  17. Role for the pineal and melatonin in glucose homeostasis: pinealectomy increases night-time glucose concentrations.

    PubMed

    la Fleur, S E; Kalsbeek, A; Wortel, J; van der Vliet, J; Buijs, R M

    2001-12-01

    The effects of melatonin on glucose metabolism are far from understood. In rats, the biological clock generates a 24-h rhythm in plasma glucose concentrations, with declining concentrations in the dark period. We hypothesized that, in the rat, melatonin enhances the dark signal of the biological clock, decreasing glucose concentrations in the dark period. We measured 24-h rhythms of plasma concentrations of glucose and insulin in pinealectomized rats fed ad libitum and subjected to a scheduled feeding regimen with six meals equally distributed over the light/dark cycle and compared them with previous data of intact rats. Pinealectomy dampened the amplitude of the 24-h rhythm in plasma glucose concentrations in rats fed ad libitum, and abolished it completely in rats subjected to the scheduled feeding regimen, while plasma insulin concentrations did not change under both conditions. Pinealectomy abolished the nocturnal decline in plasma glucose concentrations irrespective of whether rats were fed ad libitum or subjected to the scheduled feeding regimen. Melatonin replacement restored 24-h mean plasma glucose concentrations in pinealectomized rats that were subjected to the scheduled feeding regimen but, interestingly, it did not restore the 24-h rhythm. Melatonin treatment also resulted in higher meal-induced insulin responses, probably mediated via an increased sensitivity of the beta-cells. Taken together, our data demonstrate that the pineal hormone, melatonin, influences both glucose metabolism and insulin secretion from the pancreatic beta-cell. The present study also demonstrates that removal of the pineal gland cannot be compensated by mimicking plasma melatonin concentrations only.

  18. MicroRNAs in the pineal gland: miR-483 regulates melatonin synthesis by targeting arylalkylamine N-acetyltransferase.

    PubMed

    Clokie, Samuel J H; Lau, Pierre; Kim, Hyun Hee; Coon, Steven L; Klein, David C

    2012-07-20

    MicroRNAs (miRNAs) play a broad range of roles in biological regulation. In this study, rat pineal miRNAs were profiled for the first time, and their importance was evaluated by focusing on the main function of the pineal gland, melatonin synthesis. Massively parallel sequencing and related methods revealed the miRNA population is dominated by a small group of miRNAs as follows: ~75% is accounted for by 15 miRNAs; miR-182 represents 28%. In addition to miR-182, miR-183 and miR-96 are also highly enriched in the pineal gland, a distinctive pattern also found in the retina. This effort also identified previously unrecognized miRNAs and other small noncoding RNAs. Pineal miRNAs do not exhibit a marked night/day difference in abundance with few exceptions (e.g. 2-fold night/day differences in the abundance of miR-96 and miR-182); this contrasts sharply with the dynamic 24-h pattern that characterizes the pineal transcriptome. During development, the abundance of most pineal gland-enriched miRNAs increases; however, there is a marked decrease in at least one, miR-483. miR-483 is a likely regulator of melatonin synthesis, based on the following. It inhibits melatonin synthesis by pinealocytes in culture; it acts via predicted binding sites in the 3"-UTR of arylalkylamine N-acetyltransferase (Aanat) mRNA, the penultimate enzyme in melatonin synthesis, and it exhibits a developmental profile opposite to that of Aanat transcripts. Additionally, a miR-483 targeted antagonist increased melatonin synthesis in neonatal pinealocytes. These observations support the hypothesis that miR-483 suppresses Aanat mRNA levels during development and that the developmental decrease in miR-483 abundance promotes melatonin synthesis.

  19. Pineal melatonin and locomotor activity of rats under gradual illuminance transitions.

    PubMed

    Laakso, M L; Leinonen, L; Joutsiniemi, S L; Porkka-Heiskanen, T; Stenberg, D

    1992-10-01

    The locomotor activity and pineal melatonin patterns of adult male rats were compared under two different lighting regimes. The animals were kept 8 days under 12/12 h light/dark cycles with abrupt or slowly decreasing and increasing transitions (twilight periods about 2 h). The onsets of high activity and melatonin rise were phase-locked in the two conditions and related to about half-maximal illuminance level of the gradual dusk. The high activity of the control rats stopped 30-60 min before the abrupt light onset and the rats under the gradual lighting transitions ceased the locomotor activity at about 1 hour before the half-maximal illuminance. The melatonin peak levels were found 4 h before the abrupt lights-on time. Under the slow illuminance transitions the average melatonin peak was related to the illuminance level between maximum and minimum in the morning. Thus, both the melatonin rhythm and the rest-activity rhythm under the gradual dawn and dusk were adjusted according to about half-maximal illuminances in the present conditions.

  20. Pineal melatonin is a circadian time-giver for leptin rhythm in Syrian hamsters

    PubMed Central

    Chakir, Ibtissam; Dumont, Stéphanie; Pévet, Paul; Ouarour, Ali; Challet, Etienne; Vuillez, Patrick

    2015-01-01

    Nocturnal secretion of melatonin from the pineal gland may affect central and peripheral timing, in addition to its well-known involvement in the control of seasonal physiology. The Syrian hamster is a photoperiodic species, which displays gonadal atrophy and increased adiposity when adapted to short (winter-like) photoperiods. Here we investigated whether pineal melatonin secreted at night can impact daily rhythmicity of metabolic hormones and glucose in that seasonal species. For that purpose, daily variations of plasma leptin, cortisol, insulin and glucose were analyzed in pinealectomized hamsters, as compared to sham-operated controls kept under very long (16 h light/08 h dark) or short photoperiods (08 h light/16 h dark). Daily rhythms of leptin under both long and short photoperiods were blunted by pinealectomy. Furthermore, the phase of cortisol rhythm under a short photoperiod was advanced by 5.6 h after pinealectomy. Neither plasma insulin, nor blood glucose displays robust daily rhythmicity, even in sham-operated hamsters. Pinealectomy, however, totally reversed the decreased levels of insulin under short days and the photoperiodic variations in mean levels of blood glucose (i.e., reduction and increase in long and short days, respectively). Together, these findings in Syrian hamsters show that circulating melatonin at night drives the daily rhythmicity of plasma leptin, participates in the phase control of cortisol rhythm and modulates glucose homeostasis according to photoperiod-dependent metabolic state. PMID:26074760

  1. Effects of Fusarium mycotoxins on levels of serotonin, melatonin, and 5-hydroxytryptophan in pineal cell cultures.

    PubMed

    Rimando, A M; Porter, J K

    1999-01-01

    Analysis of melatonin (MEL) in pineal cell cultures by enzyme linked immunosorbent assay showed its concentration was increased by fusaric acid (FA), a mycotoxin produced by Fusarium species and associated with toxic duck and ostrich feeds. Subsequent cell culture studies demonstrated the precursors of MEL, 5-hydroxytryptophan (5HTP) and serotonin (5HT), were also affected by FA as well as other Fusarium mycotoxins. Herein we describe a technique for the analysis of 5HTP and 5HT in pineal cell cultures using HPLC with electrochemical detection (EC), and report on the effects of FA alone and in combination with fumonisin B1 (FB1) and deoxynivalenol (DON) on the levels of these MEL precursors.

  2. Food deprivation and refeeding effects on pineal indoles metabolism and melatonin synthesis in the rainbow trout Oncorhynchus mykiss.

    PubMed

    Ceinos, Rosa M; Polakof, Sergio; Illamola, Arnau Rodríguez; Soengas, José L; Míguez, Jesús M

    2008-04-01

    The effects of food deprivation and refeeding on daily rhythms of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and melatonin contents, as well as on arylalkylamine N-acetyltransferase (AANAT) activity were evaluated in the pineal organ of rainbow trout. In addition, changes in circulating melatonin and cortisol levels were tested at one single point at day and night. Immature rainbow trout were distributed in 3 experimental groups: fish fed, fish fasted (7 days), and fish fasted for 7 days and refed for 5 days. All fish were sampled from each treatment group at different times of the day-night cycle. Pineal melatonin levels and AANAT activity showed daily variations in either fed, fasted and refed trout, displaying highest values at night. Fasted trout showed reduced melatonin content throughout the 24-h cycle, which was associated with decreased AANAT activity. Rhythms of pineal 5-HT and 5-HIAA levels were evident in all groups and were negatively correlated to melatonin in fed fish groups, but not in fasted fish. A higher content of 5-HT and 5-HIAA was observed in fasted fish during the night with no apparent changes during daytime for 5-HT and increased 5-HIAA levels. Furthermore, decreased circulating levels of melatonin were observed at midday, but not at night, in food deprived trout. Refeeding for 5 days generally counteracted the effects of food deprivation. Cortisol levels in plasma were reduced after food deprivation and remained low in refed fish. The results show that food deprivation impairs daily rhythms of melatonin content in trout pineal organ by affecting the activity of melatonin synthesizing enzymes rather than by a deficiency in substrate availability.

  3. Suppression of pineal melatonin in Peromyscus leucopus by different monochromatic wavelengths of visible and near-ultraviolet light (UV-A).

    PubMed

    Benshoff, H M; Brainard, G C; Rollag, M D; Lynch, G R

    1987-09-15

    The purpose of this study was to examine the effects of monochromatic visible and near-ultraviolet radiation (UV-A) on pineal melatonin suppression in the white-footed mouse, Peromyscus leucopus. To this end, mice were entrained to a daily cycle of 8 h of light and 16 h of darkness. During the night when pineal melatonin contents were high, mice were individually exposed for 5 min to specific wavelengths of monochromatic light (10 nm half-peak bandwidths). Control animals received the same handling conditions but no experimental exposure. Pineal glands were collected from animals 18 min after the 5 min experimental exposure and were later assayed for melatonin content. In groups of animals exposed to equal photon densities (2.64 X 10(15) photons/cm2) of either 320, 340, 360, 500, or 560 nm, mean pineal melatonin content was significantly suppressed as compared to the unexposed control animals. The 640 nm wavelength (red) at the same photon density did not suppress pineal melatonin. These experiments are the first to demonstrate light-induced suppression of pineal melatonin in Peromyscus leucopus. In addition, these data reveal a novel finding: the suppression of pineal melatonin content by ultraviolet wavelengths as low as 320 and 340 nm.

  4. The pineal gland.

    PubMed

    Paquette, H

    2000-04-01

    The pineal gland is located posterior to the midbrain and is the site of melatonin production. Research on pineal gland function in neonates is very limited. This article will discuss pineal gland development and the possible relationship between melatonin production and sudden infant death syndrome. Further research on pineal gland function is needed in order to establish its significance for the neonate.

  5. Comparison of Light Emitting Diodes (LED) and Fluorescent Light on Suppression of Pineal Melatonin in the Rat

    NASA Technical Reports Server (NTRS)

    Winget, Charles M.; Heeke, D. S.; Holley, D. C.; Mele, G.; Brainard, G. C.; Hanifin, J. P.; Rollag, M. D.; Savage, Paul D. (Technical Monitor)

    1997-01-01

    To validate a novel LED array for use in animal habitat lighting by comparing its effectiveness to cool-white fluorescent (CWF) lighting in suppressing pineal gland melatonin. Male Sprague-Dawley rats, 175-200 g, were maintained under control conditions for 2 weeks (food and water ad lib, 12L: 12D CWF, 18 uW/square cm). Dark adapted animals (animals before lights on) were exposed to 5 min of LED or CWF light of similar spectral power distribution. Two groups of rats (LED vs. CWF) were compared at 5 light intensities (100, 40, 1, 1.0, and 0. 1 lux). A control group was placed into the exposure apparatus but not exposed to light. After exposure, pineal glands were rapidly removed and assayed for melatonin by RIA. Results. The dark-exposed control groups matched with the 5 intensity groups (100, 40, 10, 1.0, and 0.1 lux) showed mean + SEM pineal melatonin values of 1167 +/- 136, 1569 +/- 126, 353 +/- 34, 650 +/- 124, and 464 +/- 85, pg/ml respectively. The corresponding CWF exposure data were 393 1 41, 365 +34, 257 +/- 13, 218 +/- 42, and 239 +/- 71 pg/ml, respectively. Corresponding LED exposure data were 439 +/- 25, 462 +/- 50, 231 +/- 6, 164 +/- 12, and 158 +/- 12 pg/ml, respectively. Rats exposed to both experimental light conditions at all illuminances studied showed significant melatonin suppression (p less than 0.01, ANOVA). In no case was the melatonin suppression induced by LED illuminance significantly different from the melatonin suppression elicited by the same intensity of CWF light. The results show that a novel LED light source can suppress pineal melatonin equal to that of a conventional CWF light source.

  6. The influence of various irradiances of artificial light, twilight, and moonlight on the suppression of pineal melatonin content in the Syrian hamster.

    PubMed

    Brainard, G C; Richardson, B A; Hurlbut, E C; Steinlechner, S; Matthews, S A; Reiter, R J

    1984-01-01

    The purpose of the present studies using artificial light was to determine how the timing and duration of exposure influence the light-induced suppression of pineal melatonin levels in hamsters. An 8-min exposure to 0.186 microW/cm2 of cool white fluorescent light caused a continued depression of pineal melatonin even when animals were returned to darkness. In addition, the pineal gland does not appear to change its sensitivity to light throughout the night. A 20-min exposure to 0.019 microW/cm2 of cool white fluorescent light did not significantly suppress pineal melatonin during any time of the melatonin peak, whereas a 20-min exposure to 0.186 microW/cm2 was capable of always suppressing melatonin. Furthermore, increasing the duration of 0.019-microW/cm2 exposure to 30, 60, 120, or 180 min does not increase the capacity of this irradiance to depress melatonin. Similar to artifical light, natural light has a variable capacity for suppressing nocturnal levels of pineal melatonin. Twilight irradiances of 0.138 microW/cm2 or less did not suppress nocturnal melatonin whereas twilight irradiances of 3.0 microW/cm2 or greater did suppress pineal melatonin. A few animals did have lower melatonin after a 40-min exposure to full moonlight during July (0.045 microW/cm2) or January (0.240 microW/cm2). However, pineal melatonin levels remained high in the majority of animals exposed to full moonlight.

  7. Season-dependent postembryonic maturation of the diurnal rhythm of melatonin biosynthesis in the chicken pineal gland.

    PubMed

    Piesiewicz, A; Kedzierska, U; Podobas, E; Adamska, I; Zuzewicz, K; Majewski, P M

    2012-11-01

    Previously, we have demonstrated that the timing of the nocturnal peak of activity of the pineal arylalkylamine-N-acetyltransferase - a key enzyme in the melatonin biosynthesis pathway - in 3-wk-old chickens kept from the day of hatch under controlled laboratory conditions (L:D 12:12) varies depending on the season of hatch (summer vs. winter). The present study was undertaken to answer the following questions: (1) are season-related differences seen in the level of transcription of genes encoding enzymes of the melatonin biosynthesis pathway? (2) Does the pineal content of the main precursor (serotonin) and the final product (melatonin) exhibit age- and season-related changes? (3) At which step in postembryonic development are these season-related variations in pineal gland function most pronounced? Male Hy-line chickens hatched in the summer or winter, from eggs laid by hens held on L:D 16:8, were kept from the day of hatch under L:D 12:12 conditions. At the age of 2, 9, or 16 d, chickens were sacrificed every 2 h over a 24-h period and their pineal glands, isolated under dim red light, were processed for the measurement of (i) the level of Aanat and Asmt (acetylserotonin O-methyltransferase) mRNAs encoding the two last enzymes involved in melatonin biosynthesis, (ii) the activity of these enzymes, and (iii) the pineal content of serotonin and melatonin. Circadian rhythmicity of all the measured parameters was evaluated by the cosinor method. The levels of Aanat mRNA, AANAT enzymatic activity, and the pineal melatonin content changed during postembryonic development in a manner that was dependent on the season of hatch. Furthermore, the diurnal profile of Asmt mRNA was elevated during the light phase. In "winter" birds, the pattern and amplitude of the diurnal rhythm of accumulation of this transcript did not change with age, while in "summer" birds it increased in an age-related way. In contrast, the enzymatic activity of hydroxyindole-O-methyltransferase (HIOMT

  8. Melatonin Synthesis: Acetylserotonin O-Methyltransferase (ASMT) Is Strongly Expressed in a Subpopulation of Pinealocytes in the Male Rat Pineal Gland.

    PubMed

    Rath, Martin F; Coon, Steven L; Amaral, Fernanda G; Weller, Joan L; Møller, Morten; Klein, David C

    2016-05-01

    The rat pineal gland has been extensively used in studies of melatonin synthesis. However, the cellular localization of melatonin synthesis in this species has not been investigated. Here we focus on the localization of melatonin synthesis using immunohistochemical methods to detect the last enzyme in melatonin synthesis, acetylserotonin O-methyltransferase (ASMT), and in situ hybridization techniques to study transcripts encoding ASMT and two other enzymes in melatonin synthesis, tryptophan hydroxylase (TPH)-1 and aralkylamine N-acetyltransferase. In sections of the rat pineal gland, marked cell-to-cell differences were found in ASMT immunostaining intensity and in the abundance of Tph1, Aanat, and Asmt transcripts. ASMT immunoreactivity was localized to the cytoplasm in pinealocytes in the parenchyma of the superficial pineal gland, and immunopositive pinealocytes were also detected in the pineal stalk and in the deep pineal gland. ASMT was found to inconsistently colocalize with S-antigen, a widely used pinealocyte marker; this colocalization was seen in cells throughout the pineal complex and also in displaced pinealocyte-like cells of the medial habenular nucleus. Inconsistent colocalization between ASMT and TPH protein was also detected in the pineal gland. ASMT protein was not detected in extraepithalamic parts of the central nervous system or in peripheral tissues. The findings in this report are of special interest because they provide reason to suspect that melatonin synthesis varies significantly among individual pinealocytes.

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

    PubMed

    Takemura, Akihiro; Ueda, Satomi; Hiyakawa, Nanae; Nikaido, Yoshiaki

    2006-04-01

    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.

  10. In the Heat of the Night: Thermo-TRPV Channels in the Salmonid Pineal Photoreceptors and Modulation of Melatonin Secretion.

    PubMed

    Nisembaum, Laura Gabriela; Besseau, Laurence; Paulin, Charles-Hubert; Charpantier, Alice; Martin, Patrick; Magnanou, Elodie; Fuentès, Michael; Delgado, Maria-Jesus; Falcón, Jack

    2015-12-01

    Photoperiod plays an essential role in the synchronization of metabolism, physiology, and behavior to the cyclic variations of the environment. In vertebrates, information is relayed by the pineal cells and translated into the nocturnal production of melatonin. The duration of this signal corresponds to the duration of the night. In fish, the pinealocytes are true photoreceptors in which the amplitude of the nocturnal surge is modulated by temperature in a species-dependent manner. Thus, the daily and annual variations in the amplitude and duration of the nocturnal melatonin signal provide information on daily and calendar time. Both light and temperature act on the activity of the penultimate enzyme in the melatonin biosynthesis pathway, the arylalkylamine N-acetyltransferase (serotonin → N-acetylserotonin). Although the mechanisms of the light/dark regulation of melatonin secretion are quite well understood, those of temperature remain unelucidated. More generally, the mechanisms of thermoreception are unknown in ectotherms. Here we provide the first evidence that two thermotransient receptor potential (TRP) channels, TRPV1 and TRPV4, are expressed in the pineal photoreceptor cells of a teleost fish, in which they modulate melatonin secretion in vitro. The effects are temperature dependent, at least for TRPV1. Our data support the idea that the pineal of fish is involved in thermoregulation and that the pineal photoreceptors are also thermoreceptors. In other nervous and nonnervous tissues, TRPV1 and TRPV4 display a ubiquitous but quantitatively variable distribution. These results are a fundamental step in the elucidation of the mechanisms of temperature transduction in fish. PMID:26389691

  11. CSF generation by pineal gland results in a robust melatonin circadian rhythm in the third ventricle as an unique light/dark signal.

    PubMed

    Tan, Dun-Xian; Manchester, Lucien C; Reiter, Russel J

    2016-01-01

    Pineal gland is an important organ for the regulation of the bio-clock in all vertebrate species. Its major secretory product is melatonin which is considered as the chemical expression of darkness due to its circadian peak exclusively at night. Pineal melatonin can be either released into the blood stream or directly enter into the CSF of the third ventricle via the pineal recess. We have hypothesized that rather than the peripheral circulatory melatonin circadian rhythm serving as the light/dark signal, it is the melatonin rhythm in CSF of the third ventricle that serves this purpose. This is due to the fact that melatonin circadian rhythm in the CSF is more robust in terms of its extremely high concentration and its precise on/off peaks. Thus, extrapineal-generated melatonin or diet-derived melatonin which enters blood would not interfere with the bio-clock function of vertebrates. In addition, based on the relationship of the pineal gland to the CSF and the vascular structure of this gland, we also hypothesize that pineal gland is an essential player for CSF production. We feel it participates in both the formation and reabsorption of CSF. The mechanisms associated with these processes are reviewed and discussed in this brief review.

  12. Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland.

    PubMed

    Maronde, Erik; Saade, Anastasia; Ackermann, Katrin; Goubran-Botros, Hany; Pagan, Cecile; Bux, Roman; Bourgeron, Thomas; Dehghani, Faramarz; Stehle, Jörg H

    2011-08-01

    Time of day is communicated to the body through rhythmic cues, including pineal gland melatonin synthesis, which is restricted to nighttime. Whereas in most rodents transcriptional regulation of the arylalkylamine N-acetyltransferase (Aanat) gene is essential for rhythmic melatonin synthesis, investigations into nonrodent mammalian species have shown post-transcriptional regulation to be of central importance, with molecular mechanisms still elusive. Therefore, human pineal tissues, taken from routine autopsies were allocated to four time-of-death groups (night/dawn/day/dusk) and analyzed for daytime-dependent changes in phosphorylated AANAT (p31T-AANAT) and in acetyl-serotonin-methyltransferase (ASMT) expression and activity. Protein content, intracellular localization, and colocalization of p31T-AANAT and ASMT were assessed, using immunoblotting, immunofluorescence, and immunoprecipitation techniques. Fresh sheep pineal gland preparations were used for comparative purposes. The amount of p31T-AANAT and ASMT proteins as well as their intracellular localization showed no diurnal variation in autoptic human and fresh sheep pineal glands. Moreover, in human and sheep pineal extracts, AANAT could not be dephosphorylated, which was at variance to data derived from rat pineal extracts. P31T-AANAT and ASMT were often found to colocalize in cellular rod-like structures that were also partly immunoreactive for the pinealocyte process-specific marker S-antigen (arrestin) in both, human and sheep pinealocytes. Protein-protein interaction studies with p31T-AANAT, ASMT, and S-antigen demonstrated a direct association and formation of robust complexes, involving also 14-3-3. This work provides evidence for a regulation principle for AANAT activity in the human pineal gland, which may not be based on a p31T-AANAT phosphorylation/dephosphorylation switch, as described for other mammalian species.

  13. Tetrodotoxin administration in the suprachiasmatic nucleus prevents NMDA-induced reductions in pineal melatonin without influencing Per1 and Per2 mRNA levels.

    PubMed

    Paul, Ketema N; Gamble, Karen L; Fukuhara, Chiaki; Novak, Colleen M; Tosini, Gianluca; Albers, H Elliott

    2004-05-01

    The suprachiasmatic nucleus (SCN) of the anterior hypothalamus contains a light-entrainable circadian pacemaker. Neurons in the SCN are part of a circuit that conveys light information from retinal efferents to the pineal gland. Light presented during the night acutely increases mRNA levels of the circadian clock genes Per1 and Per2 in the SCN, and acutely suppresses melatonin levels in the pineal gland. The present study investigated whether the ability of light to increase Per1 and Per2 mRNA levels and suppress pineal melatonin levels requires sodium-dependent action potentials in the SCN. Per1 and Per2 mRNA levels in the SCN and pineal melatonin levels were measured in Syrian hamsters injected with tetrodotoxin (TTX) prior to light exposure or injection of N-methyl-D-aspartate (NMDA). TTX inhibited the ability of light to increase Per1 and Per2 mRNA levels and suppress pineal melatonin levels. TTX did not, however, influence the ability of NMDA to increase Per1 and Per2 mRNA levels, though it did inhibit the ability of NMDA to suppress pineal melatonin levels. These results demonstrate that action potentials in the SCN are not necessary for NMDA receptor activation to increase Per1 and Per2 mRNA levels, but are necessary for NMDA receptor activation to decrease pineal melatonin levels. Taken together, these data support the hypothesis that the mechanism through which light information is conveyed to the pacemaker in the SCN is separate from and independent of the mechanism through which light information is conveyed to the SCN cells whose efferents suppress pineal melatonin levels.

  14. Melatonin modulates intercellular communication among cultured chick astrocytes.

    PubMed

    Peters, Jennifer L; Cassone, Vincent M; Zoran, Mark J

    2005-01-01

    Melatonin, a pineal neurohormone, mediates circadian and seasonal processes in birds and mammals. Diencephalic astrocytes are sites of action, at least in birds, since they express melatonin receptors and melatonin affects their metabolism. We tested whether astrocytic calcium waves are also modulated by melatonin. Calcium waves, which we found to be regulated in cultured chick glial cells by an IP(3)-dependent mechanism, were potentiated by physiological concentrations of melatonin. Melatonin also increased resting calcium levels and reduced gap junctional coupling among astrocytes, at concentrations that facilitated calcium waves. These modulatory effects were diminished by melatonin receptor blockade and pertussis toxin (PTX). Thus, melatonin induced a functional shift in the mode of intercellular communication, between junctional coupling and calcium waves, among glial cells. We suggest a mechanism where neuroglial physiology, involving GTP-binding protein signaling pathways, links rhythmic circadian outputs to pervasive neurobehavioral states. PMID:15621008

  15. Melatonin and male reproduction.

    PubMed

    Li, Chunjin; Zhou, Xu

    2015-06-15

    Melatonin is a neurohormone secreted by the pineal gland whose concentrations in the body are regulated by both the dark-light and seasonal cycles. The reproductive function of seasonal breeding animals is clearly influenced by the circadian variation in melatonin levels. Moreover, a growing body of evidence indicates that melatonin has important effects in the reproduction of some non-seasonal breeding animals. In males, melatonin affects reproductive regulation in three main ways. First, it regulates the secretion of two key neurohormones, GnRH and LH. Second, it regulates testosterone synthesis and testicular maturation. Third, as a potent free radical scavenger that is both lipophilic and hydrophilic, it prevents testicular damage caused by environmental toxins or inflammation. This review summarizes the existing data on the possible biological roles of melatonin in male reproduction. Overall, the literature data indicate that melatonin affects the secretion of both gonadotropins and testosterone while also improving sperm quality. This implies that it has important effects on the regulation of testicular development and male reproduction.

  16. Ultradian oscillation in expression of four melatonin receptor subtype genes in the pineal gland of the grass puffer, a semilunar-synchronized spawner, under constant darkness.

    PubMed

    Ikegami, Taro; Maruyama, Yusuke; Doi, Hiroyuki; Hattori, Atsuhiko; Ando, Hironori

    2015-01-01

    Melatonin receptor gene expression as well as melatonin synthesis and secretion activities were examined in the pineal gland of the grass puffer, which exhibits unique lunar/tidal cycle-synchronized mass spawing: spawning occurs before high tide on the day of spring tide during spawing season. Melatonin synthesizing activity was assessed by the abundance of arylalkylamine N-acetyltransferase 2 (AANAT2) mRNA. The amount of aanat2 mRNA was low during light phase and initiated to increase after the light was turned off. The secretion of melatonin from primary pineal organ culture was stimulated after the light was turned off and ceased immediately after the light was turned on. The expression levels of four melatonin receptor subtype genes (mel 1a 1.4, mel 1a 1.7, mel1b, and mel1c) showed synchronous variations, and the levels tended to be high during the dark phase under light/dark conditions. These results suggest that the action of melatonin on the pineal gland is highly dependent on light and photoperiod, possibly with stronger action during night time. Under constant darkness, the expression of four melatonin receptor subtype genes showed unique ultradian oscillations with the period of 14.0-15.4 h, suggesting the presence of a circatidal oscillator in the pineal gland. The present results indicate that melatonin may serve local chronobiological functions in the pineal gland. These cyclic expressions of melatonin receptor genes in the pineal gland may be important in the control of the lunar/tidal cycle-synchronized mass spawning in the grass puffer.

  17. Ultradian oscillation in expression of four melatonin receptor subtype genes in the pineal gland of the grass puffer, a semilunar-synchronized spawner, under constant darkness

    PubMed Central

    Ikegami, Taro; Maruyama, Yusuke; Doi, Hiroyuki; Hattori, Atsuhiko; Ando, Hironori

    2015-01-01

    Melatonin receptor gene expression as well as melatonin synthesis and secretion activities were examined in the pineal gland of the grass puffer, which exhibits unique lunar/tidal cycle-synchronized mass spawing: spawning occurs before high tide on the day of spring tide during spawing season. Melatonin synthesizing activity was assessed by the abundance of arylalkylamine N-acetyltransferase 2 (AANAT2) mRNA. The amount of aanat2 mRNA was low during light phase and initiated to increase after the light was turned off. The secretion of melatonin from primary pineal organ culture was stimulated after the light was turned off and ceased immediately after the light was turned on. The expression levels of four melatonin receptor subtype genes (mel1a1.4, mel1a1.7, mel1b, and mel1c) showed synchronous variations, and the levels tended to be high during the dark phase under light/dark conditions. These results suggest that the action of melatonin on the pineal gland is highly dependent on light and photoperiod, possibly with stronger action during night time. Under constant darkness, the expression of four melatonin receptor subtype genes showed unique ultradian oscillations with the period of 14.0–15.4 h, suggesting the presence of a circatidal oscillator in the pineal gland. The present results indicate that melatonin may serve local chronobiological functions in the pineal gland. These cyclic expressions of melatonin receptor genes in the pineal gland may be important in the control of the lunar/tidal cycle-synchronized mass spawning in the grass puffer. PMID:25688184

  18. Alpha-2 adrenergic activity of bromocriptine and quinpirole in chicken pineal gland. Effects on melatonin synthesis and ( sup 3 H)rauwolscine binding

    SciTech Connect

    Zawilska, J.; Iuvone, P.M. )

    1990-12-01

    In the pineal gland and retina of chickens, serotonin N-acetyl-transferase (NAT) activity and melatonin content are modulated by different receptors, alpha-2 adrenergic receptors in pineal gland and D2-dopamine receptors in retina. The effect of two D2-dopamine receptor agonists, bromocriptine and quinpirole (LY 171555), on melatonin synthesis in these tissues was investigated. Systemic administrations of bromocriptine and quinpirole decreased nocturnal NAT activity and melatonin content of both pineal gland and retina. Bromocriptine was equipotent in the two tissues, whereas quinpirole was approximately 100-fold more potent in retina than in pineal gland. In pineal gland, the suppressive effects of bromocriptine and quinpirole on NAT activity were blocked by yohimbine, a selective alpha-2 adrenergic receptor antagonist, but not by spiperone, a D2-dopamine receptor antagonist. In contrast, bromocriptine- and quinpirole-induced decreases of the enzyme activity in retina were antagonized by spiperone, and not affected by yohimbine. The nocturnal increase of NAT activity of pineal glands in vitro was inhibited with an order of potency clonidine greater than bromocriptine greater than quinpirole. Additionally, bromocriptine and quinpirole displaced the specific binding of (3H)rauwolscine, an alpha-2 adrenergic receptor antagonist, to membranes from chicken pineal gland, with potencies comparable to those observed for inhibition of NAT activity in vitro. It is suggested that bromocriptine and quinpirole, in addition to their D2-dopaminergic activity, can stimulate alpha-2 adrenergic receptors in pineal gland of chicken.

  19. Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth

    SciTech Connect

    Reiter, R.J.; Anderson, L.E.; Buschbom, R.L.; Wilson, B.W.

    1988-01-01

    Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats. The findings are generally consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations.

  20. Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth

    SciTech Connect

    Reiter, R.J.; Anderson, L.E.; Buschbom, R.I.; Wilson, B.W.

    1988-02-01

    Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats and the findings are generally consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations. 15 refs., 1 fig., 1 tab.

  1. Diurnal expression of clock genes in pineal gland and brain and plasma levels of melatonin and cortisol in Atlantic salmon parr and smolts.

    PubMed

    Huang, Tien-sheng; Ruoff, Peter; Fjelldal, Per G

    2010-10-01

    In Atlantic salmon, the preadaptation to a marine life, i.e., parr-smolt transformation, and melatonin production in the pineal gland are regulated by the photoperiod. However, the clock genes have never been studied in the pineal gland of this species. The aim of the present study was to describe the diurnal expression of clock genes (Per1-like, Cry2, and Clock) in the pineal gland and brain of Atlantic salmon parr and smolts in freshwater, as well as plasma levels of melatonin and cortisol. By employing an out-of-season smolt production model, the parr-smolt transformation was induced by subjecting triplicate groups of parr to 6 wks (wks 0 to 6) under a 12 h:12 h light-dark (LD) regime followed by 6 wks (wks 6 to 12) of continuous light (LL). The measured clock genes in both pineal gland and brain and the plasma levels of melatonin and cortisol showed significant daily variations in parr under LD in wk 6, whereas these rhythms were abolished in smolts under LL in wk 12. In parr, the pineal Per1-like and Cry2 expression peaked in the dark phase, whereas the pineal Clock expression was elevated during the light phase. Although this study presents novel findings on the clock gene system in the teleost pineal gland, the role of this system in the regulation of smoltification needs to be studied in more detail.

  2. Comparative study of pineal clock gene and AANAT2 expression in relation to melatonin synthesis in Atlantic salmon (Salmo salar) and European seabass (Dicentrarchus labrax).

    PubMed

    McStay, Elsbeth; Migaud, Herve; Vera, Luisa Maria; Sánchez-Vázquez, Francisco Javier; Davie, Andrew

    2014-03-01

    The photoreceptive teleost pineal is considered to be essential to the generation, synchronisation and maintenance of biological rhythms, primarily via melatonin release. The role of internal (circadian clock) and external (light) signals controlling melatonin production in the fish pineal differs between species, yet the reasons underpinning this remain largely unknown. Whilst in salmonids, pineal melatonin is apparently regulated directly by light, in all other studied teleosts, rhythmic melatonin production persists endogenously under the regulation of clock gene expression. To better understand the role of clocks in teleost pineals, this study aimed to characterise the expression of selected clock genes in vitro under different photoperiodic conditions in comparison to in vivo in both Atlantic salmon (Salmo salar) and in European seabass (Dicentrarchus labrax) (in vitro 12L:12D), a species known to display endogenous rhythmic melatonin synthesis. Results revealed no rhythmic clock gene (Clock, Period 1 &2) expression in Atlantic salmon or European seabass (Clock and Period 1) pineal in vitro. However rhythmic expression of Cryptochrome 2 and Period 1 in the Atlantic salmon pineal was observed in vivo, which infers extra-pineal regulation of clocks in this species. No rhythmic arylalkylamine N-acetyltransferase 2 (Aanat2) expression was observed in the Atlantic salmon yet in the European seabass, circadian Aanat2 expression was observed. Subsequent in silico analysis of available Aanat2 genomic sequences reveals that Atlantic salmon Aanat2 promoter sequences do not contain similar regulatory architecture as present in European seabass, and previously described in other teleosts which alludes to a loss in functional connection in the pathway.

  3. Circadian regulation of pineal gland rhythmicity.

    PubMed

    Borjigin, Jimo; Zhang, L Samantha; Calinescu, Anda-Alexandra

    2012-02-01

    The pineal gland is a neuroendocrine organ of the brain. Its main task is to synthesize and secrete melatonin, a nocturnal hormone with diverse physiological functions. This review will focus on the central and pineal mechanisms in generation of mammalian pineal rhythmicity including melatonin production. In particular, this review covers the following topics: (1) local control of serotonin and melatonin rhythms; (2) neurotransmitters involved in central control of melatonin; (3) plasticity of the neural circuit controlling melatonin production; (4) role of clock genes in melatonin formation; (5) phase control of pineal rhythmicity; (6) impact of light at night on pineal rhythms; and (7) physiological function of the pineal rhythmicity.

  4. Modulation of pineal melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through NF-κB activation.

    PubMed

    Villela, Darine; Atherino, Victoria Fairbanks; Lima, Larissa de Sá; Moutinho, Anderson Augusto; do Amaral, Fernanda Gaspar; Peres, Rafael; Martins de Lima, Thais; Torrão, Andréa da Silva; Cipolla-Neto, José; Scavone, Cristóforo; Afeche, Solange Castro

    2013-01-01

    The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF- κ B activation were analyzed in astrocytes and pinealocytes. TNF- α 's possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF- α . Moreover, the activation of the astrocytic NF- κ B seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF- κ B transcription factor and possibly by subsequent TNF- α release.

  5. Melatonin

    PubMed Central

    Pévet, Paul

    2002-01-01

    Melatonin (MEL) is a hormone synthesized and secreted by the pineal gland deep within the brain in response to photoperiodic cues relayed from the retina via an endogenous circadian oscillator within the suprachiasmatic nucleus in the hypothalamus. The circadian rhythm of melatonin production and release, characterized by nocturnal activity and daytime quiescence, is an important temporal signal to the body structures that can read it. Melatonin acts through high-affinity receptors located centrally and in numerous peripheral organs. Different receptor subtypes have been cloned and characterized: MT1 and MT2 (transmembrane G-protein-coupled receptors), and MT3. However, their physiological role remains unelucidated, although livestock management applications already include the control of seasonal breeding and milk production. As for potential therapeutic applications, exogenous melatonin or a melatonin agonist and selective 5-hydroxytrypiamine receptor (5-HT2c) antagonist, eg, S 20098, can be used to manipulate circadian processes such as the sleep-vake cycle, which are frequently disrupted in many conditions, most notably seasonal affective disorder. PMID:22034091

  6. Melatonin and Ischemic Stroke: Mechanistic Roles and Action

    PubMed Central

    Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

    2015-01-01

    Stroke is one of the most devastating neurological disabilities and brain's vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke. PMID:26435711

  7. Neurobiological effects of melatonin as related to cancer.

    PubMed

    Hoang, Ba X; Shaw, David G; Pham, Phuong T; Levine, Stephen A

    2007-12-01

    Melatonin is a neurohormone naturally found in humans. Melatonin plays a role in maintaining sleep-wake rhythms; supplementation may help to regulate sleep disturbance that occur with jet lag, rotating shift-work and depression. Preliminary study of melatonin has shown potential for use in the treatment of epilepsy, tinnitus, migraine and neurodegenerative diseases. The latest publication in the Journal of Pineal Research by Edward Mills and colleagues has shown a compelling role of melatonin for the treatment of cancer. Melatonin's consistent relationship with cancer has been shown in many studies assessing links between shift work and cancer rates. High levels of melatonin have been linked to slower cancer progression. How melatonin affects cancer remains largely unclear. Although previous studies suggest different possible mechanisms, many of them are far distant from the primary physiological role of melatonin as a neurohormone. Conflicting studies are found on the role of melatonin in neurodegenerative diseases and cancer. In this article, we try to build and substantiate a neurobiological concept for the anticancer effects of melatonin. PMID:18090123

  8. Effects of Melatonin on Morphological and Functional Parameters of the Pineal Gland and Organs of Immune System in Rats During Natural Light Cycle and Constant Illumination.

    PubMed

    Litvinenko, G I; Shurlygina, A V; Gritsyk, O B; Mel'nikova, E V; Tenditnik, M V; Avrorov, P A; Trufakin, V A

    2015-10-01

    We studied the response of the pineal gland and organs of the immune system to melatonin treatment in Wistar rats kept under conditions of abnormal illumination regimen. The animals were kept under natural light regimen or continuous illumination for 14 days and then received daily injections of melatonin (once a day in the evening) for 7 days. Administration of melatonin to rats kept at natural light cycle was followed by a decrease in percent ratio of CD4+8+ splenocytes and CD4-8+ thymocytes. In 24-h light with the following melatonin injections were accompanied by an increase in percent rate and absolute amount of CD4+8+ cells in the spleen, and a decrease in percent rate of CD11b/c and CD4-8+ splenocytes. In the thymus amount of CD4-8+ cells increased, and absolute number of CD4+25+ cells reduced. Melatonin significantly decreased lipofuscin concentration in the pineal gland during continuous light. Direction and intensity of effects of melatonin on parameters of cell immunity and state of the pineal gland were different under normal and continuous light conditions. It should be taken into account during using of this hormone for correction of immune and endocrine impairments developing during change in light/dark rhythm.

  9. Melatonin synthesis impairment as a new deleterious outcome of diabetes-derived hyperglycemia.

    PubMed

    Amaral, Fernanda G; Turati, Ariane O; Barone, Mark; Scialfa, Julieta H; do Carmo Buonfiglio, Daniella; Peres, Rafael; Peliciari-Garcia, Rodrigo A; Afeche, Solange C; Lima, Larissa; Scavone, Cristoforo; Bordin, Silvana; Reiter, Russel J; Menna-Barreto, Luiz; Cipolla-Neto, José

    2014-08-01

    Melatonin is a neurohormone that works as a nighttime signal for circadian integrity and health maintenance. It is crucial for energy metabolism regulation, and the diabetes effects on its synthesis are unresolved. Using diverse techniques that included pineal microdialysis and ultrahigh-performance liquid chromatography, the present data show a clear acute and sustained melatonin synthesis reduction in diabetic rats as a result of pineal metabolism impairment that is unrelated to cell death. Hyperglycemia is the main cause of several diabetic complications, and its consequences in terms of melatonin production were assessed. Here, we show that local high glucose (HG) concentration is acutely detrimental to pineal melatonin synthesis in rats both in vivo and in vitro. The clinically depressive action of high blood glucose concentration in melatonin levels was also observed in type 1 diabetes patients who presented a negative correlation between hyperglycemia and 6-sulfatoxymelatonin excretion. Additionally, high-mean-glycemia type 1 diabetes patients presented lower 6-sulfatoxymelatonin levels when compared to control subjects. Although further studies are needed to fully clarify the mechanisms, the present results provide evidence that high circulating glucose levels interfere with pineal melatonin production. Given the essential role played by melatonin as a powerful antioxidant and in the control of energy homeostasis, sleep and biological rhythms and knowing that optimal glycemic control is usually an issue for patients with diabetes, melatonin supplementation may be considered as an additional tool to the current treatment.

  10. The pineal complex and melatonin affect the expression of the daily rhythm of behavioral thermoregulation in the green iguana.

    PubMed

    Tosini, G; Menaker, M

    1996-01-01

    Daily variation in the body temperature of the green iguana (Iguana iguana) was studied by telemetry in laboratory photo-thermal enclosures under a 12Light:12Dark (L:D) photoperiod. The lizards showed robust daily rhythms of thermoregulation maintaining their body temperatures (Tb) at higher levels during the day than during the night. Some animals maintained rhythmicity when kept in constant darkness. On light:dark cycles parietalectomy produced only a transient increase of median Tb in the first or second night following the operation. Pinealectomized lizards on the other hand maintained their body temperatures as significantly lower levels during the day and at significantly higher levels during the night than did sham-operated or intact lizards. This effect was apparently permanent, since one month after pinealectomy lizards still displayed the altered pattern. Plasma melatonin levels in intact animals were high during the night and low during the day and were unaffected by parietalectomy. Pinealectomized lizards showed low levels of plasma melatonin during both the day and the night. A daily intraperitoneal injection of melatonin in pinealectomized animals given a few minutes after the light to dark transition decreased the body temperatures selected by the lizards during the night and increased the body temperatures selected during the following day. Control injections of saline solution had no effect. The significance of these results is discussed in relation to the role of the pineal complex and melatonin in the mediation of thermoregulatory behavior.

  11. Photic and circadian regulation of retinal melatonin in mammals

    NASA Technical Reports Server (NTRS)

    Tosini, G.; Fukuhara, C.

    2003-01-01

    Several studies have established that melatonin synthesis occurs in the retina of vertebrates, including mammals. In mammals, a subpopulation of photoreceptors (probably the cones) synthesize melatonin. Melatonin synthesis in the retina is elevated at night and reduced during the day in a fashion similar to events in the pineal gland. Both the MT1 and MT2 melatonin receptors are present in the retina and retinal melatonin does not contribute to circulating levels, suggesting that retinal melatonin acts locally as a neurohormone and/or neuromodulator. Melatonin synthesis in the retina of mammals is under the control of a circadian oscillator, and circadian rhythms in melatonin synthesis and/or release have been described for several species of mammals. These rhythms are present in vivo, persist in vitro, are entrained by light and are temperature compensated. The cloning of the gene responsible for the synthesis of the enzyme arylalkylamine N-acetyltransferase (the key enzyme in the melatonin biosynthetic pathway) has allowed studies of the molecular mechanisms responsible for the generation of retinal melatonin rhythmicity. The present review focuses on the cellular and molecular mechanisms that regulate melatonin synthesis. In particular, we discuss how the photic environment and the circadian clock interact in determining melatonin levels, in addition to the role that melatonin plays in retinal physiology.

  12. Antioxidant properties of melatonin--an emerging mystery.

    PubMed

    Beyer, C E; Steketee, J D; Saphier, D

    1998-11-15

    Over three centuries ago, the French philosopher René Descartes described the pineal gland as "the seat of the soul." However, it was not until the late 1950s that the chemical identity and biosynthesis of melatonin, the principal hormone secreted by the pineal body, were revealed. Melatonin, named from the Greek melanos, meaning black, and tonos, meaning color, is a biogenic amine with structural similarities to serotonin. The mechanisms mediating the synthesis of melatonin are transcriptionally regulated by the photoperiodic environment. Once synthesized, the neurohormone is a biologic modulator of mood, sleep, sexual behavior, reproductive alterations, immunologic function, and circadian rhythms. Moreover, melatonin exerts its regulatory roles through high-affinity, pertussis toxin-sensitive, G-protein (or guanine nucleotide binding protein) coupled receptors that reside primarily in the eye, kidney, gastrointestinal tract, blood vessels, and brain. Additional evidence also indicates a role for melatonin in aging and age-related diseases, probably related to its efficient free radical scavenger (or antioxidant) activity. The potential clinical benefit of melatonin as an antioxidant is remarkable, suggesting that it may be of use in the treatment of many pathophysiological disease states including various cancers, hypertension, pulmonary diseases, and a variety of neurodegenerative diseases such as Alzheimer's disease. This review summarizes the biosynthesis of melatonin and its many endocrine and physiological functions, including its therapeutic potential in human disease states. Emphasis is placed on the recent speculations indicating that this pineal hormone serves as an endogenous antioxidant agent with proficient free radical scavenging activity.

  13. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases.

    PubMed

    Stehle, Jörg H; Saade, Anastasia; Rawashdeh, Oliver; Ackermann, Katrin; Jilg, Antje; Sebestény, Tamás; Maronde, Erik

    2011-08-01

    The human pineal gland is a neuroendocrine transducer that forms an integral part of the brain. Through the nocturnally elevated synthesis and release of the neurohormone melatonin, the pineal gland encodes and disseminates information on circadian time, thus coupling the outside world to the biochemical and physiological internal demands of the body. Approaches to better understand molecular details behind the rhythmic signalling in the human pineal gland are limited but implicitly warranted, as human chronobiological dysfunctions are often associated with alterations in melatonin synthesis. Current knowledge on melatonin synthesis in the human pineal gland is based on minimally invasive analyses, and by the comparison of signalling events between different vertebrate species, with emphasis put on data acquired in sheep and other primates. Together with investigations using autoptic pineal tissue, a remnant silhouette of premortem dynamics within the hormone's biosynthesis pathway can be constructed. The detected biochemical scenario behind the generation of dynamics in melatonin synthesis positions the human pineal gland surprisingly isolated. In this neuroendocrine brain structure, protein-protein interactions and nucleo-cytoplasmic protein shuttling indicate furthermore a novel twist in the molecular dynamics in the cells of this neuroendocrine brain structure. These findings have to be seen in the light that an impaired melatonin synthesis is observed in elderly and/or demented patients, in individuals affected by Alzheimer's disease, Smith-Magenis syndrome, autism spectrum disorder and sleep phase disorders. Already, recent advances in understanding signalling dynamics in the human pineal gland have significantly helped to counteract chronobiological dysfunctions through a proper restoration of the nocturnal melatonin surge.

  14. Light-Emitting Diodes and Cool White Fluorescent Light Similarly Suppress Pineal Gland Melatonin and Maintain Retinal Function and Morphology in the Rat. Part 1

    NASA Technical Reports Server (NTRS)

    Holley, Daniel C.; Heeke, D.; Mele, G.

    1999-01-01

    Currently, the light sources most commonly used in animal habitat lighting are cool white fluorescent or incandescent lamps. We evaluated a novel light-emitting diode (LED) light source for use in animal habitat lighting by comparing its effectiveness to cool white fluorescent light (CWF) in suppressing pineal gland melatonin and maintaining normal retinal physiology and morphology in the rat. Results of pineal melatonin suppression experiments showed equal suppression of pineal melatonin concentrations for LED light and CWF light at five different light illuminances (100, 40, 10, 1 and 0.1 lux). There were no significant differences in melatonin suppression between LED and CWF light when compared to unexposed controls. Retinal physiology was evaluated using electroretinography. Results show no differences in a-wave implicit times and amplitudes or b-wave implicit times and amplitudes between 100-lux LED-exposed rats and 100-lux CWF-exposed rats. Results of retinal histology assessment show no differences in retinal thickness rod outer segment length and number of rod nuclei between rats exposed to 100-lux LED and 100-lux CWF for days. Furthermore, the retinal pigmented epithelium and rod outer segments of all eyes observed were in good condition and of normal thickness. This study indicates that LED light does not cause retinal damage and can suppress pineal melatonin at similar intensities as a conventional CWF light source. These data suggest that LED light sources may be suitable replacements for conventional light sources used in the lighting of rodent vivariums while providing many mechanical and economical advantages.

  15. Analysis of adrenergic regulation of melatonin synthesis in Siberian hamster pineal emphasizes the role of HIOMT.

    PubMed

    Ceinos, R M; Chansard, M; Revel, F; Calgari, C; Míguez, J M; Simonneaux, V

    2004-01-01

    Seasonal variations of environmental factors are translated into annual fluctuations in synthesis and release of melatonin, which in turn acts as a neuroendocrine messenger for the synchronization of annual functions. So far, most studies performed to understand the regulation of melatonin synthesis have used the non seasonal laboratory rat. It was demonstrated that nocturnal melatonin synthesis depends on alpha- and beta-adrenergic activation of the enzyme arylalkylamine N-acetyltransferase (AA-NAT). In this study, we investigated the mechanisms of melatonin synthesis in the Siberian hamster, a seasonal species with marked photoperiodic variation in melatonin peak duration and amplitude. A beta-adrenergic receptor agonist alone markedly stimulated AA-NAT activity and melatonin synthesis and release. An alpha-adrenergic receptor agonist, while having no effect per se, potentiated the beta-adrenergic stimulation of AA-NAT activity both in vitro and in vivo. Strikingly, the potentiation of AA-NAT activity did not result in a potentiation of melatonin synthesis, suggesting that the rate of melatonin production is limited downstream in the metabolic pathway, most probably at the level of hydroxyindole-O-methyltransferase (HIOMT). HIOMT presented a constitutively high activity that was not acutely (within hours) stimulated by beta-adrenergic agonist, but was rather up-regulated by chronic application of the agonist. This long-term beta-adrenergic regulation may explain the reported large photoperiodic variation of HIOMT activity that drives the photoperiodic variation in melatonin peak.

  16. Neural regulation of dark-induced abundance of arylalkylamine N-acetyltransferase (AANAT) and melatonin in the carp (Catla catla) pineal: an in vitro study.

    PubMed

    Seth, Mohua; Maitra, Saumen Kumar

    2011-08-01

    In all the vertebrates, synthesis of melatonin and its rhythm-generating enzyme arylalkylamine N-acetyltransferase (AANAT) reaches its peak in the pineal during the night in a daily light-dark cycle, but the role of different neuronal signals in their regulation were unknown for any fish. Hence, the authors used specific agonist and antagonists of receptors for different neuronal signals and regulators of intracellular calcium (Ca(2+)) and adenosine 3',5'-cyclic monophosphate (cAMP) in vitro to study their effects on the abundance of AANAT and titer of melatonin in the carp (Catla catla) pineal. Western blot analysis followed by quantitative analysis of respective immunoblot data for AANAT protein, radioimmunoassay of melatonin, and spectrophotometric analysis of Ca(2+) in the pineal revealed stimulatory effects of both adrenergic (α(1) and β(1)) and dopaminergic (D(1)) agonists and cholinergic (both nicotinic and muscarinic) antagonists, inhibition by both adrenergic and dopaminergic antagonists and cholinergic agonists, but independent of the influence of any agonists or antagonists of α(2)-adrenergic receptors. Band intensity of AANAT and concentration of melatonin in the pineal were also enhanced by the intracellular calcium-releasing agent, activators of both calcium channel and adenylate cyclase, and phophodiesterase inhibitor, but suppressed by inhibitor of calcium channel and adenylate cyclase as well as activator of phophodiesterase. Moreover, an inhibitory effect of light on the pineal AANAT and melatonin was blocked by both cAMP and proteasomal proteolysis inhibitor MG132. Collectively, these data suggest that dark-induced abundance of AANAT and melatonin synthesis in the carp pineal are a multineuronal function, in which both adrenergic (α(1) and β(1), but not α(2)) and dopaminergic signals are stimulatory, whereas cholinergic signals are inhibitory. This study also provides indications, though arguably not conclusive evidence, that in either case

  17. Twenty-four-hour patterns of pineal melatonin and pituitary and plasma prolactin in male rats under 'natural' and artificial lighting conditions.

    PubMed

    Laakso, M L; Porkka-Heiskanen, T; Alila, A; Peder, M; Johansson, G

    1988-09-01

    Natural lighting differs from usual artificial lighting mainly as follows: it has larger spectral composition, fluctuations of intensity during the day, higher intensity levels during the night (moonlight, starlight), and gradual changes of illuminance at dawn and dusk. The present experiment was performed in order to study whether these features of lighting affect the 24-hour patterns of melatonin and prolactin in male rats. The rats were kept 7 days in 'natural' lighting (sunlight through windows) or in artificial lighting (cool white fluorescent lamps) of similar periodicities (13/11 h light/dark). The samples were collected at 3-hour intervals during a 24-hour period. Pineal melatonin contents, pituitary prolactin contents, and plasma prolactin concentrations were measured radioimmunologically. The nocturnal pineal melatonin contents were higher and the daytime contents lower in natural than in artificial lighting conditions. A corresponding 'strengthening of rhythm' of prolactin was found in natural lighting. A reason for the higher amplitude variation of melatonin in the natural lighting conditions may be the gradual changes of illuminance at dawn and dusk. The different pituitary and plasma prolactin patterns of the rats kept in the two lighting conditions might partly be explained by a stimulatory effect of melatonin on the production and secretion of prolactin, but other regulatory factors had to be involved, too.

  18. Diurnal Profiles of Melatonin Synthesis-Related Indoles, Catecholamines and Their Metabolites in the Duck Pineal Organ

    PubMed Central

    Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

    2014-01-01

    This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime. PMID:25032843

  19. Diurnal profiles of melatonin synthesis-related indoles, catecholamines and their metabolites in the duck pineal organ.

    PubMed

    Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

    2014-07-16

    This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime.

  20. Photoreceptor proteins and melatonin rhythm generating AANAT in the carp pineal: Temporal organization and correlation with natural photo-thermal cues.

    PubMed

    Seth, Mohua; Maitra, Saumen Kumar

    2010-04-01

    We studied temporal organization of both the photoreceptor (rod-like opsin, alpha subunit of the G protein transducin or alpha-TD) and melatonin generating (AANAT) proteins in the same pineal of a tropical surface dwelling free-living carp Catla catla, and analyzed possible correlation between them as well as with natural photo-thermal variables in an annual cycle. The pineal from individual fish was collected at four different time points (06.00 h, 12.00 h, 18.00 h, and 24.00 h) in a 24.00 h cycle and the same was repeated in four distinct seasons in an annual reproductive cycle to study each protein following Western blot and densitometric analyses of respective immunoblots. The rod-like opsin was represented by four distinct bands, a closely spaced doublet of 39 kDa and bands of 78 and 115 kDa. Two separate bands, one at 43 kDa and another at 65 kDa, were detected for alpha-TD, and a single band at 23 kDa for AANAT. Both the pineal photoreceptor proteins exhibited an identical pattern of diurnal variations with a peak at midday (12.00 h) and fall at midnight (24.00 h), while maximum band intensity of AANAT was noted in midnight (24.00 h) and minimum at midday (12.00 h) depicting a significant negative correlation (p<0.001) between them. Likewise, in an annual cycle, a significant (p<0.01) negative correlation was found between the expression of each pineal photoreceptor protein (being highest during the spawning phase) and AANAT (maximum during the post-spawning phase). Seasonal fluctuations of both the photoperiod and water temperature exhibited a significant (p<0.01) positive correlation with the expression of pineal photoreceptor proteins and a significant (p<0.05) negative correlation with the pineal AANAT. Collectively, the present phenological study is the first report on temporal organization of pineal photoreceptor proteins and their correlation with the melatonin rhythm-generating enzyme AANAT as well as environmental photo-thermal cues depicting their

  1. Influence of moonlight on mRNA expression patterns of melatonin receptor subtypes in the pineal organ of a tropical fish.

    PubMed

    Park, Yong-Ju; Park, Ji-Gweon; Takeuchi, Yuki; Hur, Sung-Pyo; Lee, Young-Don; Kim, Se-Jae; Takemura, Akihiro

    2014-04-01

    The goldlined spinefoot, Siganus guttatus, is a lunar-synchronized spawner, which repeatedly releases gametes around the first quarter moon during the reproductive season. A previous study reported that manipulating moonlight brightness at night disrupted synchronized spawning, suggesting involvement of this natural light source in lunar synchronization. The present study examined whether the mRNA expression pattern of melatonin receptor subtypes MT1 and Mel1c in the pineal organ of the goldlined spinefoot is related to moonlight. Real-time quantitative polymerase chain reaction analysis revealed that the abundance of MT1 and Mel1c mRNA at midnight increased during the new moon phase and decreased during the full moon phase. Exposing fish to moonlight intensity during the full moon period resulted in a decrease in Mel1c mRNA abundance within 1h. Fluctuations in the melatonin receptor genes according to changes in the moon phase agreed with those of melatonin levels in the blood. These results indicate that periodic changes in cues from the moon influence melatonin receptor mRNA expression levels. The melatonin-melatonin receptor system may play a role in predicting the moon phase through changes in night brightness. PMID:24269345

  2. Influence of moonlight on mRNA expression patterns of melatonin receptor subtypes in the pineal organ of a tropical fish.

    PubMed

    Park, Yong-Ju; Park, Ji-Gweon; Takeuchi, Yuki; Hur, Sung-Pyo; Lee, Young-Don; Kim, Se-Jae; Takemura, Akihiro

    2014-04-01

    The goldlined spinefoot, Siganus guttatus, is a lunar-synchronized spawner, which repeatedly releases gametes around the first quarter moon during the reproductive season. A previous study reported that manipulating moonlight brightness at night disrupted synchronized spawning, suggesting involvement of this natural light source in lunar synchronization. The present study examined whether the mRNA expression pattern of melatonin receptor subtypes MT1 and Mel1c in the pineal organ of the goldlined spinefoot is related to moonlight. Real-time quantitative polymerase chain reaction analysis revealed that the abundance of MT1 and Mel1c mRNA at midnight increased during the new moon phase and decreased during the full moon phase. Exposing fish to moonlight intensity during the full moon period resulted in a decrease in Mel1c mRNA abundance within 1h. Fluctuations in the melatonin receptor genes according to changes in the moon phase agreed with those of melatonin levels in the blood. These results indicate that periodic changes in cues from the moon influence melatonin receptor mRNA expression levels. The melatonin-melatonin receptor system may play a role in predicting the moon phase through changes in night brightness.

  3. Pertussis toxin-sensitive G-protein mediates the alpha 2-adrenergic receptor inhibition of melatonin release in photoreceptive chick pineal cell cultures

    SciTech Connect

    Pratt, B.L.; Takahashi, J.S.

    1988-07-01

    The avian pineal gland is a photoreceptive organ that has been shown to contain postjunctional alpha 2-adrenoceptors that inhibit melatonin synthesis and/or release upon receptor activation. Physiological response and (32P)ADP ribosylation experiments were performed to investigate whether pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) were involved in the transduction of the alpha 2-adrenergic signal. For physiological response studies, the effects of pertussis toxin on melatonin release in dissociated cell cultures exposed to norepinephrine were assessed. Pertussis toxin blocked alpha 2-adrenergic receptor-mediated inhibition in a dose-dependent manner. Pertussis toxin-induced blockade appeared to be noncompetitive. One and 10 ng/ml doses of pertussis toxin partially blocked and a 100 ng/ml dose completely blocked norepinephrine-induced inhibition. Pertussis toxin-catalyzed (32P)ADP ribosylation of G-proteins in chick pineal cell membranes was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Membranes were prepared from cells that had been pretreated with 0, 1, 10, or 100 ng/ml pertussis toxin. In the absence of pertussis toxin pretreatment, two major proteins of 40K and 41K mol wt (Mr) were labeled by (32P)NAD. Pertussis toxin pretreatment of pineal cells abolished (32P) radiolabeling of the 40K Mr G-protein in a dose-dependent manner. The norepinephrine-induced inhibition of both cAMP efflux and melatonin release, as assessed by RIA of medium samples collected before membrane preparation, was also blocked in a dose-dependent manner by pertussis toxin. Collectively, these results suggest that a pertussis toxin-sensitive 40K Mr G-protein labeled by (32P)NAD may be functionally associated with alpha 2-adrenergic signal transduction in chick pineal cells.

  4. Melatonin-synthesizing enzymes in pineal, retina, liver, and gut of the goldfish (Carassius): mRNA expression pattern and regulation of daily rhythms by lighting conditions.

    PubMed

    Velarde, Elena; Cerdá-Reverter, Jose Miguel; Alonso-Gómez, Angel Luis; Sánchez, Elisa; Isorna, Esther; Delgado, María Jesús

    2010-07-01

    It has been suggested that melatonin is synthesized in nonphotosensitive organs of vertebrates in addition to the well-known sites of the pineal gland and retina. However, very few studies have demonstrated the gene expression of melatonin-synthesizing enzymes in extrapineal and extraretinal locations. This study focuses on the circadian expression of the two key enzymes of the melatoninergic pathway, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), in central and peripheral locations of a teleost fish, the goldfish (Carassius auratus). First, the full-length cDNA sequences corresponding to the goldfish AANAT-2 (gAanat-2) and HIOMT-2 (gHiomt-2) were cloned, showing high similarity with other teleost sequences. Two forms of AANAT exist in teleosts. Here, for the first time, two isoforms of HIOMT are deduced from phylogenetic analysis. Moreover, both HIOMT and AANAT were detected in several peripheral locations, including liver and gut, the present results being the first to find HIOMT in nonphotosensitive structures of a fish species. Second, quantitative real-time polymerase chain reaction (PCR) studies were performed to investigate regulation of gAanat-2 in pineal and peripheral locations of goldfish maintained under different lighting conditions. The current results show circadian rhythms in Aanat-2 and Hiomt-2 transcripts in liver and hindgut, suggesting a local melatonin synthesis in goldfish. Moreover, the analysis of daily expression of gAanat-2 under different lighting conditions, including continuous light (24L) and darkness (24D) revealed light-dependent rhythms in the pineal and retina, as expected, but also in liver and hindgut. The persistence in hindgut of these gAanat-2 rhythms under both constant conditions, 24L and 24D, suggests expression of this transcript is governed by a circadian clock and entrained by nonphotic cues. Finally, the current results support the existence of melatonin synthesis in gut and

  5. Influence of photoperiod on pineal melatonin synthesis, fur color, body weight, and reproductive function in the female Djungarian hamster, Phodopus sungorus.

    PubMed

    Lerchl, A; Schlatt, S

    1993-01-01

    In order to investigate female Djungarian hamsters' reactions to changes of the photoperiod, the following two experiments were performed. Experiment I: Age-matched female hamsters were exposed to either short (8L:16D) or long days (16L:8D) for 38 weeks. Initially, the short-day group showed a decline in body weight, associated with changes in gonadal function and fur color. This was not maintained by the short-day group which returned, on the most part, to long-day levels, thus becoming insensitive to this regressive lighting regimen. The time courses of these events compare well with those observed in males, which suggests a common mechanism. Experiment II: Two groups of female hamsters were exposed for 8 weeks to either long days or short days. At the end of the test period, the diurnal variations in pineal content of melatonin, serotonin, hydroxyindole acetic acid, and serum melatonin were estimated, revealing marked differences between the two groups. Not only was there a prolongation of melatonin synthesis observed in the short-day animals, but there was also a significant elevation of the melatonin levels when compared to the long-day animals. Together with recent findings in males, these findings lend support to the hypothesis that, in the Djungarian hamster, the elevation of nocturnal melatonin levels may be of additional significance, with respect to the physiological changes induced by short-day photoperiods. PMID:7685505

  6. Adrenergic activation of melatonin secretion in ovine pineal explants in short-term superfusion culture occurs via protein synthesis independent and dependent phenomena.

    PubMed

    Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

    2014-01-01

    The ovine pineal is generally considered as an interesting model for the study on adrenergic regulation of melatonin secretion due to some functional similarities with this gland in the human. The present investigations, performed in the superfusion culture of pineal explants, demonstrated that the norepinephrine-induced elevation of melatonin secretion in ovine pinealocytes comprised of two subsequent periods: a rapid increase phase and a slow increase phase. The first one included the quick rise in release of N-acetylserotonin and melatonin, occurring parallel to elevation of NE concentration in the medium surrounding explants. This rapid increase phase was not affected by inhibition of translation. The second, slow increase phase began after NE level had reached the maximum concentration in the culture medium and lasted about two hours. It was completely abolished by the treatment with translation inhibitors. The obtained results showed for the first time that the regulation of N-acetylserotonin synthesis in pinealocytes of some species like the sheep involves the on/off mechanism, which is completely independent of protein synthesis and works very fast. They provided strong evidence pointing to the need of revision of the current opinion that arylalkylamines N-acetyltransferase activity in pinealocytes is controlled exclusively by changes in enzyme abundance.

  7. Adrenergic Activation of Melatonin Secretion in Ovine Pineal Explants in Short-Term Superfusion Culture Occurs via Protein Synthesis Independent and Dependent Phenomena

    PubMed Central

    2014-01-01

    The ovine pineal is generally considered as an interesting model for the study on adrenergic regulation of melatonin secretion due to some functional similarities with this gland in the human. The present investigations, performed in the superfusion culture of pineal explants, demonstrated that the norepinephrine-induced elevation of melatonin secretion in ovine pinealocytes comprised of two subsequent periods: a rapid increase phase and a slow increase phase. The first one included the quick rise in release of N-acetylserotonin and melatonin, occurring parallel to elevation of NE concentration in the medium surrounding explants. This rapid increase phase was not affected by inhibition of translation. The second, slow increase phase began after NE level had reached the maximum concentration in the culture medium and lasted about two hours. It was completely abolished by the treatment with translation inhibitors. The obtained results showed for the first time that the regulation of N-acetylserotonin synthesis in pinealocytes of some species like the sheep involves the on/off mechanism, which is completely independent of protein synthesis and works very fast. They provided strong evidence pointing to the need of revision of the current opinion that arylalkylamines N-acetyltransferase activity in pinealocytes is controlled exclusively by changes in enzyme abundance. PMID:25133175

  8. The foetal pig pineal gland is richly innervated by nerve fibres containing catecholamine-synthesizing enzymes, neuropeptide Y (NPY) and C-terminal flanking peptide of NPY, but it does not secrete melatonin.

    PubMed

    Bulc, Michał; Lewczuk, Bogdan; Prusik, Magdalena; Całka, Jarosław

    2013-05-01

    Innervation of the mammalian pineal gland during prenatal development is poorly recognized. Therefore, immunofluorescence studies of the pineals of 70- and 90-day-old foetuses of the domestic pig were performed using antibodies against tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DβH), neuropeptide Y (NPY) and C-terminal flanking peptide of NPY (CPON). The investigated glands were supplied by numerous nerve fibres containing TH and DβH. The density of these fibres was higher in the distal and middle parts of the gland than in the proximal one. NPY and CPON were identified in the majority of DβH-positive fibres as well as in a small population of DβH-negative fibres localized mainly in the proximal part of the pineal. The immunoreactive fibres were more numerous in 90-day-old foetuses than in 70-day-old ones. The effect of norepinephrine on melatonin secretion by the foetal pineals in the short-term organ culture was studied to determine the role of DβH-positive fibres during prenatal life. For the same purpose melatonin was measured in the blood in the umbilical cords and in the jugular vein of the mother. The pineals of both groups of foetuses did not secrete melatonin in the organ culture, independently of the presence or absence of norepinephrine in the medium. Melatonin concentrations in the blood in the umbilical cords of foetuses from the same litter and in the jugular vein of their mother were similar. The presence of adrenergic nerve fibres in the pig pineal during gestation does not seem to be associated with the control of melatonin secretion.

  9. The role of melatonin in anaesthesia and critical care.

    PubMed

    Kurdi, Madhuri S; Patel, Tushar

    2013-03-01

    Melatonin is a neurohormone secreted by the pineal gland. It is widely present in both plant and animal sources. In several countries, it is sold over the counter as tablets and as food supplement or additive. Currently, it is most often used to prevent jet lag and to induce sleep. It has been and is being used in several clinical trials with different therapeutic approaches. It has sedative, analgesic, anti-inflammatory, anti-oxidative and chronobiotic effects. In the present review, the potential therapeutic benefits of melatonin in anaesthesia and critical care are presented. This article aims to review the physiological properties of melatonin and how these could prove useful for several clinical applications in perioperative management, critical care and pain medicine. The topic was handsearched from textbooks and journals and electronically from PubMed, and Google scholar using text words.

  10. Is melatonin useful for jet lag?

    PubMed

    Tortorolo, Francisco; Farren, Florencia; Rada, Gabriel

    2015-12-21

    Jet lag syndrome is an exogenous circadian rhythm sleep disorder, frequently reported in travelers who cross multiple time zones in a short period of time. Oral melatonin -a pineal neurohormone normally produced during darkness and responsible for regulating the body's circadian rhythms- has been used as treatment for this condition. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including 11 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the use of oral melatonin probably reduces symptoms associated with jet lag syndrome. It is not clear whether its use produces adverse effects; however, these would be probably mild.

  11. Is melatonin useful for jet lag?

    PubMed

    Tortorolo, Francisco; Farren, Florencia; Rada, Gabriel

    2015-01-01

    Jet lag syndrome is an exogenous circadian rhythm sleep disorder, frequently reported in travelers who cross multiple time zones in a short period of time. Oral melatonin -a pineal neurohormone normally produced during darkness and responsible for regulating the body's circadian rhythms- has been used as treatment for this condition. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including 11 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the use of oral melatonin probably reduces symptoms associated with jet lag syndrome. It is not clear whether its use produces adverse effects; however, these would be probably mild. PMID:26731279

  12. Clinical aspects of melatonin.

    PubMed

    Reiter, Russel J; Korkmaz, Ahmet

    2008-11-01

    Melatonin is produced in the human pineal gland, particularly at night, with the circadian rhythm of blood melatonin levels closely paralleling its production within the pineal gland. Light exposure at night, or rapid transmeridian travel severely compromises the circadian production of melatonin. The disturbed melatonin rhythm contributes to jet lag and sleep inefficiency, both of which are improved by melatonin administration. Melatonin is also a highly effective direct free radical scavenger and antioxidant. In this capacity, melatonin reduces experimental cataractogenesis, traumatic injury to the spinal cord and brain, and protects against oxidative damage to neurons and glia in models of stroke, Parkinsonism, and Alzheimer's disease. Additionally, melatonin and its metabolites are highly effective in protecting against ionizing radiation. Finally, melatonin may be a treatment for hypertension. Melatonin's high efficacy, its high safety profile, and its virtual lack of toxicity make it of interest in clinical medicine. PMID:18997997

  13. Nonpineal melatonin in the alligator (Alligator mississippiensis).

    PubMed

    Roth, J J; Gern, W A; Roth, E C; Ralph, C L; Jacobson, E

    1980-10-31

    All living and most fossil representatives of the reptilian subclass Archosauria lack pineal bodies. Arrhythmic, low-level, nonpineal melatonin is present, however, in the blood of Alligator mississippiensis. Although pineal bodies have been implicated in circadian phenomena, these results suggest that arrhytmic melatonin in alligators may not be involved incircadian events and indicate that the pineal is not the only source of the hormone melatonin. The evolutionary loss of the pineal in Archosauria occurred during the Mesozoic, and era noted for its seasonal stability. Arrhythmic melatonin titers inalligators and pineal loss in alligators and other archosaurs may be related to Mesozoic seasonal stability.

  14. [Morphofunctional and molecular bases of pineal gland aging].

    PubMed

    Khavinson, V Kh; Lin'kova, N S

    2012-01-01

    The review analyzed morphology, molecular and functional aspects of pineal gland aging and methods of it correction. The pineal gland is central organ, which regulates activity of neuroimmunoendocrine, antioxidant and other organisms systems. Functional activity of pineal gland is discreased at aging, which is the reason of melatonin level changing. The molecular and morphology research demonstrated, that pineal gland hadn't strongly pronounced atrophy at aging. Long-term experience showed, that peptides extract of pineal gland epithalamin and synthetic tetrapeptide on it base epithalon restored melatonin secretion in pineal gland and had strong regulatory activity at neuroimmunoendocrine and antioxidant organism systems.

  15. Melatonin prevents neural tube defects in the offspring of diabetic pregnancy.

    PubMed

    Liu, Shangming; Guo, Yuji; Yuan, Qiuhuan; Pan, Yan; Wang, Liyan; Liu, Qian; Wang, Fuwu; Wang, Jingjing; Hao, Aijun

    2015-11-01

    Melatonin, an endogenous neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. However, its protective role on the neural tube defects (NTDs) was not very clear. The aim of this study was to investigate the effects of melatonin on the incidence of NTDs (including anencephaly, encephalocele, and spina bifida) of offspring from diabetic pregnant mice as well as its underlying mechanisms. Pregnant mice were given 10 mg/kg melatonin by daily i.p. injection from embryonic day (E) 0.5 until being killed on E11.5. Here, we showed that melatonin decreased the NTDs (especially exencephaly) rate of embryos exposed to maternal diabetes. Melatonin stimulated proliferation of neural stem cells (NSCs) under hyperglycemic condition through the extracellular regulated protein kinases (ERK) pathway. Furthermore, as a direct free radical scavenger, melatonin decreased apoptosis of NSCs exposed to hyperglycemia. In the light of these findings, it suggests that melatonin supplementation may play an important role in the prevention of neural malformations in diabetic pregnancy. PMID:26475080

  16. [THE CHANGES OF THE INTERRELATIONS OF THE PINEAL GLAND AND THE ORGANS OF THE IMMUNE SYSTEM IN RATS IN RESPONSE TO MELATONIN ADMINISTRATION IN LIGHT REGIME DISTURBANCES].

    PubMed

    Litvinenko, G I; Gritzyk, O B; Mel'nikova, Ye V; Avrorov, P A; Tenditnik, M V; Shurlygina, A V; Trufakin, V A

    2015-01-01

    In this work the correlation analysis was applied to detect the integrated response of the pineal gland (PG) and immunocompetent organs of male Wistar rats in response to administration of melatonin (MT) in light regime disturbances. Animals were kept for 14 days under natural or continuous light (CL). Then for 7 days they received the injections of either 0.9% solution of sodium chloride or MT, after which the rats were decapitated and the mass of their body, PG, thymus and spleen was determined. The lymphocyte subpopulations of the thymus and spleen were studied by flow cytometry. The amount of lipofuscin in PG was assessed by the intensity of autofluorescence in organ frozen sections in 560-600 nm wavelength range. It was found that under the influence of MT, the number of intraorgan correlations in the immune system increased, regardless of the light regime. In animals on CL treated with MT, the number of interorgan connections was reduced, while negative correlations appeared between PG lipofuscin content and cellular composition of the spleen. The synchronizing and adaptogenic effects of MT were most pronounced under conditions of CL.

  17. Search for seasonal rhythmicity of pineal melatonin production in rats under constant laboratory conditions: spectral chronobiological analysis, and relation to solar and geomagnetic variables.

    PubMed

    Bartsch, Hella; Mecke, Dieter; Probst, Hansgeorg; Küpper, Heinz; Seebald, Eckard; Salewski, Lothar; Stehle, Thilo; Bartsch, Christian

    2012-10-01

    Earlier we reported that in a number of experiments pineal melatonin production in rats under constant laboratory conditions displayed seasonal rhythms but subsequently were not always able to confirm this. Since there was no indication under which conditions such rhythms may be present, we performed four consecutive identical experiments with untreated female Sprague-Dawley rats within the same animal room during 1997-2006. Nocturnal urine samples (19-23, 23-3, 3-7 h) were collected at monthly intervals over 494-658 d with 12 animals each in experiments I and II (1997-1999, 1999-2000), 30 animals in experiment III (2002-2004), and 15 in experiment IV (2005-2006). 6-Sulfatoxymelatonin (aMT6s) was measured by ELISA. The excreted aMT6s at each time interval as well as total nocturnal aMT6s-excretion (19-7 h) was submitted to standard statistical analyses as well as to a spectral chronobiological analysis to determine the period lengths of the components involved which was followed by processing with the single cosinor method. Seasonal rhythm components (circannual period length: 360 ± 60 d) were detected in experiment III (2002-2004) for the overall nocturnal excretion as well as for two sub-intervals (23-3 and 3-7 h) and in one night interval of experiment II (23-3 h). Multiple components with mostly short period lengths of around 100 d and some long ones of 500-650 d were found in the other experiments. Systematic MESOR and amplitude variations were observed during the experiments, being highest in experiment II (19-7 h, also 23-3 h and 3-7 h) and lowest in experiments I and IV. These results illustrate that seasonal melatonin rhythms are not a general phenomenon in female laboratory rats indicating an involvement of unknown environmental cues. As an extension of our earlier hypothesis regarding a seasonal Zeitgeber function of the horizontal intensity H of the geomagnetic field showing circannual variations, we assume further modulation by the 11-yrs' sunspot

  18. Mammalian neurohormones: potential significance in reproductive physiology of St. John's wort (Hypericum perforatum L.)?

    NASA Astrophysics Data System (ADS)

    Murch, Susan; Saxena, Praveen

    2002-10-01

    Melatonin and serotonin are indoleamine neurohormones that function as photoperiod signals in many species and have recently been found in St. John's wort, a medicinal plant used in the treatment of depression. There is no known role for melatonin in higher plants but melatonin functions as a signal of changes in photoperiod in other species. In the current study, serotonin and melatonin were quantified during flower development. Higher concentrations of serotonin were found in flower buds at the tetrad stage of microspore development and higher melatonin concentrations were detected during uninucleate mircosporogenesis. Additionally, the regeneration potential of isolated anthers was highest in the same stage that had elevated melatonin concentrations. These data provide the first evidence of the presence of melatonin during flower development and raise many questions about the potential roles of serotonin and melatonin as regulatory molecules in the reproductive flexibility of higher plants.

  19. Melatonin: the dark force.

    PubMed

    Bergstrom, W H; Hakanson, D O

    1998-01-01

    Although the pineal gland was described 2,300 years ago, its functions remained obscure and productive research was limited until 1958, when Lerner and associates defined melatonin. In 1965 Wurtman and Axelrod advanced the "melatonin hypothesis," according to which the pineal gland acts as a transducer responding to changes in circumambient light by changing its rates of melatonin output. Sites and mechanisms of melatonin action are still poorly understood. Two consistent effects are the induction of sleep and an antigonadotropic influence on reproductive structure and behavior. The former is demonstrable and clinically useful in human subjects; the latter has been shown in birds, rodents, and sheep. Alteration of skin color by the contraction of melanophores was effected by pineal extracts before the discovery of melatonin. This phenomenon, seen in reptiles, amphibians, and fish, has received little recent attention. Areas of greater interest and potential importance include the antimitotic effects of melatonin on some types of tumor cells in culture and the apparent in vivo protection of immunocompetent lymphocytes during chronic stress, which reduces the functional capacity of lymphocytes in control rodents. Clinical application of the antimitotic and immunosupportive properties of melatonin seems likely in the near future. Unfortunately, this innocent molecule has been touted in two recent books and many advertisements as an aphrodisiac, rejuvenator, protector against disease, and general wonder-worker. Because interest in melatonin is high, all physicians can expect questions and may have use for the information provided in this review.

  20. The effects of extremely low-frequency magnetic fields on melatonin and cortisol, two marker rhythms of the circadian system

    PubMed Central

    Touitou, Yvan; Selmaoui, Brahim

    2012-01-01

    In the past 30 years the concern that daily exposure to extremely low-frequency magnetic fields (ELF-EMF) (1 to 300 Hz) might be harmful to human health (cancer, neurobehavioral disturbances, etc) has been the object of debate, and has become a public health concern. This has resulted in the classification of ELF-EMF into category 2B, ie, agents that are “possibly carcinogenic to humans” by the International Agency for Research on Cancer. Since melatonin, a neurohormone secreted by the pineal gland, has been shown to possess oncostatic properties, a “melatonin hypothesis” has been raised, stating that exposure to EMF might decrease melatonin production and therefore might promote the development of breast cancer in humans. Data from the literature reviewed here are contradictory. In addition, we have demonstrated a lack of effect of ELF-EMF on melatonin secretion in humans exposed to EMF (up to 20 years' exposure) which rebuts the melatonin hypothesis. Currently, the debate concerns the effects of ELF-EMF on the risk of childhood leukemia in children chronically exposed to more than 0.4 μT. Further research is thus needed to obtain more definite answers regarding the potential deleterious effects of ELF-EMF. PMID:23393415

  1. The effects of extremely low-frequency magnetic fields on melatonin and cortisol, two marker rhythms of the circadian system.

    PubMed

    Touitou, Yvan; Selmaoui, Brahim

    2012-12-01

    In the past 30 years the concern that daily exposure to extremely low-frequency magnetic fields (ELF-EMF) (1 to 300 Hz) might be harmful to human health (cancer, neurobehavioral disturbances, etc) has been the object of debate, and has become a public health concern. This has resulted in the classification of ELF-EMF into category 2B, ie, agents that are "possibly carcinogenic to humans" by the International Agency for Research on Cancer. Since melatonin, a neurohormone secreted by the pineal gland, has been shown to possess oncostatic properties, a "melatonin hypothesis" has been raised, stating that exposure to EMF might decrease melatonin production and therefore might promote the development of breast cancer in humans. Data from the literature reviewed here are contradictory. In addition, we have demonstrated a lack of effect of ELF-EMF on melatonin secretion in humans exposed to EMF (up to 20 years' exposure) which rebuts the melatonin hypothesis. Currently, the debate concerns the effects of ELF-EMF on the risk of childhood leukemia in children chronically exposed to more than 0.4 μT. Further research is thus needed to obtain more definite answers regarding the potential deleterious effects of ELF-EMF.

  2. Two components of the pineal organ in the mink (Mustela vison): their structural similarity to submammalian pineal complexes and calcification.

    PubMed

    Vigh, B; Vigh-Teichmann, I

    1992-12-01

    The pineal complex in the mink (Mustela vison) consists of a larger ventral and a smaller dorsal pineal. Both organs contain pinealocytes, neurons, glial cells, nerve fibers and synapses in an organization characteristic of nervous tissue. The cellular elements are arranged circularly around strait lumina. These lumina correspond to the photoreceptor spaces of submammalian pineals. A 9 + 0-type cilium marks the receptory pole of the pinealocytes which may form an inner-segment-like dendrite terminal in the pineal lumina. The cilia correspond to outer segments which form photoreceptor membrane multiplications in the pineal of submammalians and in certain insectivorous and mustelid mammals (bat, hedgehog, ferret). Axonal processes of the pinealocytes contain synaptic ribbons and terminate on intrapineal neurons of both organs. This pattern represents a neural efferentation of the pineal nervous tissue. The axonal processes of pinealocytes also form neurohormonal endings which pierce the perivascular limiting glial membrane in the ventral as well as in the dorsal pineal. The upper pineal ("epipineal") of the mink may correspond to the parapineal, frontal, or parietal organs of submammalian pineal complexes. Both pineals are encapsulated by the meningeal tissue of the brain stem. Afferent vasomotor axons of the meninges innervate smooth muscle cells of pineal arterioles. There are corpora arenacea in the pineal arachnoid and in the pineal nervous tissue, primarily in the ventral pineal. The localization of calcium ions detected around the membrane of pineal cells by pyroantimonate cytochemistry suggests membrane activity as the source of the calcium ions. The accumulation of calcium by the pinealocytes may be due to their neurosensory character. The mink is the first animal described to have both intrapineal and meningeal concrements like the human pineal. PMID:1295547

  3. The pineal gland from development to function.

    PubMed

    Sapède, Dora; Cau, Elise

    2013-01-01

    The pineal gland is a small neuroendocrine organ whose main and most conserved function is the nighttime secretion of melatonin. In lower vertebrates, the pineal gland is directly photosensitive. In contrast, in higher vertebrates, the direct photosensitivity of the pineal gland had been lost. Rather, the action of this gland as a relay between environmental light conditions and body functions involves reception of light information by the retina. In parallel to this sensory regression, the pineal gland (and its accessory organs) appears to have lost several functions in relation to light and temperature, which are important in lower vertebrate species. In humans, the functions of the pineal gland overlap with the functions of melatonin. They are extremely widespread and include general effects both on cell protection and on more precise functions, such as sleep and immunity. Recently, the role of melatonin has received a considerable amount of attention due to increased cancer risk in shift workers and the discovery that patients suffering from neurodegenerative diseases, autism, or depression exhibit abnormal melatonin rhythms.

  4. Melatonin: a multitasking molecule.

    PubMed

    Reiter, Russel J; Tan, Dun-Xian; Fuentes-Broto, Lorena

    2010-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) has revealed itself as an ubiquitously distributed and functionally diverse molecule. The mechanisms that control its synthesis within the pineal gland have been well characterized and the retinal and biological clock processes that modulate the circadian production of melatonin in the pineal gland are rapidly being unravelled. A feature that characterizes melatonin is the variety of mechanisms it employs to modulate the physiology and molecular biology of cells. While many of these actions are mediated by well-characterized, G-protein coupled melatonin receptors in cellular membranes, other actions of the indole seem to involve its interaction with orphan nuclear receptors and with molecules, for example calmodulin, in the cytosol. Additionally, by virtue of its ability to detoxify free radicals and related oxygen derivatives, melatonin influences the molecular physiology of cells via receptor-independent means. These uncommonly complex processes often make it difficult to determine specifically how melatonin functions to exert its obvious actions. What is apparent, however, is that the actions of melatonin contribute to improved cellular and organismal physiology. In view of this and its virtual absence of toxicity, melatonin may well find applications in both human and veterinary medicine.

  5. A pilot double-blind randomised placebo-controlled dose–response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol

    PubMed Central

    Fernando, Shavi; Osianlis, Tiki; Vollenhoven, Beverley; Wallace, Euan; Rombauts, Luk

    2014-01-01

    Introduction High levels of oxidative stress can have considerable impact on the outcomes of in vitro fertilisation (IVF). Recent studies have reported that melatonin, a neurohormone secreted from the pineal gland in response to darkness, has significant antioxidative capabilities which may protect against the oxidative stress of infertility treatment on gametes and embryos. Early studies of oral melatonin (3–4 mg/day) in IVF have suggested favourable outcomes. However, most trials were poorly designed and none have addressed the optimum dose of melatonin. We present a proposal for a pilot double-blind randomised placebo-controlled dose–response trial aimed to determine whether oral melatonin supplementation during ovarian stimulation can improve the outcomes of assisted reproductive technology. Methods and analyses We will recruit 160 infertile women into one of four groups: placebo (n=40); melatonin 2 mg twice per day (n=40); melatonin 4 mg twice per day (n=40) and melatonin 8 mg twice per day (n=40). The primary outcome will be clinical pregnancy rate. Secondary clinical outcomes include oocyte number/quality, embryo number/quality and fertilisation rate. We will also measure serum melatonin and the oxidative stress marker, 8-hydroxy-2′-deoxyguanosine at baseline and after treatment and levels of these in follicular fluid at egg pick-up. We will investigate follicular blood flow with Doppler ultrasound, patient sleepiness scores and pregnancy complications, comparing outcomes between groups. This protocol has been designed in accordance with the SPIRIT 2013 Guidelines. Ethics and dissemination Ethical approval has been obtained from Monash Health HREC (Ref: 13402B), Monash University HREC (Ref: CF14/523-2014000181) and Monash Surgical Private Hospital HREC (Ref: 14107). Data analysis, interpretation and conclusions will be presented at national and international conferences and published in peer-reviewed journals. Trial registration number ACTRN

  6. Cancer as the main aging factor for humans: the fundamental role of 5-methoxy-tryptamine in reversal of cancer-induced aging processes in metabolic and immune reactions by non-melatonin pineal hormones.

    PubMed

    Lissoni, Paolo; Messina, Giuseppina; Rovelli, Franco

    2012-12-01

    Aging and advanced cancer are characterized by similar neuroendocrine and immune deficiencies; the most important of them consist of diminished nocturnal production of the pineal hormone melatonin (MLT) and decreased production of IL-2. At present, however, it is known that the pineal gland may produce indole hormones other than MLT. The most investigated of them is represented by 5-methoxy-tryptamine (5-MTT), which may exert antitumor, anticachectic, and immunomodulating effects under experimental conditions, in addition to those effects produced by MLT itself. In an attempt to obtain some preliminary data in human subjects about the potential therapeutic properties of 5-MTT, three different studies of 5-MTT have been carried out in advanced solid tumor patients. The first study of MLT plus 5-MTT included 14 thrombocytopenic cancer patients who did not respond to MLT alone. In the second study we have compared the clinical efficacy of MLT plus 5-MTT in a group of 25 untreatable metastatic cancer patients to the results obtained in a control group of 25 cancer patients receiving MLT alone. Finally, the third study of MLT plus 5-MTT included 14 untreatable metastatic cancer patients who did not respond to MLT alone. In all of these studies, MLT and 5-MTT were given orally at the level of 20 mg/day in the evening and at 5 mg/day during the period of maximum light. A normalization of platelet number was achieved by MLT plus 5-MTT in 5 of 14 (36%) thrombocytopenic cancer patients who did not respond to MLT alone. The percentage of disease control obtained by MLT plus 5-MTT in untreatable metastatic cancer patients was significantly higher than that achieved by MLT alone (15/25 [60%] vs. 8/25 [32%], P < 0.05). Finally, the association of 5-MTT with MLT induced disease stabilization in 4 of 14 (29%) untreatable metastatic cancer patients who did not respond to MLT alone.

  7. Restricted feeding restores rhythmicity in the pineal gland of arrhythmic suprachiasmatic-lesioned rats.

    PubMed

    Feillet, Céline A; Mendoza, Jorge; Pévet, Paul; Challet, Etienne

    2008-12-01

    In mammals, the rhythmic synthesis of melatonin by the pineal gland is tightly controlled by the master clock located in the suprachiasmatic nuclei (SCN). In behaviourally arrhythmic SCN-lesioned rats, we investigated the effects of daily restricted feeding (RF) on pineal melatonin synthesis. RF restored not only a rhythmic transcription of the rate-limiting enzyme for melatonin biosynthesis [arylalkylamine-N-acetyltransferase (AANAT)] and a rhythmic expression of c-FOS but also a rhythmic synthesis of melatonin in the pineal gland. In control rats without functional SCN and fed ad libitum, a daily immobilization stress did not restore any rhythmicity in the pineal gland. Interestingly, a combination of RF and daily stress prior to the time of food access did not markedly impair AaNat mRNA and c-FOS rhythmicity but did abolish the restoration of rhythmic pineal melatonin. These data indicate that the synchronizing effects of RF on the pineal rhythmicity are not due to, and cannot be mimicked by, high levels of circulating glucocorticoids. In keeping with the multi-oscillatory nature of the circadian system, the rhythmicity of pineal melatonin in mammals, until now an exclusive output of the SCN, can also be controlled by daily feeding cues when the SCN clock is lacking. Thus, the present study demonstrates that daily RF in SCN-lesioned rats provides, probably via sympathetic fibres, synchronizing stimuli strong enough to drive rhythmicity in the pineal gland.

  8. The pineal gland - Its possible roles in human reproduction

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Wurtman, Richard J.

    1988-01-01

    The paper discusses the role of the pineal gland in controlling mammalian reproduction, with particular attention given to the role of melatonin in polyestrus mammals, like humans and laboratory rodents. Evidence is cited indicating the influence of melatonin production and blood content on the age of puberty, the timing of the ovulatory cycle, gonadal steriodogenesis, and patterns of reproductive behavior. It is suggested that abnormal patterns of melatonin might be associated with amenorrhea, anovulation, unexplained infertility, premature menopause, and habitual abortions.

  9. Hypothalamic neurohormones and immune responses

    PubMed Central

    Quintanar, J. Luis; Guzmán-Soto, Irene

    2013-01-01

    The aim of this review is to provide a comprehensive examination of the current literature describing the neural-immune interactions, with emphasis on the most recent findings of the effects of neurohormones on immune system. Particularly, the role of hypothalamic hormones such as Thyrotropin-releasing hormone (TRH), Corticotropin-releasing hormone (CRH) and Gonadotropin-releasing hormone (GnRH). In the past few years, interest has been raised in extrapituitary actions of these neurohormones due to their receptors have been found in many non-pituitary tissues. Also, the receptors are present in immune cells, suggesting an autocrine or paracrine role within the immune system. In general, these neurohormones have been reported to exert immunomodulatory effects on cell proliferation, immune mediators release and cell function. The implications of these findings in understanding the network of hypothalamic neuropeptides and immune system are discussed. PMID:23964208

  10. The role of melatonin in multiple sclerosis, Huntington's disease and cerebral ischemia.

    PubMed

    Escribano, Begoña M; Colín-González, Ana L; Santamaría, Abel; Túnez, Isaac

    2014-01-01

    Melatonin is produced and released by the pineal gland in a circadian rhythm. This neurohormone has proven to be an antioxidant and anti-inflammatory molecule able to reduce or mitigate cell damage associated with oxidative stress and inflammation, and this phenomenon underlies neurodegenerative disorders. These facts have drawn attention to this indole, triggering interest in evaluating its changes and in its relationship to the processes indicated, and analyzing its role in the mechanisms involved at the onset and development of neurodegenerative diseases, as well as its therapeutic potential. Multiple sclerosis, the most common cause of non-traumatic disability in young adults, is a chronic neuroinflammatory disease, characterized by demyelination, inflammation, and neuronal and oxidative damage. In its early diagnosis, it often requires a differential screening with other neurodegenerative diseases with similar symptoms, such as Huntington's disease, an autosomal dominant disorder. The onset of both diseases occurs in the second or third decade of life. On the other hand, cerebral ischemia is a major cause of human disability all over the world. Although a cerebral stroke can occur as the result of different damaging insults, severe ischemia produces the death of neuronal cells within minutes. Changes in melatonin levels have been observed in these processes (Huntington's disease, multiple sclerosis and cerebral ischemia) as part of their pathogenic features. This review aims to update and discuss the role played by melatonin during neurodegenerative processes, specifically in multiple sclerosis, Huntington's disease, and cerebral ischemia, and its possible therapeutic use. We also provide readers with an update on the many neuroprotective mechanisms exerted by this neurohormone in the Central Nervous System. PMID:25106623

  11. Melatonin in animal models

    PubMed Central

    Pévet, Paul

    2003-01-01

    Melatonin is a hormone synthesized and secreted during the night by the pineal gland. Its production is mainly driven by the Orcadian clock, which, in mammals, is situated in the suprachiasmatic nucleus of the hypothalamus. The melatonin production and release displays characteristic daily (nocturnal) and seasonal patterns (changes in duration proportional to the length of the night) of secretion. These rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes. In mammals, the role of melatonin in the control of seasonality is well documented, and the sites and mechanisms of action involved are beginning to be identified. The exact role of the hormone in the diurnal (Orcadian) timing system remains to be determined. However, exogenous melatonin has been shown to affect the circadian clock. The molecular and cellular mechanisms involved in this well-characterized “chronobiotic” effect have also begun to be characterized. The circadian clock itself appears to be an important site for the entrapment effect of melatonin and the presence of melatonin receptors appears to be a prerequisite. A better understanding of such “chronobiotic” effects of melatonin will allow clarification of the role of endogenous melatonin in circadian organization. PMID:22033558

  12. Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism.

    PubMed

    Laranjeira-Silva, Maria Fernanda; Zampieri, Ricardo A; Muxel, Sandra M; Floeter-Winter, Lucile Maria; Markus, Regina P

    2015-11-01

    Acute inflammatory responses induced by bacteria or fungi block nocturnal melatonin synthesis by rodent pineal glands. Here, we show Leishmania infection does not impair daily melatonin rhythm in hamsters. Remarkably, the attenuated parasite burden and lesion progression in hamsters infected at nighttime was impaired by blockage of melatonin receptors with luzindole, whereas melatonin treatment during the light phase attenuated Leishmania infection. In vitro studies corroborated in vivo observations. Melatonin treatment reduced macrophage expression of Cat-2b, Cat1, and ArgI, genes involved in arginine uptake and polyamine synthesis. Indeed, melatonin reduced macrophage arginine uptake by 40%. Putrescine supplementation reverted the attenuation of infectivity by melatonin indicating that its effect was due to the arrest of parasite replication. This study shows that the Leishmania/host interaction varies in a circadian manner according to nocturnal melatonin pineal synthesis. Our results provide new data regarding Leishmania infectiveness and show new approaches for applying agonists of melatonin receptors in Leishmaniasis therapy.

  13. Circadian clock system in the pineal gland.

    PubMed

    Fukada, Yoshitaka; Okano, Toshiyuki

    2002-02-01

    The pineal gland is a neuroendocrine organ that functions as a central circadian oscillator in a variety of nonmammalian vertebrates. In many cases, the pineal gland retains photic input and endocrinal-output pathways both linked tightly to the oscillator. This contrasts well with the mammalian pineal gland equipped only with the output of melatonin production that is subject to neuronal regulation by central circadian oscillator located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Molecular studies on animal clock genes were performed first in Drosophila and later developed in rodents. More recently, clock genes such as Per, Cry, Clock, and Bmal have been found in a variety of vertebrate clock structures including the avian pineal gland. The profiles of the temporal change of the clock gene expression in the avian pineal gland are more similar to those in the mammalian SCN rather than to those in the mammalian pineal gland. Avian pineal gland and mammalian SCN seem to share a fundamental molecular framework of the clock oscillator composed of a transcription/translation-based autoregulatory feedback loop. The circadian time-keeping mechanism also requires several post-translational events, such as protein translocation and degradation processes, in which protein phosphorylation plays a very important role for the stable 24-h cycling of the oscillator and/or the photic-input pathway for entrainment of the clock. PMID:11890455

  14. The function of very long chain polyunsaturated fatty acids in the pineal gland.

    PubMed

    Catalá, Angel

    2010-02-01

    The mammalian pineal gland is a prominent secretory organ with a high metabolic activity. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. Approximately 25% of the total fatty acids present in the rat pineal lipids are represented by arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). These very long chain polyunsaturated fatty acids play important roles in the pineal gland. In addition to the production of melatonin, the mammalian pineal gland is able of convert these polyunsaturated fatty acids into bioactive lipid mediators. Lipoxygenation is the principal lipoxygenase (LOX) activity observed in the rat pineal gland. Lipoxygenation in the pineal gland is exceptional because no other brain regions express significant LOX activities under normal physiological conditions. The rat pineal gland expresses both 12- and 15-lipoxygenase (LOX) activities, producing 12- and 15-hydroperoxyeicosatetraenoic acid (12- and 15-HpETE) from arachidonic acid and 14- and 17-hydroxydocosahexaenoic acid (14- and 17-HdoHE) from docosahexaenoic acid, respectively. The rat pineal also produces hepoxilins via LOX pathways. The hepoxilins are bioactive epoxy-hydroxy products of the arachidonic acid metabolism via the 12S-lipoxygenase (12S-LOX) pathway. The two key pineal biochemical functions, lipoxygenation and melatonin synthesis, may be synergistically regulated by the status of n-3 essential fatty acids.

  15. Distinct effects of the serotonin-noradrenaline reuptake inhibitors milnacipran and venlafaxine on rat pineal monoamines.

    PubMed

    Muneoka, Katsumasa; Kuwagata, Makiko; Ogawa, Tetsuo; Shioda, Seiji

    2015-06-17

    Monoamine systems are involved in the pathology and therapeutic mechanism of depression. The pineal gland contains large amounts of serotonin as a precursor for melatonin, and its activity is controlled by noradrenergic sympathetic nerves. Pineal diurnal activity and its release of melatonin are relevant to aberrant states observed in depression. We investigated the effects on pineal monoamines of serotonin-noradrenaline reuptake inhibitors, which are widely used antidepressants. Four days of milnacipran treatment led to an increase in noradrenaline and serotonin levels, whereas 4 days of venlafaxine treatment reduced 5-hydroxyindoleacetic acid levels; both agents induced an increase in dopamine levels. Our data suggest that milnacipran increases levels of the precursor for melatonin synthesis by facilitating the noradrenergic regulation of pineal activity and that venlafaxine inhibits serotonin reuptake into noradrenergic terminals on the pineal gland. PMID:26016648

  16. Rhythmic control of endocannabinoids in the rat pineal gland.

    PubMed

    Koch, Marco; Ferreirós, Nerea; Geisslinger, Gerd; Dehghani, Faramarz; Korf, Horst-Werner

    2015-01-01

    Endocannabinoids modulate neuroendocrine networks by directly targeting cannabinoid receptors. The time-hormone melatonin synchronizes these networks with external light condition and guarantees time-sensitive and ecologically well-adapted behaviors. Here, the endocannabinoid arachidonoyl ethanolamide (AEA) showed rhythmic changes in rat pineal glands with higher levels during the light-period and reduced amounts at the onset of darkness. Norepinephrine, the essential stimulus for nocturnal melatonin biosynthesis, acutely down-regulated AEA and other endocannabinoids in cultured pineal glands. These temporal dynamics suggest that AEA exerts time-dependent autocrine and/or paracrine functions within the pineal. Moreover, endocananbinoids may be released from the pineal into the CSF or blood stream.

  17. [Biological potentiality of melatonin].

    PubMed

    Muñoz Barragán, Luciano

    2002-01-01

    The pineal gland is an epithalamic structure whose mission is to integrate incoming environmental information with other types of information deriving from the inner milieu itself of the organism, releasing melatonin, a substance able to elicit responses in the central nervous and endocrine systems. Secreted rhythmically during the scotophase, melatonin is involved in reproductive mechanisms, in cyclically developing nosological. Processes, and in the genesis or maintenance of cerebral biorhythms. Owing to its ability to uptake free radicals produced by cell metabolism, it is a potent antioxidant agent that is able to delay cellular ageing and inhibit cellular proliferation in both experimental and spontaneous tumours. PMID:12812036

  18. The pineal gland and the clinical course of multiple sclerosis.

    PubMed

    Sandyk, R

    1992-01-01

    Clinical, epidemiological, biochemical, immunological, and radiological studies suggest that the pineal gland may be implicated in the pathophysiology of multiple sclerosis (MS). The following communication is concerned with the association among MS, pregnancy, the postpartum period, and melatonin secretion and illustrates, based on a clinical case report, the influence of the pineal gland on the clinical course of MS. This association is noteworthy since MS may worsen during the postpartum period and melatonin secretion is reported to be altered most dramatically by pregnancy and delivery. Since melatonin secretion is cyclical, undergoing diurnal, weekly, seasonal, and annual variations, it is proposed that the pineal gland may be the "prime mover" underlying the spontaneous exacerbations and remissions in MS. PMID:1342015

  19. Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis.

    PubMed

    Pinato, Luciana; da Silveira Cruz-Machado, Sanseray; Franco, Daiane G; Campos, Leila M G; Cecon, Erika; Fernandes, Pedro A C M; Bittencourt, Jackson C; Markus, Regina P

    2015-03-01

    Although melatonin is mainly produced by the pineal gland, an increasing number of extra-pineal sites of melatonin synthesis have been described. We previously demonstrated the existence of bidirectional communication between the pineal gland and the immune system that drives a switch in melatonin production from the pineal gland to peripheral organs during the mounting of an innate immune response. In the present study, we show that acute neuroinflammation induced by lipopolysaccharide (LPS) injected directly into the lateral ventricles of adult rats reduces the nocturnal peak of melatonin in the plasma and induces its synthesis in the cerebellum, though not in the cortex or hippocampus. This increase in cerebellar melatonin content requires the activation of nuclear factor kappa B (NF-κB), which positively regulates the expression of the key enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AA-NAT). Interestingly, LPS treatment led to neuronal death in the hippocampus and cortex, but not in the cerebellum. This privileged protection of cerebellar cells was abrogated when G-protein-coupled melatonin receptors were blocked by the melatonin antagonist luzindole, suggesting that the local production of melatonin protects cerebellar neurons from LPS toxicity. This is the first demonstration of a switch between pineal and extra-pineal melatonin production in the central nervous system following a neuroinflammatory response. These results have direct implications concerning the differential susceptibility of specific brain areas to neuronal death.

  20. Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus—Consequences to Melatonin Dysfunction

    PubMed Central

    Hardeland, Rüdiger

    2013-01-01

    The mammalian circadian system is composed of numerous oscillators, which gradually differ with regard to their dependence on the pacemaker, the suprachiasmatic nucleus (SCN). Actions of melatonin on extra-SCN oscillators represent an emerging field. Melatonin receptors are widely expressed in numerous peripheral and central nervous tissues. Therefore, the circadian rhythm of circulating, pineal-derived melatonin can have profound consequences for the temporal organization of almost all organs, without necessarily involving the melatonin feedback to the suprachiasmatic nucleus. Experiments with melatonin-deficient mouse strains, pinealectomized animals and melatonin receptor knockouts, as well as phase-shifting experiments with explants, reveal a chronobiological role of melatonin in various tissues. In addition to directly steering melatonin-regulated gene expression, the pineal hormone is required for the rhythmic expression of circadian oscillator genes in peripheral organs and to enhance the coupling of parallel oscillators within the same tissue. It exerts additional effects by modulating the secretion of other hormones. The importance of melatonin for numerous organs is underlined by the association of various diseases with gene polymorphisms concerning melatonin receptors and the melatonin biosynthetic pathway. The possibilities and limits of melatonergic treatment are discussed with regard to reductions of melatonin during aging and in various diseases. PMID:23481642

  1. Melatonin and female reproduction.

    PubMed

    Tamura, Hiroshi; Takasaki, Akihisa; Taketani, Toshiaki; Tanabe, Manabu; Lee, Lifa; Tamura, Isao; Maekawa, Ryo; Aasada, Hiromi; Yamagata, Yoshiaki; Sugino, Norihiro

    2014-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is secreted during the dark hours at night by the pineal gland. After entering the circulation, melatonin acts as an endocrine factor and a chemical messenger of light and darkness. It regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It also affects the brain, immune, gastrointestinal, cardiovascular, renal, bone and endocrine functions and acts as an oncostatic and anti-aging molecule. Many of melatonin's actions are mediated through interactions with specific membrane-bound receptors expressed not only in the central nervous system, but also in peripheral tissues. Melatonin also acts through non-receptor-mediated mechanisms, for example serving as a scavenger for reactive oxygen species and reactive nitrogen species. At both physiological and pharmacological concentrations, melatonin attenuates and counteracts oxidative stress and regulates cellular metabolism. Growing scientific evidence of reproductive physiology supports the role of melatonin in human reproduction. This review was conducted to investigate the effects of melatonin on female reproduction and to summarize our findings in this field.

  2. TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway.

    PubMed

    da Silveira Cruz-Machado, Sanseray; Carvalho-Sousa, Claudia Emanuele; Tamura, Eduardo Koji; Pinato, Luciana; Cecon, Erika; Fernandes, Pedro Augusto Carlos Magno; de Avellar, Maria Christina Werneck; Ferreira, Zulma Silva; Markus, Regina Pekelmann

    2010-09-01

    Nuclear factor-kappa B (NFKB), a pivotal player in inflammatory responses, is constitutively expressed in the pineal gland. Corticosterone inhibits pineal NFKB leading to an enhancement of melatonin production, while tumor necrosis factor (TNF) leads to inhibition of Aa-nat transcription and the production of N-acetylserotonin in cultured glands. The reduction in nocturnal melatonin surge favors the mounting of the inflammatory response. Despite these data, there is no clear evidence of the ability of the pineal gland to recognize molecules that signal infection. This study investigated whether the rat pineal gland expresses receptors for lipopolysaccharide (LPS), the endotoxin from the membranes of Gram-negative bacteria, and to establish the mechanism of action of LPS. Here, we show that pineal glands possess both CD14 and toll-like receptor 4 (TLR4), membrane proteins that bind LPS and trigger the NFKB pathway. LPS induced the nuclear translocation of p50/p50 and p50/RELA dimers and the synthesis of TNF. The maximal expression of TNF in cultured glands coincides with an increase in the expression of TNF receptor 1 (TNFR1) in isolated pinealocytes. In addition, LPS inhibited the synthesis of N-acetylserotonin and melatonin. Therefore, the pineal gland transduces Gram-negative endotoxin stimulation by producing TNF and inhibiting melatonin synthesis. Here, we provide evidence to reinforce the idea of an immune-pineal axis, showing that the pineal gland is a constitutive player in the innate immune response.

  3. Gut Melatonin in Vertebrates: Chronobiology and Physiology

    PubMed Central

    Mukherjee, Sourav; Maitra, Saumen Kumar

    2015-01-01

    Melatonin, following discovery in the bovine pineal gland, has been detected in several extra-pineal sources including gastrointestinal tract or gut. Arylalkylamine N-acetyltransferase (AANAT) is the key regulator of its biosynthesis. Melatonin in pineal is rhythmically produced with a nocturnal peak in synchronization with environmental light–dark cycle. A recent study on carp reported first that melatonin levels and intensity of a ~23 kDa AANAT protein in each gut segment also exhibit significant daily variations but, unlike pineal, show a peak at midday in all seasons. Extensive experimental studies ruled out direct role of light–dark conditions in determining temporal pattern of gut melatoninergic system in carp, and opened up possible role of environmental non-photic cue(s) as its synchronizer. Based on mammalian findings, physiological significance of gut-derived melatonin also appears unique because its actions at local levels sharing paracrine and/or autocrine functions have been emphasized. The purpose of this mini review is to summarize the existing data on the chronobiology and physiology of gut melatonin and to emphasize their relation with the same hormone derived in the pineal in vertebrates including fish. PMID:26257705

  4. Effects of 60-Hz electric fields on serotonin metabolism in the rat pineal gland

    SciTech Connect

    Anderson, L.E.; Hilton, D.I.; Phillips, R.D.; Wilson, B.W.; Chess, E.K.

    1982-06-01

    Serotonin and two of its metabolites, melatonin and 5-methoxytryptophol, exhibit circadian rhythmicity in the pineal gland. We recently reported a marked reduction in the normal night-time increase in melatonin concentration in the pineal glands of rats exposed to 60-Hz electric fields. Concomitant with the apparent abolition of melatonin rhythmicity, serotonin-N-acetyl transferase (SNAT) activity was suppressed. We have now conducted studies to determine if abolition of the rhythm in melatonin production in electric-field-exposed rats arises solely from interference in SNAT activity, or if the availability of pineal serotonin is a factor that is affected by exposure. Pineal serotonin concentrations were compared in rats that were either exposed or sham exposed to 65 kV/m for 30 days. Sham-exposed animals exhibited normal diurnal rhythmicity for pineal concentrations of both melatonin and serotonin; melatonin levels increased markedly during the dark phase with a concurrent decrease in serotonin levels. In the exposed animals, however, normal serotonin rhythmicity was abolished; serotonin levels in these animals did not increase during the light period. The conclusion that electric field exposure results in a biochemical alteration in SNAT enzyme activity can be inferred from the loss of both serotonin and melatonin rhythmicity, as well as by direct measurement of SNAT activity itself. 35 references, 3 figures, 1 table.

  5. Is postmenopausal osteoporosis related to pineal gland functions?

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-02-01

    There is currently considerable interest in the pathogenesis of postmenopausal osteoporosis, which is the most common metabolic bone disease. Osteoporosis affects approximately 20 million persons in the United States, 90% of whom are postmenopausal women. Although there is evidence that estrogen deficiency is an important contributory factor, the pathogenesis of osteoporosis is multifactorial and presently poorly understood. There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification. Animal data indicate that pineal melatonin is involved in the regulation of calcium and phosphorus metabolism by stimulating the activity of the parathyroid glands and by inhibiting calcitonin release and inhibiting prostaglandin synthesis. Hence, the pineal gland may function as a "fine tuner" of calcium homeostasis. In the following communication, we propose that the fall of melatonin plasma levels during the early stage of menopause may be an important contributory factor in the development of postmenopausal osteoporosis. Consequently, plasma melatonin levels taken in the early menopause could be used as an indicator or perhaps as a marker for susceptibility to postmenopausal osteoporosis. Moreover, light therapy, administration of oral melatonin (2.5 mg at night) or agents which induce a sustained release of melatonin secretion such as 5-methoxypsoralen, could be useful agents in the prophylaxis and treatment of postmenopausal osteoporosis. Finally, since application of external artificial magnetic fields has been shown to synchronize melatonin secretion in experimental animals and humans, we propose that treatment with artificial magnetic fields may be beneficial for postmenopausal osteoporosis. PMID:1305608

  6. Sympathetic neural control of indoleamine metabolism in the rat pineal gland

    NASA Technical Reports Server (NTRS)

    Lynch, H. J.; Hsuan, M.; Wurtman, R. J.

    1975-01-01

    The mechanisms responsible for the acceleration in rat pineal biosynthetic activity in response to prolonged exposure to darkness or to immobilization were investigated in animals whose pineals were surgically denervated. Some animals were adrenalectomized to remove one potential source of circulating catecholamines, and some were subjected to a partial chemical sympathectomy accomplished by a series of intravenous injections of 6-hydroxydopamine. Results suggest that N-acetyltransferase (NAT) activity can be enhanced either by release of norepinephrine from sympathetic terminals within the pineal or from sympathetic nerve terminals elsewhere. The stress of immobilization stimulates the pineal by increasing circulating catecholamines. Photic control of pineal function requires intact pineal sympathetic innervation, since the onset of darkness apparently does not cause a sufficient rise in circulating catecholamines to stimulate the pineal. The present studies suggest that nonspecific stress triggers increased biosynthesis and secretion of melatonin; it is possible that this hormone may participate in mechanisms of adaptation.

  7. Melatonin Receptor Genes in Vertebrates

    PubMed Central

    Li, Di Yan; Smith, David Glenn; Hardeland, Rüdiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

    2013-01-01

    Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. PMID:23712359

  8. Biochemical and hormonal evaluation of pineal glands exposed in vitro to magnetic fields. Final report

    SciTech Connect

    Anderson, L.E.; Leung, F.C.; Miller, D.L.

    1998-11-01

    It has been reported that exposure to extremely low frequency (ELF) magnetic fields can significantly alter pineal melatonin metabolism in vivo. However, whether such changes are due to direct or indirect effects of field exposure has not been clearly demonstrated. The objective of this research project was to examine the effects of magnetic fields on melatonin metabolism in pineal glands in vitro. Chicken pineal glands were cultured in a modified incubator encircled by a magnetic field exposure system. The incubator, that was remote from but attached to a standard laboratory incubator, contained a regulated light source for modulation of the light/dark cycle (12:12 L/D). Pineal glands from 4--6 week old chickens were maintained under 95% O{sub 2}, 5% CO{sub 2} in a static culture system. Because of problems due to contamination and loss of viability of such a system, a perfusion system was developed for EMF studies. Both single and multiple chicken pineal glands were used in the perfusion studies and were kept viable in the perfusion chamber by a continuous flow of medium at 39 C for up to 8 days. Perfusate samples were collected into a fraction collector and were subsequently kept frozen at {minus} 20 C until assays were performed. Melatonin secreted by the cultured pineal glands and released into the medium was measured by a melatonin double antibody radioimmunoassay (RIA) using {sup 125}I-melatonin as the label.

  9. Neuroendocrine mediated effects of electromagnetic-field exposure: Possible role of the pineal gland

    SciTech Connect

    Wilson, W.B.; Stevens, R.G.; Anderson, L.E. )

    1989-01-01

    Reports from recent epidemiological studies have suggested a possible association between extremely low frequently (ELF; including 50- or 60-Hz) electric- and magnetic-field exposure, and increased risk of certain cancers, depression, and miscarriage. ELF field-induced pineal gland dysfunction is a possible etiological factor in these effects. Work in our laboratory and elsewhere has shown that ELF electromagnetic-field exposure can alter the normal circadian rhythm of melatonin synthesis and release in the pineal gland. Consequences of reduced or inappropriately timed melatonin release on the endocrine, neuronal, and immune systems are discussed. Laboratory data linking ELF field exposure to changes in pineal circadian rhythms in both animal and humans are reviewed. The authors suggest that the pineal gland, in addition to being a convenient locus for measuring dyschronogenic effects of ELF field exposure, may play a central role in biological response to these fields via alterations in the melatonin signal.

  10. The rat oocyte synthesises melatonin.

    PubMed

    Sakaguchi, Kenichiro; Itoh, Masanori T; Takahashi, Noriyuki; Tarumi, Wataru; Ishizuka, Bunpei

    2013-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine originally identified in the pineal gland, where it is synthesised enzymatically from serotonin (5-hydroxytryptamine) by the sequential action of arylalkylamine N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT; also known as hydroxyindole O-methyltransferase). Melatonin directly affects ovarian functions and previous studies have suggested that melatonin is synthesised in the ovary. In the present study, we examined whether AANAT and ASMT are expressed in the adult rat ovary. Reverse transcription-polymerase chain reaction analyses demonstrated that both AANAT and ASMT mRNAs are expressed in the ovary. Western blotting for AANAT protein showed that the ovary, like the pineal gland, contains this enzymatic protein with a molecular mass of 24kDa. Immunohistochemistry revealed that the AANAT protein is localised to the oocyte, corpus luteum and medulla, including mast cells. AANAT protein was found in oocytes at all stages of follicular development, and its levels in oocytes increased progressively throughout follicular development. Furthermore, isolated oocytes metabolised exogenous serotonin to melatonin. These findings demonstrate that melatonin is synthesised from serotonin in oocytes. Melatonin synthesised in the oocyte may be implicated in its own growth or maturation, for example, by acting as a calmodulin antagonist or an antioxidant.

  11. The pineal gland and the menstrual cycle.

    PubMed

    Sandyk, R

    1992-04-01

    The menstrual cycle reflects the expression of a cyclical process involving the interaction between the hypothalamic-pituitary axis and the ovaries. This complex process requires an integrated neural and humoral control mechanism. It is now well established that a hypothalamic "transducer" located in the medial basal hypothalamus integrates neural and humoral information and translates it into an oscillatory signal which eventually results in the release of the gonadotropin releasing hormone (GnRH), triggering the secretion of gonadotropins from the pituitary gland. Recent animal studies indicate that melatonin influences the functions of the hypothalamic-pituitary-gonadal axis by modifying the firing frequency of the hypothalamic GnRH pulse generator. Consequently, the pineal gland, through the action of melatonin, may exert an important modulatory effect on the mechanisms controlling menstrual cyclicity. Furthermore, abnormal melatonin functions may be involved in the pathogenesis of several disorders of the menstrual cycle including some forms of hypothalamic amenorrhea such as exercise and malnutrition-induced amenorrhea. Consideration of pineal melatonin functions provides a new dimension into the understanding of the neuroendocrine mechanisms governing the cyclical phenomena of the female reproductive system.

  12. Static and extremely low frequency electromagnetic field exposure: reported effects on the circadian production of melatonin.

    PubMed

    Reiter, R J

    1993-04-01

    The circadian rhythm of melatonin production (high melatonin levels at night and low during the day) in the mammalian pineal gland is modified by visible portions of the electromagnetic spectrum, i.e., light, and reportedly by extremely low frequency (ELF) electromagnetic fields as well as by static magnetic field exposure. Both light and non-visible electromagnetic field exposure at night depress the conversion of serotonin (5HT) to melatonin within the pineal gland. Several reports over the last decade showed that the chronic exposure of rats to a 60 Hz electric field, over a range of field strengths, severely attenuated the nighttime rise in pineal melatonin production; however, more recent studies have not confirmed this initial observation. Sinusoidal magnetic field exposure also has been shown to interfere with the nocturnal melatonin forming ability of the pineal gland although the number of studies using these field exposures is small. On the other hand, static magnetic fields have been repeatedly shown to perturb the circadian melatonin rhythm. The field strengths in these studies were almost always in the geomagnetic range (0.2 to 0.7 Gauss or 20 to 70 mu tesla) and most often the experimental animals were subjected either to a partial rotation or to a total inversion of the horizontal component of the geomagnetic field. These experiments showed that several parameters in the indole cascade in the pineal gland are modified by these field exposures; thus, pineal cyclic AMP levels, N-acetyltransferase (NAT) activity (the rate limiting enzyme in pineal melatonin production), hydroxyindole-O-methyltransferase (HIOMT) activity (the melatonin forming enzyme), and pineal and blood melatonin concentrations were depressed in various studies. Likewise, increases in pineal levels of 5HT and 5-hydroxyindole acetic acid (5HIAA) were also seen in these glands; these increases are consistent with a depressed melatonin synthesis. The mechanisms whereby non

  13. An historical view of the pineal gland and mental disorders.

    PubMed

    López-Muñoz, F; Molina, J D; Rubio, G; Alamo, C

    2011-08-01

    Since Classical Antiquity numerous authors have linked the origin of some mental disorders to physical and functional changes in the pineal gland because of its attributed role in humans as the connection between the material and the spiritual world. The pineal organ was seen as a valve-like structure that regulated the flow of animal spirits through the ventricular system, a hypothesis that took on more vigour during the Middle Ages and the Renaissance. The framework for this theory was "the three cells of the brain", in which the pineal gland was even called the "appendix of thought". The pineal gland could also be associated with the boom, during this period, of certain legends about the "stone of folly". But the most relevant psychopathological role of this organ arrived with Descartes, who proposed that it was the seat of the human soul and controlled communications between the physical body and its surroundings, including emotions. After a period of decline during which it was considered as a mere vestigial remnant of evolution, the link between the pineal gland and psychiatric disorders was definitively highlighted in the 20th century, first with the use of glandular extracts in patients with mental deficiency, and finally with the discovery of melatonin in 1958. The physiological properties of melatonin reawakened interest in the relationship between the pineal gland and mental disorders, fundamentally the affective and sleep disorders, which culminated in the development of new pharmacological agents acting through melatonergic receptors (ramelteon and agomelatine).

  14. 'Melatonin isomer' in wine is not an isomer of the melatonin but tryptophan-ethylester.

    PubMed

    Gardana, Claudio; Iriti, Marcello; Stuknytė, Milda; De Noni, Ivano; Simonetti, Paolo

    2014-11-01

    Melatonin is a neurohormone, chronobiotic, and antioxidant compound found in wine and deriving directly from grapes and/or synthesized by yeast during alcoholic fermentation. In addition, a melatonin isomer has been detected in different foods, wine among them. The special interest for melatonin isomer related to the fact that it was found in greater quantities than melatonin and probably shares some of its biological properties. Despite this, its chemical structure has not yet been defined; although some researchers hypothesize, it could be melatonin with the ethylacetamide group shifted into position N1. Thus, the aim of our study was to identify the structures of the melatonin isomer. For this purpose, melatonin and melatonin isomer in Syrah wine were separated chromatographically by a sub-2 μm particle column and detected by tandem mass spectrometry. The sample was then purified and concentrated by solid-phase extraction, hydrolyzed with alkali or esterase, and substrates and products quantified by UPLC-MS/MS. Moreover, melatonin, melatonin isomer, and their product ions were evaluated by high-resolution mass spectrometry. The amount of melatonin isomer and melatonin in the wine was 84 ± 4 and 3 ± 0 ng/mL, respectively. In the solutions, containing diluted alkali or esterase, melatonin isomer was hydrolyzed in about 8 min. Correspondingly, tryptophan was detected, and its amount increased and reached the maximum concentration in about 8 min. Melatonin concentration was not affected by diluted alkali or esterase. The fragmentation pattern of melatonin isomer was different from that of melatonin but comparable to that of tryptophan-ethylester. Finally, the so-called melatonin isomer identity was verified by cochromatography with authentic standard of tryptophan-ethylester.

  15. Melatonin, light and chronobiological disorders.

    PubMed

    Lewy, A J; Sack, R L; Singer, C M

    1985-01-01

    Human plasma melatonin concentrations can be measured accurately and sensitively by gas chromatography-negative chemical ionization mass spectrometry. With this assay, we have shown that: in rats and in humans, plasma melatonin is exclusively derived from the pineal gland; propranolol and clonidine reduce melatonin levels in human; some blind people appear to have free-running melatonin secretory circadian rhythms; bright light can acutely suppress human melatonin production according to a linear fluence-response relationship; manic-depressive patients appear to be supersensitive to light, even when they are well; melatonin levels are greater in manic patients than in depressed patients; in experiments to test the clock-gate model and the hypothesized phase-response curve, two different effects of light appear to present in humans: an acute suppressant effect (mainly in the evening during long photoperiods) and an entrainment effect (particularly during the morning but also in the evening). When blood is sampled for measuring melatonin levels as a marker for circadian phase position, bright light should be avoided after 5 p.m. (the dim light melatonin onset). Bright-light exposure in the morning appears to advance circadian rhythms, whereas bright-light exposure in the evening appears to delay them. Once a patient has been 'phase typed' (phase-advanced vs. phase-delayed), predictions can be made about whether morning or evening light would be more effective in treating the sleep or mood disorder. PMID:3836816

  16. Melatonin concentrations in the sudden infant death syndrome

    NASA Technical Reports Server (NTRS)

    Sturner, W. Q.; Lynch, H. J.; Deng, M. H.; Gleason, R. E.; Wurtman, R. J.

    1990-01-01

    The melatonin levels in various body fluids of the sudden infant death syndrome (SIDS) infants are compared with those of infants of comparable age who died of other causes to examine a possible relationship between pineal function and SIDS. After adjusting for age differences, cerebrospinal fluid melatonin levels are found to be significantly lower in the SIDS infants. It is suggested that diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.

  17. Melatonin in human preovulatory follicular fluid

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

    1987-01-01

    Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 rain or less after follicular aspiration. All of the follicular fluids contained melatonim, in concentrations substantially higher than those in the corresponding serum. A positive correlation was found between follicular fluid and serum melatonin levels in each woman; these observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

  18. Role of melatonin in embryo fetal development

    PubMed Central

    Voiculescu, SE; Zygouropoulos, N; Zahiu, CD; Zagrean, AM

    2014-01-01

    Melatonin is an indoleamine produced by the pineal gland and secreted in a circadian manner. In the past few decades, research over this topic has been enhanced. Melatonin has many important roles in the human physiology: regulator of the circadian rhythms, sleep inducer, antioxidant, anticarcinogenic. This paper reviews the involvement of melatonin in embryo fetal development. The pineal gland develops completely postpartum, so both the embryo and the fetus are dependent on the maternal melatonin provided transplacentally. Melatonin appears to be involved in the normal outcome of pregnancy beginning with the oocyte quality and finishing with the parturition. Its pregnancy night-time concentrations increase after 24 weeks of gestation, with significantly high levels after 32 weeks. Melatonin receptors are widespread in the embryo and fetus since early stages. There is solid evidence that melatonin is neuroprotective and has a positive effect on the outcome of the compromised pregnancies. In addition, chronodisruption leads to a reproductive dysfunction. Thus, the influence of melatonin on the developing human fetus may not be limited to the entertaining of circadian rhythmicity, but further studies are needed. PMID:25713608

  19. Role of melatonin in embryo fetal development.

    PubMed

    Voiculescu, S E; Zygouropoulos, N; Zahiu, C D; Zagrean, A M

    2014-01-01

    Melatonin is an indoleamine produced by the pineal gland and secreted in a circadian manner. In the past few decades, research over this topic has been enhanced. Melatonin has many important roles in the human physiology: regulator of the circadian rhythms, sleep inducer, antioxidant, anticarcinogenic. This paper reviews the involvement of melatonin in embryo fetal development. The pineal gland develops completely postpartum, so both the embryo and the fetus are dependent on the maternal melatonin provided transplacentally. Melatonin appears to be involved in the normal outcome of pregnancy beginning with the oocyte quality and finishing with the parturition. Its pregnancy night-time concentrations increase after 24 weeks of gestation, with significantly high levels after 32 weeks. Melatonin receptors are widespread in the embryo and fetus since early stages. There is solid evidence that melatonin is neuroprotective and has a positive effect on the outcome of the compromised pregnancies. In addition, chronodisruption leads to a reproductive dysfunction. Thus, the influence of melatonin on the developing human fetus may not be limited to the entertaining of circadian rhythmicity, but further studies are needed.

  20. Melatonin as an Antioxidant for Stroke Neuroprotection.

    PubMed

    Watson, Nate; Diamandis, Theo; Gonzales-Portillo, Chiara; Reyes, Stephanny; Borlongan, Cesar V

    2016-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a hormone derived from the pineal gland that has a wide range of clinical applications. While melatonin was originally assessed as a hormone specializing in regulation of the normal circadian rhythm in mammals, it now has been shown to be an effective free radical scavenger and antioxidant. Current research has focused on central nervous system (CNS) disorders, stroke in particular, for potential melatonin-based therapeutics. As of now, the realm of potential therapy regimens is focused on three main treatments: exogenously delivered melatonin, pineal gland grafting, and melatonin-mediated stem cell therapy. All therapies contain both costs and benefits, and current research is still focused on finding the best treatment plan. While comprehensive research has been conducted, more research regarding the safety of such therapies is needed in order to transition into the clinical level of testing. Antioxidants such as traditional Chinese medicine, (-)-epigallocatechin-3-gallate (EGCG), and lavender oil, which have been used for thousands of years as treatment, are now gaining recognition as effective melatonin treatment alternatives. This review will further discuss relevant studies assessing melatonin-based therapeutics and provide evidence of other natural melatonin treatment alternatives for the treatment of stroke. PMID:26497887

  1. Pineal arylalkylamine N-acetyltransferase (Aanat) gene expression as a target of inflammatory mediators in the chicken.

    PubMed

    Piesiewicz, Aneta; Kedzierska, Urszula; Adamska, Iwona; Usarek, Michal; Zeman, Michal; Skwarlo-Sonta, Krystyna; Majewski, Pawel Marek

    2012-11-01

    Previously, we demonstrated that experimental peritonitis in chickens was attenuated by treatment with exogenous melatonin, while the developing inflammation decreased pineal AANAT activity. This suggested the existence of a bidirectional relationship between the activated immune system and pineal gland function. The aim of the present study was to identify the step(s) in the chicken pineal melatonin biosynthetic pathway that are affected by inflammation. Peritonitis was evoked by i.p. injection of thioglycollate solution, either 2h after the start, or 2h before the end of the light period, and the animals were sacrificed 4h later. The effect of inflammation on the expression of genes encoding enzymes participating in melatonin biosynthesis in the pineal gland, i.e. tryptophan hydroxylase 1 (Tph1), dopa decarboxylase (Ddc), arylalkylamine N-acetyltransferase (Aanat) and acetylserotonin O-methyltransferase (Asmt), was evaluated by qPCR. The pineal and serum melatonin concentration as well as the content of its precursors in the pineal gland were measured, along with the activity of the relevant biosynthetic enzymes. Developing peritonitis caused an increase in the pineal levels of the Tph1 mRNA during the night and the Asmt mRNA during the day, while nocturnal Aanat transcription was reduced. Both the pineal and serum melatonin level and the pineal content of N-acetylserotonin (NAS) were decreased during the night in birds with peritonitis. The amount and activity of pineal AANAT were significantly reduced, while the activity of HIOMT was increased under these experimental conditions. These results indicate that the observed decrease in MEL biosynthesis in chickens with developing inflammation is a result of transcriptional downregulation of the Aanat gene, followed by reduced synthesis and activity of the encoded enzyme.

  2. Daily variation of constitutively activated nuclear factor kappa B (NFKB) in rat pineal gland.

    PubMed

    Cecon, Erika; Fernandes, Pedro A; Pinato, Luciana; Ferreira, Zulma S; Markus, Regina P

    2010-01-01

    In mammals, the production of melatonin by the pineal gland is mainly controlled by the suprachiasmatic nuclei (SCN), the master clock of the circadian system. We have previously shown that agents involved in inflammatory responses, such as cytokines and corticosterone, modulate pineal melatonin synthesis. The nuclear transcription factor NFKB, detected by our group in the rat pineal gland, modulates this effect. Here, we evaluated a putative constitutive role for the pineal gland NFKB pathway. Male rats were kept under 12 h:12 h light-dark (LD) cycle or under constant darkness (DD) condition. Nuclear NFKB was quantified by electrophoretic mobility shift assay on pineal glands obtained from animals killed throughout the day at different times. Nuclear content of NFKB presented a daily rhythm only in LD-entrained animals. During the light phase, the amount of NFKB increased continuously, and a sharp drop occurred when lights were turned off. Animals maintained in a constant light environment until ZT 18 showed diurnal levels of nuclear NFKB at ZT15 and ZT18. Propranolol (20 mg/kg, i.p., ZT 11) treatment, which inhibits nocturnal sympathetic input, impaired nocturnal decrease of NFKB only at ZT18. A similar effect was observed in free-running animals, which secreted less nocturnal melatonin. Because melatonin reduces constitutive NFKB activation in cultured pineal glands, we propose that this indolamine regulates this transcription factor pathway in the rat pineal gland, but not at the LD transition. The controversial results regarding the inhibition of pineal function by constant light or blocking sympathetic neurotransmission are discussed according to the hypothesis that the prompt effect of lights-off is not mediated by noradrenaline, which otherwise contributes to maintaining low levels of nuclear NFKB at night. In summary, we report here a novel transcription factor in the pineal gland, which exhibits a constitutive rhythm dependent on environmental photic

  3. Melatonin-induced glycosaminoglycans augmentation in myocardium remote to infarction.

    PubMed

    Drobnik, J; Tosik, D; Piera, L; Szczepanowska, A; Olczak, S; Zielinska, A; Liberski, P P; Ciosek, J

    2013-12-01

    Elevated levels of collagen as well as transient increases of glycosaminoglycans (GAG) have been shown in the myocardium remote to the infarction. The aim of the study is to observe the effect of melatonin on the accumulation of collagen and GAG in the left ventricle wall, remote to the infarction. A second aim is to determine whether the effect of the pineal indole is mediated by the membrane melatonin receptors of heart fibroblasts. Rats with myocardial infarction induced by ligation of the left coronary artery were treated with melatonin at a dose of 60 μg/100 g b.w. or vehicle (2% ethanol in 0.9% NaCl). The results were compared with an untreated control. In the second part of the study, the fibroblasts from the non-infarcted part of myocardium were isolated and cultured. Melatonin at a range of concentrations from 10(-8) M to 10(-6) M was applied to the fibroblast cultures. In the final part of the study, the influence of luzindole (10(-6) M), the melatonin membrane receptor inhibitor, on melatonin-induced GAG augmentation was investigated. Both collagen and GAG content were measured in the experiment. Melatonin elevated GAG content in the myocardium remote to the infarcted heart. Collagen level was not changed by pineal indoleamine. Fibroblasts isolated from the myocardium varied in shape from fusiform to spindle-shaped. Moreover, the pineal hormone (10(-7)M and 10(-6)M) increased GAG accumulation in the fibroblast culture. Luzindole inhibited melatonin-induced elevation of GAG content at 10(-6)M. Melatonin increased GAG content in the myocardium remote to infarction. This effect was dependent on the direct influence of the pineal indole on the heart fibroblasts. The melatonin-induced GAG elevation is blocked by luzindole, the melatonin membrane receptors inhibitor, indicating a direct effect of this indole.

  4. The pineal gland in human beings: relevance to pediatrics.

    PubMed

    Cavallo, A

    1993-12-01

    Several facts suggest that the pineal gland must have a significant role in human beings: the presence of melatonin secretion from infancy to old age; a circadian secretory pattern similar to that found in animal species in which this gland has well-defined functions; its responsiveness to light; and the presence of melatonin receptors in the hypothalamus. Despite the importance of the pineal gland and melatonin in the reproductive activity of all nonprimate vertebrate species studied, the relationship of melatonin secretion to the activity of the hypothalamic-pituitary-gonadal axis in human beings remains presumptive. Some data suggest a possible pineal-reproductive connection throughout the human lifespan, but new research approaches are needed for a better definition of this connection during normal development and in disorders of the reproductive axis. In addition, recent studies that have applied strictly defined techniques to unravel the masking effects of various behavioral and environmental factors suggest that the pineal gland and melatonin have a fundamental role in the regulation of the human biologic clock. Melatonin concentrations in blood or urine may become a useful marker of the circadian rhythm in disorders of rhythms. Moreover, administration of melatonin in physiologic or pharmacologic doses may have an important application in suppression of the hypothalamic-pituitary-gonadal axis as a contraceptive, and in therapy for disorders of biologic rhythms. Among the latter, of particular interest to the pediatric population will be the potential application of melatonin treatment in establishing or reestablishing circadian rhythms in infants and children maintained for long periods under artificial light conditions, as encountered in intensive care units, and in the treatment of sleep and other rhythm disorders associated with developmental delay or blindness. Further research and approval by the U.S. Food and Drug Administration will be required

  5. Circadian dynamics of the cone-rod homeobox (CRX) transcription factor in the rat pineal gland and its role in regulation of arylalkylamine N-acetyltransferase (AANAT).

    PubMed

    Rohde, Kristian; Rovsing, Louise; Ho, Anthony K; Møller, Morten; Rath, Martin F

    2014-08-01

    The cone-rod homeobox (Crx) gene encodes a transcription factor in the retina and pineal gland. Crx deficiency influences the pineal transcriptome, including a reduced expression of arylalkylamine N-acetyltransferase (Aanat), a key enzyme in nocturnal pineal melatonin production. However, previous functional studies on pineal Crx have been performed in melatonin-deficient mice. In this study, we have investigated the role of Crx in the melatonin-proficient rat pineal gland. The current study shows that pineal Crx transcript levels exhibit a circadian rhythm with a peak in the middle of the night, which is transferred into daily changes in CRX protein. The study further shows that the sympathetic innervation of the pineal gland controls the Crx rhythm. By use of adenovirus-mediated short hairpin RNA gene knockdown targeting Crx mRNA in primary rat pinealocyte cell culture, we here show that intact levels of Crx mRNA are required to obtain high levels of Aanat expression, whereas overexpression of Crx induces Aanat transcription in vitro. This regulatory function of Crx is further supported by circadian analysis of Aanat in the pineal gland of the Crx-knockout mouse. Our data indicate that the rhythmic nature of pineal CRX protein may directly modulate the daily profile of Aanat expression by inducing nighttime expression of this enzyme, thus facilitating nocturnal melatonin synthesis in addition to its role in ensuring a correct tissue distribution of Aanat expression.

  6. Pineal Gland Volume Assessed by MRI and Its Correlation with 6-Sulfatoxymelatonin Levels among Older Men.

    PubMed

    Sigurdardottir, Lara G; Markt, Sarah C; Sigurdsson, Sigurdur; Aspelund, Thor; Fall, Katja; Schernhammer, Eva; Rider, Jennifer R; Launer, Lenore; Harris, Tamara; Stampfer, Meir J; Gudnason, Vilmundur; Czeisler, Charles A; Lockley, Steven W; Valdimarsdottir, Unnur A; Mucci, Lorelei A

    2016-10-01

    The pineal gland produces the hormone melatonin, and its volume may influence melatonin levels. We describe an innovative method for estimating pineal volume in humans and present the association of pineal parenchyma volume with levels of the primary melatonin metabolite, 6-sulfatoxymelatonin. We selected a random sample of 122 older Icelandic men nested within the AGES-Reykjavik cohort and measured their total pineal volume, their parenchyma volume, and the extent of calcification and cysts. For volume estimations we used manual segmentation of magnetic resonance images in the axial plane with simultaneous side-by-side view of the sagittal and coronal plane. We used multivariable adjusted linear regression models to estimate the association of pineal parenchyma volume and baseline characteristics, including 6-sulfatoxymelatonin levels. We used logistic regression to test for differences in first morning urinary 6-sulfatoxymelatonin levels among men with or without cystic or calcified glands. The pineal glands varied in volume, shape, and composition. Cysts were present in 59% of the glands and calcifications in 21%. The mean total pineal volume measured 207 mm(3) (range 65-536 mm(3)) and parenchyma volume 178 mm(3) (range 65-503 mm(3)). In multivariable-adjusted models, pineal parenchyma volume was positively correlated with 6-sulfatoxymelatonin levels (β = 0.52, p < 0.001). Levels of 6-sulfatoxymelatonin did not differ significantly by presence of cysts or calcification. By using an innovative method for pineal assessment, we found pineal parenchyma volume to be positively correlated with 6-sulfatoxymelatonin levels, in line with other recent studies.

  7. Pineal Gland Volume Assessed by MRI and Its Correlation with 6-Sulfatoxymelatonin Levels among Older Men.

    PubMed

    Sigurdardottir, Lara G; Markt, Sarah C; Sigurdsson, Sigurdur; Aspelund, Thor; Fall, Katja; Schernhammer, Eva; Rider, Jennifer R; Launer, Lenore; Harris, Tamara; Stampfer, Meir J; Gudnason, Vilmundur; Czeisler, Charles A; Lockley, Steven W; Valdimarsdottir, Unnur A; Mucci, Lorelei A

    2016-10-01

    The pineal gland produces the hormone melatonin, and its volume may influence melatonin levels. We describe an innovative method for estimating pineal volume in humans and present the association of pineal parenchyma volume with levels of the primary melatonin metabolite, 6-sulfatoxymelatonin. We selected a random sample of 122 older Icelandic men nested within the AGES-Reykjavik cohort and measured their total pineal volume, their parenchyma volume, and the extent of calcification and cysts. For volume estimations we used manual segmentation of magnetic resonance images in the axial plane with simultaneous side-by-side view of the sagittal and coronal plane. We used multivariable adjusted linear regression models to estimate the association of pineal parenchyma volume and baseline characteristics, including 6-sulfatoxymelatonin levels. We used logistic regression to test for differences in first morning urinary 6-sulfatoxymelatonin levels among men with or without cystic or calcified glands. The pineal glands varied in volume, shape, and composition. Cysts were present in 59% of the glands and calcifications in 21%. The mean total pineal volume measured 207 mm(3) (range 65-536 mm(3)) and parenchyma volume 178 mm(3) (range 65-503 mm(3)). In multivariable-adjusted models, pineal parenchyma volume was positively correlated with 6-sulfatoxymelatonin levels (β = 0.52, p < 0.001). Levels of 6-sulfatoxymelatonin did not differ significantly by presence of cysts or calcification. By using an innovative method for pineal assessment, we found pineal parenchyma volume to be positively correlated with 6-sulfatoxymelatonin levels, in line with other recent studies. PMID:27449477

  8. A role of melatonin in neuroectodermal-mesodermal interactions: the hair follicle synthesizes melatonin and expresses functional melatonin receptors.

    PubMed

    Kobayashi, Hiromi; Kromminga, Arno; Dunlop, Thomas W; Tychsen, Birte; Conrad, Franziska; Suzuki, Naoto; Memezawa, Ai; Bettermann, Albrecht; Aiba, Setsuya; Carlberg, Carsten; Paus, Ralf

    2005-10-01

    Since mammalian skin expresses the enzymatic apparatus for melatonin synthesis, it may be an extrapineal site of melatonin synthesis. However, evidence is still lacking that this is really the case in situ. Here, we demonstrate melatonin-like immunoreactivity (IR) in the outer root sheath (ORS) of mouse and human hair follicles (HFs), which corresponds to melatonin, as shown by radioimmunoassay and liquid chromatography/tandem mass spectrometry (LC/MS/MS). The melatonin concentration in organ-cultured mouse skin, mouse vibrissae follicles, and human scalp HFs far exceeds the respective melatonin serum level and is significantly increased ex vivo by stimulation with norepinephrine (NE), the key stimulus for pineal melatonin synthesis. By real-time PCR, transcripts for the melatonin membrane receptor MT2 and for the nuclear mediator of melatonin signaling, retinoid orphan receptor alpha (ROR)alpha, are detectable in murine back skin. Transcript levels for these receptors fluctuate in a hair cycle-dependent manner, and are maximal during apoptosis-driven HF regression (catagen). Melatonin may play a role in hair cycle regulation, since its receptors (MT2 and RORalpha) are expressed in murine skin in a hair cycle-dependent manner, and because it inhibits keratinocyte apoptosis and down-regulates ERalpha expression. Therefore, the HF is both, a prominent extrapineal melatonin source, and an important peripheral melatonin target tissue. Regulated intrafollicular melatonin synthesis and signaling may play a previously unrecognized role in the endogenous controls of hair growth, for example, by modulating keratinocyte apoptosis during catagen and by desensitizing the HF to estrogen signaling. As a prototypic neuroectodermal-mesodermal interaction model, the HF can be exploited for dissecting the obscure role of melatonin in such interactions in peripheral tissues. PMID:16030176

  9. Chronic exposure to 60-Hz electric fields: effects on pineal function in the rat

    SciTech Connect

    Wilson, B.W.; Anderson, L.E.; Hilton, D.I.; Philips, R.D.

    1980-01-01

    As a component of studies to search for effects of 60-Hz electric field exposure on mammalian endocrine function, concentrations of melatonin, 5-methoxytryptophol, and serotonin-N-acetyl transferase activity were measured in the pineal glands of rats exposed or sham-exposed at 65 kV/m for 30 days.In two replicate experiments there were statistically significant differences between exposed and control rats in that the normal nocturnal increase in pineal melatonin content was depressed in the exposed animals. Concentrations of 5-methoxytryptophol were increased in the pineal glands of the exposed groups when compared to sham-exposed controls. An alteration was also observed in serotonin-N-acetyl transferase activity, with lower levels measured in pineal glands from exposed animals.

  10. COSMOS 2044. Experiment K-7-19. Pineal physiology in microgravity: Relation to rat gonadal function

    NASA Technical Reports Server (NTRS)

    Holley, D.; Soliman, M. R. I.; Krasnov, I.; Asadi, H.

    1989-01-01

    It is now known that the pineal organ can interact with many endocrine and nonendocrine tissues in a regulatory fashion. Given its key role in the regulation of melatonin synthesis, its high concentration, and that its levels may persist longer than the more rapidly changing melatonin, it was felt that serotonin might give a more accurate assessment of the effects of microgravity on pineal function following recovery of animals from flight. Five-hydroxyindole acetic acid (5-HIAA), a major metabolite of serotonin metabolism, was also measured. One of the most interesting concomitants to spaceflight and exposure to microgravity has been the disturbing alteration in calcium metabolism and resulting skeletal effects. Given the link between exposure to microgravity and perturbation of calcium metabolism and the fact that the pineal is apparently one of the only soft tissues to calcify, pineal calcium content was examined following spaceflight.

  11. Melatonin and human puberty: current perspectives.

    PubMed

    Cavallo, A

    1993-10-01

    Many studies of melatonin in human puberty are difficult to interpret in light of methodological considerations such as the use of single blood samples collected either during the day or at night; a small number of observations; the failure to include the temporal characteristics of melatonin secretion; the definition of puberty by the use of broad clinical features without use of hormonal markers of puberty; the lack of control for the actual duration and intensity of light exposure during the days preceding the study; and the cross sectional nature of most studies. The few studies that have examined the plasma melatonin rhythm in humans by multiple blood sampling overnight or over 24 hr suggest that normal pubertal development (as well as normal ovarian function) are not linked to alterations in the plasma melatonin profile. There is, however, some evidence to suggest that disorders of the hypothalamic-pituitary-gonadal axis (delayed puberty, precocious puberty, hypothalamic amenorrhea) may be linked to altered plasma melatonin profile, at least in some cases. These findings, taken together with strong evidence for the role of the pineal gland in the reproductive function of other vertebrate species, render unlikely the inference that the pineal gland has no role in the development and function of the human reproductive axis. Thus, one may speculate that a pineal-puberty relation does exist in humans and that the research techniques applied to date have been inadequate to uncover this relation.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Melatonin and hypothalamic-pituitary-gonadal axis.

    PubMed

    Shi, L; Li, N; Bo, L; Xu, Z

    2013-01-01

    Melatonin (N-acetyl-5-methoxy-tryptamine), a principal product of the pineal gland, is produced mainly during the dark phase of the circadian cycle. This hormone plays a crucial role in the regulation of circadian and seasonal changes in various aspects of physiology and neuroendocrine functions. In mammals, melatonin can influence sexual maturation and reproductive functions via activation of its receptors and binding sites in the hypothalamic-pituitary-gonadal (HPG) axis. This review summarizes current knowledge of melatonin on the hypothalamus, pituitary gland, and gonads. We also review recent progress in clinical applications of melatonin or potentials of using melatonin, as a reducer of oxidative stress, to improve reproductive functions for the diseases such as women infertility.

  13. [The influence of melatonin on hair physiology].

    PubMed

    Fischer, T W

    2009-12-01

    Melatonin, the pineal gland hormone and a strong antioxidant, has long been known, particularly in animal-experiment based research and the wool-producing industry, to be a potent regulatory neuroendocrine substance in relation to hair growth, hair color and hair cycle, depending on light periods, seasonal rhythms, environmental factors and reproductive rhythms. Nevertheless, the biological mechanisms of this extremely versatile hormone, especially with regard to human hair follicles, are not fully understood. In recent years, however, essential knowledge has been gained on the melatoninergic system of the skin, melatonin levels in keratinocytes and hair follicles, extrapineal intrafollicular melatonin synthesis and noradrenalin-induced increase in synthesis, as well as hair cycle-dependent expression of the membrane-bound melatonin receptor MT2 and the nuclear receptor RORalpha. Functional data on the growth of human hair both in vitro and in vivo show that melatonin might play an essential role in hair physiology. PMID:19957072

  14. Hepatoprotective actions of melatonin: Possible mediation by melatonin receptors

    PubMed Central

    Mathes, Alexander M

    2010-01-01

    Melatonin, the hormone of darkness and messenger of the photoperiod, is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone’s intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo, and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis, hemorrhagic shock, ischemia/reperfusion, and in numerous models of toxic liver injury. Melatonin’s influence on hepatic antioxidant enzymes and other potentially relevant pathways, such as nitric oxide signaling, hepatic cytokine and heat shock protein expression, are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection, this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy. PMID:21182223

  15. Melatonin production in the sea star Echinaster brasiliensis (Echinodermata).

    PubMed

    Peres, Rafael; Amaral, Fernanda Gaspardo; Marques, Antonio Carlos; Neto, José Cipolla

    2014-04-01

    The primary hormone of the vertebrate pineal gland, melatonin, has been identified broadly throughout the tree of life, in animals, plants, and fungi, supporting a deep evolutionary origin for this signaling molecule. However, some key groups have not been studied. Echinoderms, deuterostome animals, are one of these groups. Herein we study the presence of melatonin and enzymes of its pathway in the sea star Echinaster brasiliensis. We demonstrate that E. brasiliensis produces endogenous melatonin, in the gonads, under a circadian pattern with a nocturnal peak of production. We also show that the enzymes arylalkylamine N-acetyltransferase (AANAT) and tryptophan hydroxylase (TPH) are present and are probably regulating the melatonin production.

  16. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

    PubMed

    Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

    2016-03-15

    Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing.

  17. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

    PubMed

    Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

    2016-03-15

    Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

  18. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging

    PubMed Central

    Paltsev, Michael A.; Polyakova, Victoria O.; Kvetnoy, Igor M.; Anderson, George; Kvetnaia, Tatiana V.; Linkova, Natalia S.; Paltseva, Ekaterina M.; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

    2016-01-01

    Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin A); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

  19. Melatonin involvement in oxidative processes.

    PubMed

    Ianăş, O; Olinescu, R; Bădescu, I

    1991-01-01

    The fact that the pineal gland, by its melatonin (MT) production, responds to environmental light variations (the day-night cycle), being also a modulator of the body adaptation to these conditions, may lead to the assumption of its involvement in the body oxidative processes. The redox capacity of melatonin was followed-up in vitro by the chemiluminescence phenomenon. The system generating chemiluminescence as well as free radicals was made up of luminol and H2O2. Incubation of melatonin in doses of 0.08-0.5 microM/ml with the generating system showed that in doses under 0.25 microM/ml melatonin has a pro-oxidative effect while in doses above this value it has an antioxidative effect. The diagram of the results shows the answer specific to a modulator. The study of the correlation between the dose of melatonin with highest pro-oxidative properties and the various peroxide concentrations in the generating system showed that melatonin gets antioxidative properties with the increase in peroxide concentrations (less than 8 mM/ml). In the presence of a hypothalamic homogenate, which is a stimulant of the chemiluminescence-generating system (PXI = 16), melatonin has a dose-dependent antioxidative effect. Similar results were also obtained by adding tryptophan--a free radicals acceptor (PXI = 0.1) and the substrate in melatonin synthesis to the reaction medium. Melatonin in low concentrations (greater than 0.1 microM/ml) has an antioxidative effect while in higher doses it has a dose-dependent pro-oxidative effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1821072

  20. Pharmacology and function of melatonin receptors

    SciTech Connect

    Dubocovich, M.L.

    1988-09-01

    The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-(125I)iodomelatonin are identical. It is proposed that 2-(125I)iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-(125I)iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references.

  1. Melatonin as a proconvulsive hormone in humans.

    PubMed

    Sandyk, R; Tsagas, N; Anninos, P A

    1992-03-01

    The pineal gland and melatonin exert a major influence in the control of brain electrical activity and have been shown to be involved in seizure and sleep mechanisms. Since pinealectomy has been reported to result in seizures in experimental animals, it is assumed that melatonin has anticonvulsant properties. Indeed, limited studies in humans with temporal lobe epilepsy indicate that melatonin attenuates seizure activity. In the present communication we present evidence, based on magnetoencephalographic (MEG) brain measurements, that melatonin may exert proconvulsive activity in humans as well. The proconvulsive properties of melatonin may explain several phenomena associated with epilepsy such as the increased occurrence of seizures at night when melatonin plasma levels are 5 to 8-fold higher than during the day and the observed exacerbation of seizures premenstrually and during pregnancy as well as the attenuation of seizures in the menopause. Furthermore, our findings suggest that anticonvulsants which decrease melatonin secretion, such as the benzodiazepines, may exert their antiepileptic activity by attenuating nocturnal melatonin secretion. Finally, we propose that patients with nocturnal epilepsy or those experiencing exacerbation of seizures premenstrually may benefit from the administration of agents which block the secretion or action of melatonin. PMID:1342024

  2. [Melatonin in dermatology. Experimental and clinical aspects].

    PubMed

    Fischer, T; Wigger-Alberti, W; Elsner, P

    1999-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a hormone with multiple functions in humans, produced by the pineal gland and stimulated by beta-adrenergic receptors. Serum melatonin levels exhibit a circadian rhythm with low levels during the day, rise in the evening and maximum levels at night between 2 and 4 a.m. Melatonin participates in the regulation of several physiological processes such as seasonal biological rhythm, daily sleep induction, aging and modulation of immunobiological defence reactions. Furthermore, melatonin has a highly lipophilic molecular structure facilitating penetration of cell membranes and serving as an extra- and intracellular free radical scavenger. Melatonin seems to quench mainly hydroxyl radicals, the most damaging of all free radicals. Melatonin may play a role in the etiology and treatment of several dermatoses e.g. atopic eczema, psoriasis and malignant melanoma. The influence of melatonin on hair growth is another aspect. Topical application of melatonin inhibits the development of UV-erythema. Penetration through skin after topical application and oral bioavailability auxit further investigations on the pharmacokinetic and pharmacodynamic actions of melatonin. PMID:10068925

  3. The pineal gland and the mode of onset of schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    Recent studies suggest that abnormal melatonin functions may be implicated in the pathophysiology of schizophrenia. Since there is evidence that the presence of pineal calcification (PC) may relate, among other factors, to disturbances in melatonin secretion, I investigated in 23 chronic institutionalized schizophrenic patients the relationship of PC size on CT scan to the mode of onset of schizophrenia which carries both developmental and prognostic significance. Patients with gradual onset schizophrenia had PC size that was significantly larger than those with sudden onset (8.94 +/- 3.96 mm vs. 4.80 +/- 1.75 mm p < .025). These findings suggest that the nature of onset of schizophrenia may be influenced by the activity of the pineal gland, which may exert a role in the development and prognosis of the illness. PMID:1305641

  4. Pineal region tumors: Clinical symptoms and syndromes.

    PubMed

    Rousselle, C; des Portes, V; Berlier, P; Mottolese, C

    2015-01-01

    The present paper investigates the clinical picture and the different clinical signs that reveal pineal region tumors or appear during the course of the follow-up. Biological malignancy and tumor extension determine the semiology and its setting up mode. Typical endocrine signs, dominated by abnormal puberty development, are frequently a part of the clinical scene. Bifocal or ectopic localization in the hypothalamic-pituitary region is accompanied by other endocrine signs such as ante- or post-pituitary insufficiencies which occur several months or even years after the first neurological signs appear. Due to a mass syndrome and obstructive hydrocephalus, intracranial hypertension signs are frequent but unspecific. A careful ophthalmologic examination is essential to search upward gaze paralysis and other signs of the Parinaud's tetrad or pentad. Midbrain dysfunction, including extrinsic aqueduct stenosis, are also prevalent. Except for abnormal pubertal signs, hyper-melatoninemia (secretory tumors) or a-hypo-melatoninemia (tumors destructing pineal) generally remains dormant. Some patients present sleep problems such as narcolepsy or sleepiness during the daytime as well as behavioral problems. This suggests a hypothalamic extension rather than a true consequence of melatonin secretion anomalies. Similarly, some patients may present signs of a "pinealectomized" syndrome, including (cluster) headaches, tiredness, eventually responsive to melatonin. PMID:24439798

  5. The effect of age and pre-light melatonin concentration on the melatonin sensitivity to dim light.

    PubMed

    Nathan, P J; Burrows, G D; Norman, T R

    1999-05-01

    The hormone melatonin is secreted at night from the pineal gland, with light being a potent inhibitor of its secretion. Age related decreases in plasma melatonin concentrations have indicated that this may be related to pineal calcification with aging. Recently, it was shown that the melatonin sensitivity to light may be a biological marker of bipolar disorder. However, on average, patients were older than the control group in most studies, and it is not known if age has an effect on the melatonin suppression by light. To test this hypothesis, the present study investigated the effect of age on the melatonin sensitivity to dim light (200 lux). Participants were grouped into three age groups. On the testing night, they were placed in a dark room from 21.00 h to 02.30 h. Light exposure was for an hour from midnight to 01.00 h. Blood samples were collected at regular intervals for measurement of plasma melatonin. No significant differences were found in the percentage suppression of melatonin within the age groups defined in the present study (P > 0.5). No correlation was also found between age and percentage suppression of melatonin (r2 = 0.007; P > 0.1). Our results suggest that the melatonin suppression by light (200 lux) is not affected by age. PMID:10435774

  6. A Review of Melatonin, Its Receptors and Drugs

    PubMed Central

    Emet, Mucahit; Ozcan, Halil; Ozel, Lutfu; Yayla, Muhammed; Halici, Zekai; Hacimuftuoglu, Ahmet

    2016-01-01

    After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activity-regulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future. PMID:27551178

  7. A Review of Melatonin, Its Receptors and Drugs.

    PubMed

    Emet, Mucahit; Ozcan, Halil; Ozel, Lutfu; Yayla, Muhammed; Halici, Zekai; Hacimuftuoglu, Ahmet

    2016-06-01

    After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activity-regulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future. PMID:27551178

  8. Melatonin, endocrine pancreas and diabetes.

    PubMed

    Peschke, Elmar

    2008-01-01

    Melatonin influences insulin secretion both in vivo and in vitro. (i) The effects are MT(1)-and MT(2)-receptor-mediated. (ii) They are specific, high-affinity, pertussis-toxin-sensitive, G(i)-protein-coupled, leading to inhibition of the cAMP-pathway and decrease of insulin release. [Correction added after online publication 4 December 2007: in the preceding sentence, 'increase of insulin release' was changed to 'decrease of insulin release'.] Furthermore, melatonin inhibits the cGMP-pathway, possibly mediated by MT(2) receptors. In this way, melatonin likely inhibits insulin release. A third system, the IP(3)-pathway, is mediated by G(q)-proteins, phospholipase C and IP(3), which mobilize Ca(2+) from intracellular stores, with a resultant increase in insulin. (iii) Insulin secretion in vivo, as well as from isolated islets, exhibits a circadian rhythm. This rhythm, which is apparently generated within the islets, is influenced by melatonin, which induces a phase shift in insulin secretion. (iv) Observation of the circadian expression of clock genes in the pancreas could possibly be an indication of the generation of circadian rhythms in the pancreatic islets themselves. (v) Melatonin influences diabetes and associated metabolic disturbances. The diabetogens, alloxan and streptozotocin, lead to selective destruction of beta-cells through their accumulation in these cells, where they induce the generation of ROS. Beta-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. Results suggest that melatonin in pharmacological doses provides protection against ROS. (vi) Finally, melatonin levels in plasma, as well as the arylalkylamine-N-acetyltransferase (AANAT) activity, are lower in diabetic than in nondiabetic rats and humans. In contrast, in the pineal gland, the AANAT mRNA is increased and the insulin receptor mRNA is decreased, which indicates a close interrelationship between insulin and melatonin. PMID:18078445

  9. GABAergic signaling in the rat pineal gland.

    PubMed

    Yu, Haijie; Benitez, Sergio G; Jung, Seung-Ryoung; Farias Altamirano, Luz E; Kruse, Martin; Seo, Jong Bae; Koh, Duk-Su; Muñoz, Estela M; Hille, Bertil

    2016-08-01

    Pinealocytes secrete melatonin at night in response to norepinephrine released from sympathetic nerve terminals in the pineal gland. The gland also contains many other neurotransmitters whose cellular disposition, activity, and relevance to pineal function are not understood. Here, we clarify sources and demonstrate cellular actions of the neurotransmitter γ-aminobutyric acid (GABA) using Western blotting and immunohistochemistry of the gland and electrical recording from pinealocytes. GABAergic cells and nerve fibers, defined as containing GABA and the synthetic GAD67, were identified. The cells represent a subset of interstitial cells while the nerve fibers were distinct from the sympathetic innervation. The GABAA receptor subunit α1 was visualized in close proximity of both GABAergic and sympathetic nerve fibers as well as fine extensions among pinealocytes and blood vessels. The GABAB 1 receptor subunit was localized in the interstitial compartment but not in pinealocytes. Electrophysiology of isolated pinealocytes revealed that GABA and muscimol elicit strong inward chloride currents sensitive to bicuculline and picrotoxin, clear evidence for functional GABAA receptors on the surface membrane. Applications of elevated potassium solution or the neurotransmitter acetylcholine depolarized the pinealocyte membrane potential enough to open voltage-gated Ca(2+) channels leading to intracellular calcium elevations. GABA repolarized the membrane and shut off such calcium rises. In 48-72-h cultured intact glands, GABA application neither triggered melatonin secretion by itself nor affected norepinephrine-induced secretion. Thus, strong elements of GABA signaling are present in pineal glands that make large electrical responses in pinealocytes, but physiological roles need to be found.

  10. Melatonin and Parkinson's disease.

    PubMed

    Mayo, Juan C; Sainz, Rosa M; Tan, Dun-Xian; Antolín, Isaac; Rodríguez, Carmen; Reiter, Russel J

    2005-07-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. It is characterized by a progressive loss of dopamine in the substantia nigra and striatum. However, over 70% of dopaminergic neuronal death occurs before the first symptoms appear, which makes either early diagnosis or effective treatments extremely difficult. Only symptomatic therapies have been used, including levodopa (l-dopa), to restore dopamine content; however, the use of l-dopa leads to some long-term pro-oxidant damage. In addition to a few specific mutations, oxidative stress and generation of free radicals from both mitochondrial impairment and dopamine metabolism are considered to play critical roles in PD etiology. Thus, the use of antioxidants as an important co-treatment with traditional therapies for PD has been suggested. Melatonin, or N-acetyl-5-methoxy-tryptamine, an indole mainly produced in the pineal gland, has been shown to have potent endogenous antioxidant actions. Because neurodegenerative disorders are mainly caused by oxidative damage, melatonin has been tested successfully in both in vivo and in vitro models of PD. The present review provides an up-to-date account of the findings and mechanisms involved in neuroprotection of melatonin in PD.

  11. Role of melatonin in upper gastrointestinal tract.

    PubMed

    Konturek, S J; Konturek, P C; Brzozowski, T; Bubenik, G A

    2007-12-01

    Melatonin, an indole formed enzymatically from L-tryptophan, is the most versatile and ubiquitous hormone molecule produced not only in all animals but also in some plants. This review focuses on the role of melatonin in upper portion of gastrointestinal tract (GIT), including oral cavity, esophagus, stomach and duodenum, where this indole is generated and released into the GIT lumen and into the portal circulation to be uptaken, metabolized by liver and released with bile into the duodenum. The biosynthetic steps of melatonin with two major rate limiting enzymes, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming tryptophan to melatonin, originally identified in pinealocytes have been also detected in entero-endocrine (EE) cells of GIT wall, where this indole may act via endocrine, paracrine and/or luminal pathway through G-protein coupled receptors. Melatonin in GIT was shown to be generated in about 500 times larger amounts than it is produced in pineal gland. The production of melatonin by pineal gland shows circadian rhythm with high night-time peak, especially at younger age, followed by the fall during the day-light time. As a highly lipophilic substance, melatonin reaches all body cells within minutes, to serve as a convenient circadian timing signal for alteration of numerous body functions.. Following pinealectomy, the light/dark cycle of plasma melatonin levels disappears, while its day-time blood concentrations are attenuated but sustained mainly due to its release from the GIT. After oral application of tryptophan, the plasma melatonin increases in dose-dependent manner both in intact and pinealectomized animals, indicating that extrapineal sources such as GIT rather than pineal gland are the major producers of this indole. In the upper portion of GIT, melatonin exhibits a wide spectrum of activities such as circadian entrainment, free radicals scavenging activity, protection of mucosa against

  12. Redox capacity of the pineal gland in rats. Effect of castration.

    PubMed

    Ianăs, O; Olinescu, R; Bădescu, I

    1993-01-01

    The day/night cycle-induced effects, and the effect of castration on pineal oxidative potential in rats, were studied herein. Experiments were made in adult and castrated Wistar rats kept under normal light conditions during winter (on December and January). Castration was performed 72 hrs before sacrification. Groups of 6 intact or castrated animals were sacrificed at 4 hr-intervals during 24 hrs (the day/night cycle). Blood and pineal were then taken. Peroxides and total pineal antioxidants in plasma and pineal homogenate were assessed by chemiluminescence. The results obtained prove that photoperiod is involved in the organism oxidative potential, and that pineal is involved in the diurnal rhythm of this potential. Pineal peroxide and antioxidative concentrations show circadian variations with minimum and maximal values during the day or the night, which are also reflected at the plasma level. In the first half of the morning are registered increased peroxide and decreased antioxidative levels while at night the diagrams are reversed. As compared to the intact group, in the castrated one antioxidants and peroxides maintain their biorhythms but their concentrations are significantly changed. The diagram of pineal peroxides in the castrated group is situated above that of the intact one, with statistically significant differences only at midday (12:00). Taking into account the antioxidative characteristics of melatonin, one can suppose that maximum pineal antioxidative levels during the night might be due to maximum concentrations of nocturnal melatonin. The significant increase in peroxide concentration and the decrease in antioxidants after castration would partly explain the physiologic status of the elderly with decreased melatonin production and increased oxidative processes. PMID:7697061

  13. Redox capacity of the pineal gland in rats. Effect of castration.

    PubMed

    Ianăs, O; Olinescu, R; Bădescu, I

    1993-01-01

    The day/night cycle-induced effects, and the effect of castration on pineal oxidative potential in rats, were studied herein. Experiments were made in adult and castrated Wistar rats kept under normal light conditions during winter (on December and January). Castration was performed 72 hrs before sacrification. Groups of 6 intact or castrated animals were sacrificed at 4 hr-intervals during 24 hrs (the day/night cycle). Blood and pineal were then taken. Peroxides and total pineal antioxidants in plasma and pineal homogenate were assessed by chemiluminescence. The results obtained prove that photoperiod is involved in the organism oxidative potential, and that pineal is involved in the diurnal rhythm of this potential. Pineal peroxide and antioxidative concentrations show circadian variations with minimum and maximal values during the day or the night, which are also reflected at the plasma level. In the first half of the morning are registered increased peroxide and decreased antioxidative levels while at night the diagrams are reversed. As compared to the intact group, in the castrated one antioxidants and peroxides maintain their biorhythms but their concentrations are significantly changed. The diagram of pineal peroxides in the castrated group is situated above that of the intact one, with statistically significant differences only at midday (12:00). Taking into account the antioxidative characteristics of melatonin, one can suppose that maximum pineal antioxidative levels during the night might be due to maximum concentrations of nocturnal melatonin. The significant increase in peroxide concentration and the decrease in antioxidants after castration would partly explain the physiologic status of the elderly with decreased melatonin production and increased oxidative processes.

  14. Mood disorders, circadian rhythms, melatonin and melatonin agonists.

    PubMed

    Quera Salva, M A; Hartley, S

    2012-01-01

    Recent advances in the understanding of circadian rhythms have led to an interest in the treatment of major depressive disorder with chronobiotic agents. Many tissues have autonomous circadian rhythms, which are orchestrated by the master clock, situated in the suprachiasmatic nucleus (SNC). Melatonin (N-acetyl-5-hydroxytryptamine) is secreted from the pineal gland during darkness. Melatonin acts mainly on MT1 and MT2 receptors, which are present in the SNC, regulating physiological and neuroendocrine functions, including circadian entrainment, referred to as the chronobiotic effet. Circadian rhythms has been shown to be either misaligned or phase shifted or decreased in amplitude in both acute episodes and relapse of major depressive disorder (MDD) and bipolar disorder. Manipulation of circadian rhythms either using physical treatments (such as high intensity light) or behavioral therapy has shown promise in improving symptoms. Pharmacotherapy using melatonin and pure melatonin receptor agonists, while improving sleep, has not been shown to improve symptoms of depression. A novel antidepressant, agomelatine, combines 5HT2c antagonist and melatonin agonist action, and has shown promise in both acute treatment of MDD and in preventing relapse.

  15. Melatonin: a "Higgs boson" in human reproduction.

    PubMed

    Dragojevic Dikic, Svetlana; Jovanovic, Ana Mitrovic; Dikic, Srdjan; Jovanovic, Tomislav; Jurisic, Aleksandar; Dobrosavljevic, Aleksandar

    2015-02-01

    As the Higgs boson could be a key to unlocking mysteries regarding our Universe, melatonin, a somewhat mysterious substance secreted by the pineal gland primarily at night, might be a crucial factor in regulating numerous processes in human reproduction. Melatonin is a powerful antioxidant which has an essential role in controlling several physiological reactions, as well as biological rhythms throughout human reproductive life. Melatonin, which is referred to as a hormone, but also as an autocoid, a chronobiotic, a hypnotic, an immunomodulator and a biological modifier, plays a crucial part in establishing homeostatic, neurohumoral balance and circadian rhythm in the body through synergic actions with other hormones and neuropeptides. This paper aims to analyze the effects of melatonin on the reproductive function, as well as to shed light on immunological and oncostatic properties of one of the most powerful hormones.

  16. Potency of Melatonin in Living Beings

    PubMed Central

    Choi, Donchan

    2013-01-01

    Living beings are surrounded by various changes exhibiting periodical rhythms in environment. The environmental changes are imprinted in organisms in various pattern. The phenomena are believed to match the external signal with organisms in order to increase their survival rate. The signals are categorized into circadian, seasonal, and annual cycles. Among the cycles, the circadian rhythm is regarded as the most important factor because its periodicity is in harmony with the levels of melatonin secreted from pineal gland. Melatonin is produced by the absence of light and its presence displays darkness. Melatonin plays various roles in creatures. Therefore, this review is to introduce the diverse potential ability of melatonin in manifold aspects in living organism. PMID:25949131

  17. Melatonin: Nature's most versatile biological signal?

    PubMed

    Pandi-Perumal, S R; Srinivasan, V; Maestroni, G J M; Cardinali, D P; Poeggeler, B; Hardeland, R

    2006-07-01

    Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin's cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immune-enhancing and oncostatic properties. Its 'chronobiotic' properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or

  18. Melatonin ameliorates chronic mild stress induced behavioral dysfunctions in mice.

    PubMed

    Haridas, Seenu; Kumar, Mayank; Manda, Kailash

    2013-07-01

    Melatonin, a neurohormone, is known to regulate several physiological functions, especially the circadian homeostasis, mood and behavior. Chronic exposure to stress is involved in the etiology of human affective disorders, and depressed patients have been reported to show changes in the circadian rhythms and nocturnal melatonin concentration. The present study was conducted to evaluate a possible beneficial action of chronic night-time melatonin treatment against chronic mild stress (CMS) induced behavioral impairments. As expected in the present study, the stress exposed mice showed reduced weight gain, hedonic deficit, cognitive deficits and decreased mobility in behavioral despair test. Interestingly, CMS exposed mice showed less anxiety. Chronic night-time melatonin administration significantly ameliorated the stress-induced behavioral disturbances, especially the cognitive dysfunction and depressive phenotypes. In conclusion, the present findings suggest the mitigating role of melatonin against CMS-induced behavioral changes, including the cognitive dysfunctions and reaffirm its potential role as an antidepressant.

  19. Pineal calcification in Alzheimer's disease: an in vivo study using computed tomography.

    PubMed

    Mahlberg, Richard; Walther, Sebastian; Kalus, Peter; Bohner, Georg; Haedel, Sven; Reischies, Friedel M; Kühl, Klaus-Peter; Hellweg, Rainer; Kunz, Dieter

    2008-02-01

    Melatonin has been postulated to have diverse properties, acting as an antioxidant, a neuroprotector, or a stabilizer within the circadian timing system, and is thus thought to be involved in the aging process and Alzheimer's disease (AD). We used computed tomography to determine the degree of pineal calcification (DOC), an intra-individual melatonin deficit marker, as well as the size of uncalcified pineal tissue, in 279 consecutive memory clinic outpatients (AD: 155; other dementia: 25; mild cognitive impairment: 33; depression: 66) and 37 age-matched controls. The size of uncalcified pineal tissue in patients with AD (mean 0.15 cm(2) [S.D. 0.24]) was significantly smaller than in patients with other types of dementia (0.26 [0.34]; P=0.038), with depression (0.28 [0.34]; P=0.005), or in controls (0.25 [0.31]; P=0.027). Additionally, the DOC in patients with AD (mean 76.2% [S.D. 26.6]) was significantly higher than in patients with other types of dementia (63.7 [34.7]; P=0.042), with depression (60.5 [33.8]; P=0.001), or in controls (64.5 [30.6]; P=0.021). These two findings may reflect two different aspects of melatonin in AD. On the one hand, the absolute amount of melatonin excretion capability, as indicated by uncalcified pineal volume, refers to the antioxidant properties of melatonin. On the other hand, the relative reduction in melatonin production capability in the individual, as indicated by DOC, refers to the circadian properties of melatonin. PMID:17097768

  20. Pineal gland function is required for colon antipreneoplastic effects of physical exercise in rats.

    PubMed

    Frajacomo, F T T; de Paula Garcia, W; Fernandes, C R; Garcia, S B; Kannen, V

    2015-10-01

    Light-at-night exposure enhances the risk of cancer. Colon cancer is among the most dangerous tumors affecting humankind. Physical exercise has shown positive effects against colon cancer. Here, we investigated whether pineal gland modulates antipreneoplastic effects of physical exercise in the colon. Surgical and non-surgical pineal impairments were performed to clarify the relationship between the pineal gland activity and manifestation of colonic preneoplastic lesions. Next, a progressive swimming training was applied in rats exposed or not to either non-surgical pineal impairment or carcinogen treatment for 10 weeks. Both surgical and non-surgical pineal impairments increased the development of colon preneoplasia. It was further found that impairing the pineal gland function, higher rates of DNA damage were induced in colonic epithelial and enteric glial cells. Physical exercise acted positively against preneoplasia, whereas impairing the pineal function with constant light exposure disrupts its positive effects on the development of preneoplastic lesions in the colon. This was yet related to increased DNA damage in glial cells and enteric neuronal activation aside from serum melatonin levels. Our findings suggest that protective effects of physical exercise against colon cancer are dependent on the pineal gland activity.

  1. Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance.

    PubMed

    Rath, Martin F; Rohde, Kristian; Klein, David C; Møller, Morten

    2013-06-01

    The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function. A working model is proposed for understanding the sequential action of homeobox genes in controlling development and mature circadian function of the mammalian pinealocyte based on knowledge from detailed developmental and daily gene expression analyses in rats, the pineal phenotypes of homebox gene-deficient mice and studies on development of the retinal photoreceptor; the pinealocyte and retinal photoreceptor share features not seen in other tissues and are likely to have evolved from the same ancestral photodetector cell.

  2. [The role of the pineal body in the endocrine control of puberty].

    PubMed

    Aleandri, V; Spina, V; Ciardo, A

    1997-01-01

    The pineal gland plays an important role in reproductive endocrinology. The epiphysis regulates seasonal variations in reproductive function of seasonally breeding animals. In humans, even if they are not seasonal breeders, the role of the pineal in reproductive endocrinology seems to be important as well. It appears to be of particular importance the endocrine control of the gland on pubertal sexual maturation. Even if not all researchers agree, several data suggest that elevated melatonin levels-characteristic of prepubertal age-keep the hypothalamic-pituitary-gonadal axis in quiescence: thus, an inhibitory effect on pubertal development is exerted. Subsequently, the decreasing serum melatonin with advancing age would result in activation of the hypothalamic pulsatile secretion of GnRH- and therefore of the reproductive axis-with consequent onset of pubertal phenomena. The production rate of melatonin does not change with age and no growth in pineal size from 1 to 15 years of age has been demonstrated by nuclear magnetic resonance (NMR) studies. Therefore the decrease of serum melatonin concentrations has been proposed to be due to the increase in body mass or, according to another hypothesis, to be also temporally linked to sexual maturation. Furthermore, recently, it has been suggested in rats that the pineal influences not only the pubertal sexual maturation, but even the gonadal and genital development and function of offspring, already during intrauterine life. Investigations are needed to evaluate this hypothesis in humans.

  3. Evidence for pineal involvement in timing implantation in the western spotted skunk.

    PubMed

    May, R; Mead, R A

    1986-01-01

    Experiments were designed to test the hypothesis that the pineal gland mediates the effects of changing day length and thereby synchronizes implantation within the population of spotted skunks. Intact, sham-superior cervical ganglionectomized (SCGx), SCGx, and SCGx/bilateral orbitally enucleated (B1) pregnant skunks were subjected to a natural photoperiod, and the duration of the preimplantation period was monitored. In a second set of experiments, melatonin was administered to pregnant skunks via two methods to determine whether or not this pineal hormone would mimic the effects of short day photoperiods or B1 on duration of the preimplantation period. Bilateral SCGx, which presumably denervated the pineal, had no effect on the average duration of the preimplantation period (232 +/- 57 vs. 199 +/- 6 days). However, SCGx reversed the inhibitory effect of B1 on implantation as SCGx/B1 animals had an average duration of the preimplantation period that was not significantly different from intact controls (262 +/- 46 vs. 214 +/- 11 days) but was significantly shortened in comparison to enucleated animals (262 +/- 46 vs. 316 +/- 45 days). Melatonin significantly lengthened the duration of the preimplantation period in animals receiving either daily afternoon injections of melatonin or those receiving melatonin Silastic capsule implants. These results are consistent with the hypothesis that the pineal gland synchronizes photoperiod-induced blastocyst implantation in the western spotted skunk.

  4. Pineal gland volume in primary insomnia and healthy controls: a magnetic resonance imaging study.

    PubMed

    Bumb, Jan M; Schilling, Claudia; Enning, Frank; Haddad, Leila; Paul, Franc; Lederbogen, Florian; Deuschle, Michael; Schredl, Michael; Nolte, Ingo

    2014-06-01

    Little is known about the relation between pineal volume and insomnia. Melatonin promotes sleep processes and, administered as a drug, it is suitable to improve primary and secondary sleep disorders in humans. Recent magnetic resonance imaging studies suggest that human plasma and saliva melatonin levels are partially determined by the pineal gland volume. This study compares the pineal volume in a group of patients with primary insomnia to a group of healthy people without sleep disturbance. Pineal gland volume (PGV) was measured on the basis of high-resolution 3 Tesla MRI (T1-magnetization prepared rapid gradient echo) in 23 patients and 27 controls, matched for age, gender and educational status. Volume measurements were performed conventionally by manual delineation of the pineal borders in multi-planar reconstructed images. Pineal gland volume was significantly smaller (P < 0.001) in patients (48.9 ± 26.6 mm(3) ) than in controls (79 ± 30.2 mm(3) ). In patients PGV correlated negatively with age (r = -0.532; P = 0.026). Adjusting for the effect of age, PGV and rapid eye movement (REM) latency showed a significant positive correlation (rS  = 0.711, P < 0.001) in patients. Pineal volume appears to be reduced in patients with primary insomnia compared to healthy controls. Further studies are needed to clarify whether low pineal volume is the basis or the consequence of functional sleep changes to elucidate the molecular pathology for the pineal volume loss in primary insomnia.

  5. Pineal organ-like organization of the retina in megachiroptean bats.

    PubMed

    Fejér, Z; Haldar, C; Ghosh, M; Frank, L C; Szepessy, Z; Szél, A; Manzano e Silva, M J; Vigh, B

    2001-01-01

    Phylogenetically originated from photoreceptive structures, the pineal organ adapts the organism to circadian and circannual light periodicity of the environment, while the retina develops to a light-based locator. Bats have a nocturnal life and an echolocator orientation presumably modifying the task of photoreception. Looking for morphological basis of the special functions, in the present work we compared the fine structure and immunocytochemistry of the retina and pineal organ in micro- and megacrochiroptean bats. We found that there is a high similarity between the retina and pineal organ in megachiropterans when compared to other species investigated so far. Besides of photoreceptor derived pinealocytes, the pineal organ of both micro- and megachiropterans contain intrapineal neurons and/or ganglionic cells as well as glial cells. Like spherules and pedicles of retinal photoreceptors, axon-type processes of pinealocytes form synaptic ribbon containig terminals. Similar to retinal photoreceptors and neurons, pinealocytes and pineal neurons contain immunoreactive glutamate and aspartate. In addition, excitatory amino acids accumulate in the pineal neurohormonal endings and might have a role in the hormonal (serotonin?) release of the organ. Concerning the structure of the retina the highest similarity to the organization of the pineal organ was found in the megachiroptean fruit eating bats Cynopterus sphinx and Rusettus niloticus. The retina of these species forms folds and crypts in its photoreceptor layer. This organization is similar to the folds of the pineal wall successively developed during evolution. Since a folded photoreceptor layer is not viable for a photolocator screen in decoding two-dimensional images, we suppose that this peculiar organization of the megachiropteran retina is connected to a "pineal-like" photometer task of the eye needed by these species active at night.

  6. Melatonin improves experimental colitis with sleep deprivation

    PubMed Central

    PARK, YOUNG-SOOK; CHUNG, SOOK-HEE; LEE, SEONG-KYU; KIM, JA-HYUN; KIM, JUN-BONG; KIM, TAE-KYUN; KIM, DONG-SHIN; BAIK, HAING-WOON

    2015-01-01

    Sleep deprivation (SD) is an epidemic phenomenon in modern countries, and its harmful effects are well known. SD acts as an aggravating factor in inflammatory bowel disease. Melatonin is a sleep-related neurohormone, also known to have antioxidant and anti-inflammatory effects in the gastrointestinal tract; however, the effects of melatonin on colitis have been poorly characterized. Thus, in this study, we assessed the measurable effects of SD on experimental colitis and the protective effects of melatonin. For this purpose, male imprinting control region (ICR) mice (n=24) were used; the mice were divided into 4 experimental groups as follows: the control, colitis, colitis with SD and colitis with SD and melatonin groups. Colitis was induced by the administration of 5% dextran sulfate sodium (DSS) in the drinking water for 6 days. The mice were sleep-deprived for 3 days. Changes in body weight, histological analyses of colon tissues and the expression levels of pro-inflammatory cytokines and genes were evaluated. SD aggravated inflammation and these effects were reversed by melatonin in the mice with colitis. In addition, weight loss in the mice with colitis with SD was significantly reduced by the injection of melatonin. Treatment with melatonin led to high survival rates in the mice, in spite of colitis with SD. The levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17, interferon-γ and tumor necrosis factor-α, in the serum of mice were significantly increased by SD and reduced by melatonin treatment. The melatonin-treated group showed a histological improvement of inflammation. Upon gene analysis, the expression of the inflammatory genes, protein kinase Cζ (PKCζ) and calmodulin 3 (CALM3), was increased by SD, and the levels decreased following treatment with melatonin. The expression levels of the apoptosis-related inducible nitric oxide synthase (iNOS) and wingless-type MMTV integration site family, member 5A (Wnt5a) genes was

  7. Melatonin receptors: latest insights from mouse models

    PubMed Central

    Tosini, Gianluca; Owino, Sharon; Guillame, Jean-Luc; Jockers, Ralf

    2014-01-01

    Summary Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications towards type 2 diabetes development, visual functions, sleep disturbances and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models. PMID:24903552

  8. Pineal toxoplasmosis mimicking pineal tumor in an AIDS patient.

    PubMed

    Poon, T P; Behbahani, M; Matoso, I; Kim, B

    1994-07-01

    A pineal mass in a patient with acquired immunodeficiency syndrome (AIDS) is reported. Computed tomography (CT) scan revealed a nodular mass in the pineal region with foci of calcification and obstruction of the aqueduct mimicking a pineal tumor. At autopsy, the brain revealed a well-circumscribed lesion with central necrosis in the pineal region suggestive of toxoplasma and involving the periaqueductal area. Susceptibility of a patient with AIDS to opportunistic infections should be considered. PMID:8064908

  9. Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-01-01

    The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1342018

  10. Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-01-01

    The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. The in vitro maintenance of clock genes expression within the rat pineal gland under standard and norepinephrine-synchronized stimulation.

    PubMed

    Andrade-Silva, Jéssica; Cipolla-Neto, José; Peliciari-Garcia, Rodrigo A

    2014-01-01

    Although the norepinephrine (NE) synchronization protocol was proved to be an important procedure for further modulating in vitro pineal melatonin synthesis, the maintenance of clock genes under the same conditions remained to be investigated. The aim of this study was to investigate the maintenance of the clock genes expression in pineal gland cultures under standard and NE-synchronized stimulation. The glands were separated into three experimental groups: Control, Standard (acute NE-stimulation), and NE-synchronized. The expression of Bmal1, Per2, Cry2, Rev-erbα, the clock controlled gene Dbp and Arylalkylamine-N-acetyltransferase were investigated, as well as melatonin content. No oscillations were observed in the expression of the investigated genes from the control group. Under Standard NE stimulation, the clock genes did not exhibit a rhythmic pattern of expression. However, in the NE-synchronized condition, a rhythmic expression pattern was observed in all cases. An enhancement in pineal gland responsiveness to NE stimulation, reflected in an advanced synthesis of melatonin was also observed. Our results reinforce our previous hypothesis that NE synchronization of pineal gland culture mimics the natural rhythmic release of NE in the gland, increasing melatonin synthesis and keeping the pineal circadian clock synchronized, ensuring the fine adjustments that are relied in the clockwork machinery.

  12. Endocrine rhythms in the brown bear (Ursus arctos): Evidence supporting selection for decreased pineal gland size

    PubMed Central

    Ware, Jasmine V; Nelson, O Lynne; Robbins, Charles T; Carter, Patrick A; Sarver, Brice A J; Jansen, Heiko T

    2013-01-01

    Many temperate zone animals adapt to seasonal changes by altering their physiology. This is mediated in large part by endocrine signals that encode day length and regulate energy balance and metabolism. The objectives of this study were to determine if the daily patterns of two important hormones, melatonin and cortisol, varied with day length in captive brown bears (Ursus arctos) under anesthetized and nonanesthetized conditions during the active (March–October) and hibernation periods. Melatonin concentrations varied with time of day and season in nonanesthetized female bears despite exceedingly low nocturnal concentrations (1–4 pg/mL) in the active season. In contrast, melatonin concentrations during hibernation were 7.5-fold greater than those during the summer in anesthetized male bears. Functional assessment of the pineal gland revealed a slight but significant reduction in melatonin following nocturnal light application during hibernation, but no response to beta-adrenergic stimulation was detected in either season. Examination of pineal size in two bear species bears combined with a phylogenetically corrected analysis of pineal glands in 47 other species revealed a strong relationship to brain size. However, pineal gland size of both bear species deviated significantly from the expected pattern. Robust daily plasma cortisol rhythms were observed during the active season but not during hibernation. Cortisol was potently suppressed following injection with a synthetic glucocorticoid. The results suggest that melatonin and cortisol both retain their ability to reflect seasonal changes in day length in brown bears. The exceptionally small pineal gland in bears may be the result of direct or indirect selection. PMID:24303132

  13. Melatonin influence in ovary transplantation: systematic review.

    PubMed

    Shiroma, M E; Botelho, N M; Damous, L L; Baracat, E C; Soares-Jr, J M

    2016-01-01

    Melatonin is an indolamine produced by the pineal gland and it can exert a potent antioxidant effect. Its free radical scavenger properties have been used to advantage in different organ transplants in animal experiments. Several concentrations and administration pathways have been tested and melatonin has shown encouraging beneficial results in many transplants of organs such as the liver, lungs, heart, pancreas, and kidneys. The objective of the present study was to review the scientific literature regarding the use of melatonin in ovary transplantation. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was carried out using the Cochrane and Pubmed databases and employing the terms 'melatonin' AND 'ovary' AND 'transplantation.' After analysis, 5 articles were extracted addressing melatonin use in ovary transplants and involving 503 animals. Melatonin enhanced various graft aspects like morphology, apoptosis, immunological reaction, revascularization, oxidative stress, and survival rate. Melatonin's antioxidative and antiapoptotic properties seemingly produce positive effects on ovarian graft activity. Despite the promising results, further studies in humans need to be conducted to consolidate its use, as ovary transplantation for fertility preservation is gradually being moved from the experimental stage to a clinical setting. PMID:27287621

  14. Melatonin in human preovulatory follicular fluid

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

    1987-01-01

    Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 min or less after follicular aspiration. All of the follicular fluids contained melatonin, in concentrations (35.6 plus or minus 4.8 (plus or minus SEM) pg/mL) substantially higher than those in the corresponding serum (10.0 plus or minus 1.4 pg/mL). A positive correlation was found between follicular fluid and serum melatonin levels in each woman (r = 0.770; P less than 0.001). These observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

  15. Diurnal rhythm of melatonin binding in the rat suprachiasmatic nucleus

    SciTech Connect

    Laitinen, J.T.; Castren, E.; Vakkuri, O.; Saavedra, J.M.

    1989-03-01

    We used quantitative in vitro autoradiography to localize and characterize 2-/sup 125/I-melatonin binding sites in the rat suprachiasmatic nuclei in relation to pineal melatonin production. In a light:dark cycle of 12:12 h, binding density exhibited significant diurnal variation with a peak at the dark-light transition and a trough 12 hours later. Saturation studies suggested that the decreased binding at light-dark transition might be due to a shift of the putative melatonin receptor to a low affinity state.

  16. Melatonin deficiency hypothesis in delirium: a synthesis of current evidence.

    PubMed

    de Rooij, Sophia E; van Munster, Barbara C

    2013-08-01

    The pineal hormone melatonin plays a major role in circadian sleep-wake rhythm in many mammals, including humans. Patients with acute confusional state or delirium, especially those with underlying cognitive impairment, frequently suffer from sleep disturbances and disturbed circadian rhythm. In this review, an overview is given of delirium and delirium symptoms that correspond with symptoms in dementia, such as sundowning, followed by a presentation of the circadian rhythm disorders in delirium in relation to melatonin deficiency. Finally, this review examines the therapeutic benefit of melatonin treatment in disorders related to delirium and dementia, including the placebo-controlled randomized clinical trials addressing this topic.

  17. [Melatonin: a new wonder drug?].

    PubMed

    Wirz-Justice, A

    1996-10-15

    Melatonin, the hormone of the pineal gland is secreted during the night. It provides temporal information on diurnal and seasonal variation to the brain and the body. It is not a "classical" sleeping pill, and it should not be taken as such. The sole sufficiently investigated indication in humans is the treatment of certain sleep disorders from the group of sleep-wake-rhythm disturbances. These manifest themselves by sleep time of the day, i.e. in shift workers, after flights across time zones and in some blind and aged persons. None of the other promises, i.e. that melatonin conserves youth, prolong life, heals cancer or is a free radicals scavenger, have been confirmed by clinical studies. PMID:8966432

  18. [Melatonin: a new wonder drug?].

    PubMed

    Wirz-Justice, A

    1996-10-15

    Melatonin, the hormone of the pineal gland is secreted during the night. It provides temporal information on diurnal and seasonal variation to the brain and the body. It is not a "classical" sleeping pill, and it should not be taken as such. The sole sufficiently investigated indication in humans is the treatment of certain sleep disorders from the group of sleep-wake-rhythm disturbances. These manifest themselves by sleep time of the day, i.e. in shift workers, after flights across time zones and in some blind and aged persons. None of the other promises, i.e. that melatonin conserves youth, prolong life, heals cancer or is a free radicals scavenger, have been confirmed by clinical studies.

  19. On pineal calcification and its relation to subjective sleep perception: a hypothesis-driven pilot study.

    PubMed

    Kunz, D; Bes, F; Schlattmann, P; Herrmann, W M

    1998-06-30

    We classified the degree of pineal calcification (DOC) into seven groups using cranial Computer Tomography (cCT) and then correlated pineal DOC to chronic subjective sleep-related disturbances as measured by a sleep questionnaire in 36 patients. Analysed by logistic regression models, age and sex were not, but higher pineal DOC was significantly associated with the presence of daytime tiredness (OR = 4.15, 95% CI: 1.63, 10.54) and sleep disturbance (OR = 1.74, 95% CI: 1.10, 2.74). This study provides initial confirmation of the hypothesis that the increasing degree of pineal calcification (DOC) might indicate a decrease of melatonin production, which consecutively might lead to a disturbed circadian rhythmicity in the sleep-wake cycle, with the principal symptom being daytime tiredness. PMID:9754443

  20. Marked rapid alterations in nocturnal pineal serotonin metabolism in mice and rats exposed to weak intermittent magnetic fields

    SciTech Connect

    Lerchl, A.; Nonaka, K.O.; Stokkan, K.A.; Reiter, R.J. )

    1990-05-31

    Adult AMES mice and male Sprague Dawley rats were exposed to an artificial magnetic field, generated by Helmholtz coils. 3.5 hours after the onset of darkness the coils were activated for one hour resulting in an inversion of the horizontal component of the earth's magnetic field. The coils were activated and deactivated at 5 min intervals during the 1 hour exposure period. In both mice and rats, the levels of serotonin in the pineal were markedly increased by the exposure. In rats, an increase of pineal 5-hydroxyindole acetic acid and a decrease of the activity of the pineal enzyme serotonin-N-acetyltransferase also was observed. However, pineal and serum melatonin levels were not altered. The results indicate that the metabolism of serotonin in the pineal is quickly affected by the exposure of animals to a magnetic field.

  1. Glia-pinealocyte network: the paracrine modulation of melatonin synthesis by tumor necrosis factor (TNF).

    PubMed

    da Silveira Cruz-Machado, Sanseray; Pinato, Luciana; Tamura, Eduardo Koji; Carvalho-Sousa, Cláudia Emanuele; Markus, Regina P

    2012-01-01

    The pineal gland, a circumventricular organ, plays an integrative role in defense responses. The injury-induced suppression of the pineal gland hormone, melatonin, which is triggered by darkness, allows the mounting of innate immune responses. We have previously shown that cultured pineal glands, which express toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1), produce TNF when challenged with lipopolysaccharide (LPS). Here our aim was to evaluate which cells present in the pineal gland, astrocytes, microglia or pinealocytes produced TNF, in order to understand the interaction between pineal activity, melatonin production and immune function. Cultured pineal glands or pinealocytes were stimulated with LPS. TNF content was measured using an enzyme-linked immunosorbent assay. TLR4 and TNFR1 expression were analyzed by confocal microscopy. Microglial morphology was analyzed by immunohistochemistry. In the present study, we show that although the main cell types of the pineal gland (pinealocytes, astrocytes and microglia) express TLR4, the production of TNF induced by LPS is mediated by microglia. This effect is due to activation of the nuclear factor kappa B (NF-kB) pathway. In addition, we observed that LPS activates microglia and modulates the expression of TNFR1 in pinealocytes. As TNF has been shown to amplify and prolong inflammatory responses, its production by pineal microglia suggests a glia-pinealocyte network that regulates melatonin output. The current study demonstrates the molecular and cellular basis for understanding how melatonin synthesis is regulated during an innate immune response, thus our results reinforce the role of the pineal gland as sensor of immune status.

  2. High membrane permeability for melatonin.

    PubMed

    Yu, Haijie; Dickson, Eamonn J; Jung, Seung-Ryoung; Koh, Duk-Su; Hille, Bertil

    2016-01-01

    The pineal gland, an endocrine organ in the brain, synthesizes and secretes the circulating night hormone melatonin throughout the night. The literature states that this hormone is secreted by simple diffusion across the pinealocyte plasma membrane, but a direct quantitative measurement of membrane permeability has not been made. Experiments were designed to compare the cell membrane permeability to three indoleamines: melatonin and its precursors N-acetylserotonin (NAS) and serotonin (5-HT). The three experimental approaches were (1) to measure the concentration of effluxing indoleamines amperometrically in the bath while cells were being dialyzed internally by a patch pipette, (2) to measure the rise of intracellular indoleamine fluorescence as the compound was perfused in the bath, and (3) to measure the rate of quenching of intracellular fura-2 dye fluorescence as indoleamines were perfused in the bath. These measures showed that permeabilities of melatonin and NAS are high (both are uncharged molecules), whereas that for 5-HT (mostly charged) is much lower. Comparisons were made with predictions of solubility-diffusion theory and compounds of known permeability, and a diffusion model was made to simulate all of the measurements. In short, extracellular melatonin equilibrates with the cytoplasm in 3.5 s, has a membrane permeability of ∼1.7 µm/s, and could not be retained in secretory vesicles. Thus, it and NAS will be "secreted" from pineal cells by membrane diffusion. Circumstances are suggested when 5-HT and possibly catecholamines may also appear in the extracellular space passively by membrane diffusion. PMID:26712850

  3. High membrane permeability for melatonin

    PubMed Central

    Yu, Haijie; Dickson, Eamonn J.; Jung, Seung-Ryoung; Koh, Duk-Su

    2016-01-01

    The pineal gland, an endocrine organ in the brain, synthesizes and secretes the circulating night hormone melatonin throughout the night. The literature states that this hormone is secreted by simple diffusion across the pinealocyte plasma membrane, but a direct quantitative measurement of membrane permeability has not been made. Experiments were designed to compare the cell membrane permeability to three indoleamines: melatonin and its precursors N-acetylserotonin (NAS) and serotonin (5-HT). The three experimental approaches were (1) to measure the concentration of effluxing indoleamines amperometrically in the bath while cells were being dialyzed internally by a patch pipette, (2) to measure the rise of intracellular indoleamine fluorescence as the compound was perfused in the bath, and (3) to measure the rate of quenching of intracellular fura-2 dye fluorescence as indoleamines were perfused in the bath. These measures showed that permeabilities of melatonin and NAS are high (both are uncharged molecules), whereas that for 5-HT (mostly charged) is much lower. Comparisons were made with predictions of solubility-diffusion theory and compounds of known permeability, and a diffusion model was made to simulate all of the measurements. In short, extracellular melatonin equilibrates with the cytoplasm in 3.5 s, has a membrane permeability of ∼1.7 µm/s, and could not be retained in secretory vesicles. Thus, it and NAS will be “secreted” from pineal cells by membrane diffusion. Circumstances are suggested when 5-HT and possibly catecholamines may also appear in the extracellular space passively by membrane diffusion. PMID:26712850

  4. Renal melatonin excretion in sheep is enhanced by water diuresis.

    PubMed

    Valtonen, M; Laitinen, J T; Eriksson, L

    1993-09-01

    Diurnal variation in blood melatonin levels and renal melatonin excretion was monitored in five ewes by blood sampling and quantitative urine collection at 2-h intervals. A typical secretory pattern of melatonin was seen both in blood and urine levels and in the renal excretion of melatonin. Serum melatonin levels increased from daytime values of approximately 200 pmol/l to a mean of 800 pmol/l during darkness. Urine flow rate and urine osmolality did not show any clear diurnal rhythm. To examine whether urine flow rate affects renal melatonin excretion at night, urine was collected in three consecutive 30-min fractions, and blood was sampled in the middle of each urine collection period when the sheep were in normal water balance or after hydration. Hydration increased urine flow rate over sixfold and decreased urine osmolality well below plasma osmolality. Glomerular filtration rate, measured as creatinine clearance, did not change. Serum melatonin concentrations did not differ between hydrated and non-hydrated sheep. However, urinary melatonin excretion was 1.1 +/- 0.3 (S.E.M.) pmol/min at midnight in normal water balance, and significantly higher (2.6 +/- 0.4 pmol/min) in the hydrated state. In this study, the validity of urinary melatonin determinations as an indicator of pineal function was confirmed in normal water balance. In addition, our results suggest that a high tubular fluid load during diuresis increases urinary melatonin excretion because of decreased tubular reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Neurobiology, Pathophysiology, and Treatment of Melatonin Deficiency and Dysfunction

    PubMed Central

    Hardeland, Rüdiger

    2012-01-01

    Melatonin is a highly pleiotropic signaling molecule, which is released as a hormone of the pineal gland predominantly during night. Melatonin secretion decreases during aging. Reduced melatonin levels are also observed in various diseases, such as types of dementia, some mood disorders, severe pain, cancer, and diabetes type 2. Melatonin dysfunction is frequently related to deviations in amplitudes, phasing, and coupling of circadian rhythms. Gene polymorphisms of melatonin receptors and circadian oscillator proteins bear risks for several of the diseases mentioned. A common symptom of insufficient melatonin signaling is sleep disturbances. It is necessary to distinguish between symptoms that are curable by short melatonergic actions and others that require extended actions during night. Melatonin immediate release is already effective, at moderate doses, for reducing difficulties of falling asleep or improving symptoms associated with poorly coupled circadian rhythms, including seasonal affective and bipolar disorders. For purposes of a replacement therapy based on longer-lasting melatonergic actions, melatonin prolonged release and synthetic agonists have been developed. Therapies with melatonin or synthetic melatonergic drugs have to consider that these agents do not only act on the SCN, but also on numerous organs and cells in which melatonin receptors are also expressed. PMID:22629173

  6. Circadian melatonin production develops faster in birds than in mammals.

    PubMed

    Zeman, Michal; Herichová, Iveta

    2011-05-15

    The development of circadian rhythmicity of melatonin biosynthesis in the pineal gland starts during embryonic period in birds while it is delayed to the postnatal life in mammals. Daily rhythms of melatonin in isolated pinealocytes and in intact pineal glands under in vivo conditions were demonstrated during the last third of embryonic development in chick embryos, with higher levels during the dark (D) than during the light (L) phase. In addition to the LD cycle, rhythmic temperature changes with the amplitude of 4.5°C can entrain rhythmic melatonin biosynthesis in chick embryos, with higher concentrations found during the low-temperature phase (33.0 vs 37.5°C). Molecular clockwork starts to operate during the embryonic life in birds in line with the early development of melatonin rhythmicity. Expression of per2 and cry genes is rhythmic at least at day 16 and 18, respectively, and the circadian system operates in a mature-like manner soon after hatching. Rhythmic oscillations are detected earlier in the central oscillator (the pineal gland) than in the peripheral structures, reflecting the synchronization of individual cells which is necessary for detection of the rhythm. The early development of the circadian system in birds reflects an absence of rhythmic maternal melatonin which in mammals synchronizes physiological processes of offspring. Developmental consequences of modified development of circadian system for its stability later in development are not known and should be studied.

  7. 60 YEARS OF NEUROENDOCRINOLOGY: Regulation of mammalian neuroendocrine physiology and rhythms by melatonin.

    PubMed

    Johnston, Jonathan D; Skene, Debra J

    2015-08-01

    The isolation of melatonin was first reported in 1958. Since the demonstration that pineal melatonin synthesis reflects both daily and seasonal time, melatonin has become a key element of chronobiology research. In mammals, pineal melatonin is essential for transducing day-length information into seasonal physiological responses. Due to its lipophilic nature, melatonin is able to cross the placenta and is believed to regulate multiple aspects of perinatal physiology. The endogenous daily melatonin rhythm is also likely to play a role in the maintenance of synchrony between circadian clocks throughout the adult body. Pharmacological doses of melatonin are effective in resetting circadian rhythms if taken at an appropriate time of day, and can acutely regulate factors such as body temperature and alertness, especially when taken during the day. Despite the extensive literature on melatonin physiology, some key questions remain unanswered. In particular, the amplitude of melatonin rhythms has been recently associated with diseases such as type 2 diabetes mellitus but understanding of the physiological significance of melatonin rhythm amplitude remains poorly understood.

  8. Melatonin site and mechanism of action: single or multiple?

    PubMed

    Cardinali, D P; Golombek, D A; Rosenstein, R E; Cutrera, R A; Esquifino, A I

    1997-08-01

    By affecting the entrainment pathways of the biologic clock, melatonin has a major influence on the circadian and seasonal organization of vertebrates. In addition, a number of versatile functions that far transcend melatonin actions on photoperiodic time measurement and circadian entrainment have emerged. Melatonin is a free radical scavenger and antioxidant and it has a significant immunomodulatory activity, being presumably a major factor in an organism's defense toxic agents and invading organisms. Besides affecting specific receptors in cell membranes to exert its effects, the interaction of melatonin with nuclear receptor sites and with intracellular proteins, like calmodulin or tubulin-associated proteins, as well as the direct antioxidant effects of melatonin, may explain many general functions of the pineal hormone. PMID:9379344

  9. Pineal and habenula calcification in schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    Animal data indicate that melatonin secretion is stimulated by the paraventricular nucleus (PVN) of the hypothalamus and that lesions of the PVN mimic the endocrine effects of pinealectomy. Since the PVN lies adjacent to the third ventricle, I propose that periventricular damage, which is found in schizophrenia and may account for the third ventricular dilatation seen on computed tomographic (CT), may disrupt PVN-pineal interactions and ultimately enhance the process of pineal calcification (PC). To investigate this hypothesis, I conducted CT study on the relationship of PC size to third ventricular width (TVW) in 12 chronic schizophrenic patients (mean age: 33.7 years; SD = 7.3). For comparison, I also studied the relationship of PC size to the ventricular brain ratio and prefrontal cortical atrophy. As predicted, there was a significant correlation between PC size and TVW (r pbi = .61, p < .05), whereas PC was unrelated to the control neuroradiological measures. The findings support the hypothesis that periventricular damage may be involved in the process of PC in schizophrenia and may indirectly implicate damage to the PVN in the mechanisms underlying dysfunction of the pineal gland in schizophrenia. In a second study, I investigated the prevalence of habenular calcification (HAC) on CT in a cohort of 23 chronic schizophrenic-patients (mean age: 31.2 years; SD = 5.95). In this sample HAC was present in 20 patients (87%). Since the prevalence of HAC in a control population of similar age is only 15% these data reveal an almost 6-fold higher prevalence of HAC (X2 = 84.01, p < .0001) in chronic schizophrenia as compared to normal controls. The implications of HAC for the pathophysiology of schizophrenia are discussed in light of the central role of the habenula in the regulation of limbic functions.

  10. Pineal and habenula calcification in schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    Animal data indicate that melatonin secretion is stimulated by the paraventricular nucleus (PVN) of the hypothalamus and that lesions of the PVN mimic the endocrine effects of pinealectomy. Since the PVN lies adjacent to the third ventricle, I propose that periventricular damage, which is found in schizophrenia and may account for the third ventricular dilatation seen on computed tomographic (CT), may disrupt PVN-pineal interactions and ultimately enhance the process of pineal calcification (PC). To investigate this hypothesis, I conducted CT study on the relationship of PC size to third ventricular width (TVW) in 12 chronic schizophrenic patients (mean age: 33.7 years; SD = 7.3). For comparison, I also studied the relationship of PC size to the ventricular brain ratio and prefrontal cortical atrophy. As predicted, there was a significant correlation between PC size and TVW (r pbi = .61, p < .05), whereas PC was unrelated to the control neuroradiological measures. The findings support the hypothesis that periventricular damage may be involved in the process of PC in schizophrenia and may indirectly implicate damage to the PVN in the mechanisms underlying dysfunction of the pineal gland in schizophrenia. In a second study, I investigated the prevalence of habenular calcification (HAC) on CT in a cohort of 23 chronic schizophrenic-patients (mean age: 31.2 years; SD = 5.95). In this sample HAC was present in 20 patients (87%). Since the prevalence of HAC in a control population of similar age is only 15% these data reveal an almost 6-fold higher prevalence of HAC (X2 = 84.01, p < .0001) in chronic schizophrenia as compared to normal controls. The implications of HAC for the pathophysiology of schizophrenia are discussed in light of the central role of the habenula in the regulation of limbic functions. PMID:1305634

  11. Pineal physiology in microgravity - Relation to rat gonadal function aboard Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Holley, Daniel C.; Markley, Carol L.; Soliman, Magdi R. I.; Kaddis, Farida; Krasnov, Igor'

    1991-01-01

    Results are reported from an analysis of pineal glands obtained for five male rats flown aboard an orbiting satellite for their melatonin, serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIA), and calcium content. Plasma 5-HT and 5-HIAA were measured. These parameters were compared to indicators of gonadal function: plasma testosterone concentration and spermatogonia development. Plasma melotonin was found to be low at the time of euthanasia and was not different among the experimental groups. Pineal calcium of flight animals was not different from ground controls. Pineal 5-HT and 5-HIAA in the flight group were significantly higher than those in ground controls. These findings suggest a possible increase in pineal 5-HT turnover in flight animals which may result in increased melatonin secretion. It is argued that the alteration of pinal 5-HT turnover and its expected effects on melatonin secretion may partially explain the lower plasma testosterone levels and 4-11 percent fewer spermatogonia cells observed in flight animals.

  12. Formation of melatonin and its isomer during bread dough fermentation and effect of baking.

    PubMed

    Yılmaz, Cemile; Kocadağlı, Tolgahan; Gökmen, Vural

    2014-04-01

    Melatonin is produced mainly by the pineal gland in vertebrates. Also, melatonin and its isomer are found in foods. Investigating the formation of melatonin and its isomer is of importance during bread dough fermentation and its degradation during baking since bread is widely consumed in high amounts. Formation of melatonin was not significant during dough fermentation. The melatonin isomer content of nonfermented dough was found to be 4.02 ng/g and increased up to 16.71 ng/g during fermentation. Lower amounts of isomer in crumb and crust than dough showed that the thermal process caused a remarkable degree of degradation in melatonin isomer. At the end of the 180 min fermentation Trp decreased by 58%. The results revealed for the first time the formation of a melatonin isomer in bread dough during yeast fermentation.

  13. Pineal calcification in relation to menopause in schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    I have suggested that critical changes in melatonin secretion, as mediated by the pineal gland, may exert a crucial role in the onset and pathogenesis of schizophrenia. Since pineal calcification (PC) is thought to reflect the metabolic and secretory activity of the gland, I investigated in 29 randomly selected chronic institutionalized female schizophrenic patients the association of PC on CT scan with premenopausal (prior to age 40) versus menopausal (ages 40-55) onset of illness. The premenopausal patients were found to show a significantly higher prevalence of PC than the menopausal patients (55.5% vs. 18.1%; X2 = 3.93, df = 1, p < .05). Since PC was unrelated to historical, demographic, and treatment variables, these findings highlight the importance of the pineal gland for the timing of the onset of schizophrenia, particularly in relation to the female reproductive state. The results carry theoretical implications on the pathogenesis of schizophrenia and suggest that the pineal gland may exert a protective effect against its onset. PMID:1305625

  14. Melatonin modulates secretion of growth hormone and prolactin by trout pituitary glands and cells in culture.

    PubMed

    Falcón, J; Besseau, L; Fazzari, D; Attia, J; Gaildrat, P; Beauchaud, M; Boeuf, G

    2003-10-01

    In Teleost fish, development, growth, and reproduction are influenced by the daily and seasonal variations of photoperiod and temperature. Early in vivo studies indicated the pineal gland mediates the effects of these external factors, most probably through the rhythmic production of melatonin. The present investigation was aimed at determining whether melatonin acts directly on the pituitary to control GH and prolactin (PRL) secretion in rainbow trout. We show that 2-[125I]-iodomelatonin, a melatonin analog, binds selectively to membrane preparations and tissue sections from trout pituitaries. The affinity was within the range of that found for the binding to brain microsomal preparations, but the number of binding sites was 20-fold less than in the brain. In culture, melatonin inhibited pituitary cAMP accumulation induced by forskolin, the adenyl cyclase stimulator. Forskolin also induced an increase in GH release, which was reduced in the presence of picomolar concentrations of melatonin. At higher concentrations, the effects of melatonin became stimulatory. In the absence of forskolin, melatonin induced a dose-dependent increase in GH release, and a dose-dependent decrease in PRL release. Melatonin effects were abolished upon addition of luzindole, a melatonin antagonist. Our results provide the first evidence that melatonin modulates GH and PRL secretion in Teleost fish pituitary. Melatonin effects on GH have never been reported in any vertebrate before. The effects result from a direct action of melatonin on pituitary cells. The complexity of the observed responses suggests several types of melatonin receptors might be involved.

  15. Melatonin, energy metabolism, and obesity: a review.

    PubMed

    Cipolla-Neto, J; Amaral, F G; Afeche, S C; Tan, D X; Reiter, R J

    2014-05-01

    Melatonin is an old and ubiquitous molecule in nature showing multiple mechanisms of action and functions in practically every living organism. In mammals, pineal melatonin functions as a hormone and a chronobiotic, playing a major role in the regulation of the circadian temporal internal order. The anti-obesogen and the weight-reducing effects of melatonin depend on several mechanisms and actions. Experimental evidence demonstrates that melatonin is necessary for the proper synthesis, secretion, and action of insulin. Melatonin acts by regulating GLUT4 expression and/or triggering, via its G-protein-coupled membrane receptors, the phosphorylation of the insulin receptor and its intracellular substrates mobilizing the insulin-signaling pathway. Melatonin is a powerful chronobiotic being responsible, in part, by the daily distribution of metabolic processes so that the activity/feeding phase of the day is associated with high insulin sensitivity, and the rest/fasting is synchronized to the insulin-resistant metabolic phase of the day. Furthermore, melatonin is responsible for the establishment of an adequate energy balance mainly by regulating energy flow to and from the stores and directly regulating the energy expenditure through the activation of brown adipose tissue and participating in the browning process of white adipose tissue. The reduction in melatonin production, as during aging, shift-work or illuminated environments during the night, induces insulin resistance, glucose intolerance, sleep disturbance, and metabolic circadian disorganization characterizing a state of chronodisruption leading to obesity. The available evidence supports the suggestion that melatonin replacement therapy might contribute to restore a more healthy state of the organism.

  16. Melatonin for the treatment of irritable bowel syndrome.

    PubMed

    Siah, Kewin Tien Ho; Wong, Reuben Kong Min; Ho, Khek Yu

    2014-03-14

    Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain or discomfort, in combination with disturbed bowel habits in the absence of identifiable organic cause. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland and also large number by enterochromaffin cells of the digestive mucosa. Melatonin plays an important part in gastrointestinal physiology which includes regulation of gastrointestinal motility, local anti-inflammatory reaction as well as moderation of visceral sensation. Melatonin is commonly given orally. It is categorized by the United States Food and Drug Administration as a dietary supplement. Melatonin treatment has an extremely wide margin of safety though it may cause minor adverse effects, such as headache, rash and nightmares. Melatonin was touted as a potential effective candidate for IBS treatment. Putative role of melatonin in IBS treatment include analgesic effects, regulator of gastrointestinal motility and sensation to sleep promoter. Placebo-controlled studies in melatonin suffered from heterogeneity in methodology. Most studies utilized 3 mg at bedtime as the standard dose of trial. However, all studies had consistently showed improvement in abdominal pain, some showed improvement in quality of life of IBS patients. Melatonin is a relatively safe drug that possesses potential in treating IBS. Future studies should focus on melatonin effect on gut mobility as well as its central nervous system effect to elucidate its role in IBS patients.

  17. Melatonin for the treatment of irritable bowel syndrome.

    PubMed

    Siah, Kewin Tien Ho; Wong, Reuben Kong Min; Ho, Khek Yu

    2014-03-14

    Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain or discomfort, in combination with disturbed bowel habits in the absence of identifiable organic cause. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland and also large number by enterochromaffin cells of the digestive mucosa. Melatonin plays an important part in gastrointestinal physiology which includes regulation of gastrointestinal motility, local anti-inflammatory reaction as well as moderation of visceral sensation. Melatonin is commonly given orally. It is categorized by the United States Food and Drug Administration as a dietary supplement. Melatonin treatment has an extremely wide margin of safety though it may cause minor adverse effects, such as headache, rash and nightmares. Melatonin was touted as a potential effective candidate for IBS treatment. Putative role of melatonin in IBS treatment include analgesic effects, regulator of gastrointestinal motility and sensation to sleep promoter. Placebo-controlled studies in melatonin suffered from heterogeneity in methodology. Most studies utilized 3 mg at bedtime as the standard dose of trial. However, all studies had consistently showed improvement in abdominal pain, some showed improvement in quality of life of IBS patients. Melatonin is a relatively safe drug that possesses potential in treating IBS. Future studies should focus on melatonin effect on gut mobility as well as its central nervous system effect to elucidate its role in IBS patients. PMID:24627586

  18. The contribution of the pineal gland on daily rhythms and masking in diurnal grass rats, Arvicanthis niloticus.

    PubMed

    Shuboni, Dorela D; Agha, Amna A; Groves, Thomas K H; Gall, Andrew J

    2016-07-01

    Melatonin is a hormone rhythmically secreted at night by the pineal gland in vertebrates. In diurnal mammals, melatonin is present during the inactive phase of the rest/activity cycle, and in primates it directly facilitates sleep and decreases body temperature. However, the role of the pineal gland for the promotion of sleep at night has not yet been studied in non-primate diurnal mammalian species. Here, the authors directly examined the hypothesis that the pineal gland contributes to diurnality in Nile grass rats by decreasing activity and increasing sleep at night, and that this could occur via effects on circadian mechanisms or masking, or both. Removing the pineal gland had no effect on the hourly distribution of activity across a 12:12 light-dark (LD) cycle or on the patterns of sleep-like behavior at night. Masking effects of light at night on activity were also not significantly different in pinealectomized and control grass rats, as 1h pulses of light stimulated increases in activity of sham and pinealectomized animals to a similar extent. In addition, the circadian regulation of activity was unaffected by the surgical condition of the animals. Our results suggest that the pineal gland does not contribute to diurnality in the grass rat, thus highlighting the complexity of temporal niche transitions. The current data raise interesting questions about how and why genetic and neural mechanisms linking melatonin to sleep regulatory systems might vary among mammals that reached a diurnal niche via parallel and independent pathways.

  19. Vesicular Glutamate Transporter 2 Expression in the Rat Pineal Gland: Detailed Analysis of Expression Pattern and Regulatory Mechanism

    NASA Astrophysics Data System (ADS)

    Yoshida, Sachine; Hisano, Setsuji

    Melatonin, a hormone secreted by the pineal gland, is closely related physiologically to circadian rhythm, sleep and reproduction, and also psychiatrically to mood disorders in humans. Under circadian control, melatonin secretion is modulated via nocturnal autonomic (adrenergic) stimulation to the gland, which expresses vesicular glutamate transporter (VGLUT) 1, VGLUT2 and a VGLUT1 splice variant (VGLUT1v), glutamatergic markers. Expression of VGLUT2 gene and protein in the intact gland has been reported to exhibit a rhythmic change during a day. To study VGLUT2 expression is under adrenergic control, we here performed an in vitro experiment using dispersed pineal cells of rats. Stimulation of either β-adrenergic receptor or cAMP production to the pineal cells was shown to increase mRNA level of VGLUT2, but not VGLUT1 and VGLUT1v. Because an ability of glutamate to inhibit melatonin production was previously reported in the cultured gland, it is likely that pineal VGLUT2 transports glutamate engaged in the inhibition of melatonin production.

  20. EXTIRPATION OF THE PINEAL BODY

    PubMed Central

    Dandy, Walter E.

    1915-01-01

    1. Following the removal of the pineal I have observed no sexual precocity or indolence, no adiposity or emaciation, no somatic or mental precocity or retardation. 2. Our experiments seem to have yielded nothing to sustain the view that the pineal gland has an active endocrine function of importance either in the very young or adult dogs. 3. The pineal is apparently not essential to life and seems to have no influence upon the animal's well being. PMID:19867913

  1. Renal neurohormonal regulation in heart failure decompensation.

    PubMed

    Jönsson, Sofia; Agic, Mediha Becirovic; Narfström, Fredrik; Melville, Jacqueline M; Hultström, Michael

    2014-09-01

    Decompensation in heart failure occurs when the heart fails to balance venous return with cardiac output, leading to fluid congestion and contributing to mortality. Decompensated heart failure can cause acute kidney injury (AKI), which further increases mortality. Heart failure activates signaling systems that are deleterious to kidneys such as renal sympathetic nerve activity (RSNA), renin-angiotensin-aldosterone system, and vasopressin secretion. All three reduce renal blood flow (RBF) and increase tubular sodium reabsorption, which may increase renal oxygen consumption causing AKI through renal tissue hypoxia. Vasopressin contributes to venous congestion through aquaporin-mediated water retention. Additional water retention may be mediated through vasopressin-induced medullary urea transport and hyaluronan but needs further study. In addition, there are several systems that could protect the kidneys and reduce fluid retention such as natriuretic peptides, prostaglandins, and nitric oxide. However, the effect of natriuretic peptides and nitric oxide are blunted in decompensation, partly due to oxidative stress. This review considers how neurohormonal signaling in heart failure drives fluid retention by the kidneys and thus exacerbates decompensation. It further identifies areas where there is limited data, such as signaling systems 20-HETE, purines, endothelin, the role of renal water retention mechanisms for congestion, and renal hypoxia in AKI during heart failure.

  2. Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

    PubMed Central

    Peschke, Elmar; Bähr, Ina; Mühlbauer, Eckhard

    2013-01-01

    The pineal hormone melatonin exerts its influence in the periphery through activation of two specific trans-membrane receptors: MT1 and MT2. Both isoforms are expressed in the islet of Langerhans and are involved in the modulation of insulin secretion from β-cells and in glucagon secretion from α-cells. De-synchrony of receptor signaling may lead to the development of type 2 diabetes. This notion has recently been supported by genome-wide association studies identifying particularly the MT2 as a risk factor for this rapidly spreading metabolic disturbance. Since melatonin is secreted in a clearly diurnal fashion, it is safe to assume that it also has a diurnal impact on the blood-glucose-regulating function of the islet. This factor has hitherto been underestimated; the disruption of diurnal signaling within the islet may be one of the most important mechanisms leading to metabolic disturbances. The study of melatonin–insulin interactions in diabetic rat models has revealed an inverse relationship: an increase in melatonin levels leads to a down-regulation of insulin secretion and vice versa. Elucidation of the possible inverse interrelationship in man may open new avenues in the therapy of diabetes. PMID:23535335

  3. Maternal stress induces adult reduced REM sleep and melatonin level.

    PubMed

    Feng, Pingfu; Hu, Yufen; Vurbic, Drina; Guo, Yang

    2012-05-01

    We have previously reported that neonatal maternal deprivation (MD) resulted in a decrease of total sleep and an increase of orexin A in adult rats. Now, we characterized features of sleep, activity, and melatonin levels in rats neonatally treated with MD and control (MC) procedures. Adult male Sprague-Dawley rats were treated with either MD or MC procedures for 10 days starting at postnatal day 4. At 3 months of age, sleep was recorded for 48 h in one set of MD and MC rats, while another set of MD and MC rats was measured for locomotor activity (under LD = 12:12). Melatonin levels in the blood, pineal gland, and hypothalamus were measured as well as clock protein level in the hypothalamus. Compared to the MC rats, REM sleep in the MD rats was significantly reduced in the light periods but not in the dark periods. Both quiet wake and total wake in the MD rats were significantly increased during the light period compared to the MC rats. The weight of the pineal gland of the MD rats was significantly smaller than in MC rats. Melatonin levels of the MD group were significantly reduced in the pineal gland and hypothalamus compared to the MC group. No significant difference was identified between groups in the expression of the clock protein in the hypothalamus. Neonatal MD resulted in reduced REM sleep and melatonin levels, without changes of circadian cycle of locomotor activity and levels of clock protein.

  4. TransRapid TR-07 maglev-spectrum magnetic field effects on daily pineal indoleamine metabolic rhythms in rodents

    SciTech Connect

    Groh, K.R.

    1993-01-01

    This study examined the effects on pineal function of magnetic field (MF) exposures (ac and dc components) similar to those produced by the TransRapid TR-07 and other electromagnetic maglev systems (EMS). Rats were entrained to a light-dark cycle and then exposed to a continuous, or to an inverted, intermittent (on = 45 s, off = 15 s, induced current = 267 G/s) simulated multifrequency ac and dc magnetic field (MF) at 1 or 7 times the TR-07 maglev vehicle MF intensity for 2 hr. Other groups of rats were exposed to only the ac or the dc-component of the maglev MF. For comparison, one group was exposed to an inverted, intermittent 60-Hz MF. Each group was compared to an unexposed group of rats for changes in pineal melatonin and serotonin-N-acetyltransferase (NAT). MF exposures at an intensity equivalent to that produced by the TR-07 vehicle had no effect on melatonin or NAT compared with sham-exposed animals under any of the conditions examined. However, 7X TR-07-level continuous 2-h MF exposures significantly depressed pineal NAT by 45%. Pineal melatonin was also depressed 33--43% by a continuous 7X TR-07 MF exposure and 28% by an intermittent 60-Hz 850-mG MF, but the results were not statically significant. This study demonstrates that intermittent, combined ac and dc MFs similar to those produced by the TR-07 EMS maglev vehicle alter the normal circadian rhythm of pineal indoleamine metabolism. The pineal regulatory enzyme NAT was more sensitive to MF exposure than melatonin and may be a more desirable measure of the biological effects of MF exposure.

  5. TransRapid TR-07 maglev-spectrum magnetic field effects on daily pineal indoleamine metabolic rhythms in rodents

    SciTech Connect

    Groh, K.R.

    1993-06-01

    This study examined the effects on pineal function of magnetic field (MF) exposures (ac and dc components) similar to those produced by the TransRapid TR-07 and other electromagnetic maglev systems (EMS). Rats were entrained to a light-dark cycle and then exposed to a continuous, or to an inverted, intermittent (on = 45 s, off = 15 s, induced current = 267 G/s) simulated multifrequency ac and dc magnetic field (MF) at 1 or 7 times the TR-07 maglev vehicle MF intensity for 2 hr. Other groups of rats were exposed to only the ac or the dc-component of the maglev MF. For comparison, one group was exposed to an inverted, intermittent 60-Hz MF. Each group was compared to an unexposed group of rats for changes in pineal melatonin and serotonin-N-acetyltransferase (NAT). MF exposures at an intensity equivalent to that produced by the TR-07 vehicle had no effect on melatonin or NAT compared with sham-exposed animals under any of the conditions examined. However, 7X TR-07-level continuous 2-h MF exposures significantly depressed pineal NAT by 45%. Pineal melatonin was also depressed 33--43% by a continuous 7X TR-07 MF exposure and 28% by an intermittent 60-Hz 850-mG MF, but the results were not statically significant. This study demonstrates that intermittent, combined ac and dc MFs similar to those produced by the TR-07 EMS maglev vehicle alter the normal circadian rhythm of pineal indoleamine metabolism. The pineal regulatory enzyme NAT was more sensitive to MF exposure than melatonin and may be a more desirable measure of the biological effects of MF exposure.

  6. Primary pineal malignant melanoma

    PubMed Central

    Cedeño Diaz, Oderay Mabel; Leal, Roberto García; La Cruz Pelea, Cesar

    2011-01-01

    Primary pineal malignant melanoma is a rare entity, with only thirteen cases reported in the world literature to date. We report a case of a 70-year-old man, who consulted with gait disturbance of six months duration, associated in the last month with dizziness, visual abnormalities and diplopia. No other additional melanocytic lesions were found elsewhere. The magnetic resonance showed a 25 mm expansive mass in the pineal gland that was associated with hydrocephaly, ventricular and transependimary oedema. The lesion was partially excised by a supracerebellar infratentorial approach. The histological examination revealed a melanoma. The patient received radiation therapy, but died of disease 16 weeks later. We herein review the literature on this rare tumour and comment on its clinical, radiological and histopathological features and differential diagnosis. PMID:24765293

  7. The photoreceptive cells of the pineal gland in adult zebrafish (Danio rerio).

    PubMed

    Laurà, Rosaria; Magnoli, Domenico; Zichichi, Rosalia; Guerrera, Maria Cristina; De Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

    2012-03-01

    The zebrafish pineal gland plays a fundamental role in the regulation of the circadian rhythm through the melatonin secretion. The pinealocytes, also called photoreceptive cells, are considered the morphofunctional unit of pineal gland. In literature, the anatomical features, the cellular characteristics, and the pinealocytes morphology of zebrafish pineal gland have not been previously described in detail. Therefore, this study was undertaken to analyze the structure and ultrastructure, as well as the immunohistochemical profile of the zebrafish pineal gland with particular reference to the pinealocytes. Here, we demonstrated, using RT-PCR, immunohistochemistry and transmission electron microscopy, the expression of the mRNA for rhodopsin in the pineal gland of zebrafish, as well as its cellular localization exclusively in the pinealocytes of adult zebrafish. Moreover, the ultrastructural observations demonstrated that the pinealocytes were constituted by an outer segment with numerous lamellar membranes, an inner segment with many mitochondria, and a basal pole with the synapses. Our results taken together demonstrated a central role of zebrafish pinealocytes in the control of pineal gland functions.

  8. Central Interleukin-1β Suppresses the Nocturnal Secretion of Melatonin

    PubMed Central

    Herman, A. P.; Bochenek, J.; Król, K.; Krawczyńska, A.; Antushevich, H.; Pawlina, B.; Herman, A.; Romanowicz, K.; Tomaszewska-Zaremba, D.

    2016-01-01

    In vertebrates, numerous processes occur in a rhythmic manner. The hormonal signal reliably reflecting the environmental light conditions is melatonin. Nocturnal melatonin secretion patterns could be disturbed in pathophysiological states, including inflammation, Alzheimer's disease, and depression. All of these states share common elements in their aetiology, including the overexpression of interleukin- (IL-) 1β in the central nervous system. Therefore, the present study was designed to determine the effect of the central injection of exogenous IL-1β on melatonin release and on the expression of the enzymes of the melatonin biosynthetic pathway in the pineal gland of ewe. It was found that intracerebroventricular injections of IL-1β (50 µg/animal) suppressed (P < 0.05) nocturnal melatonin secretion in sheep regardless of the photoperiod. This may have resulted from decreased (P < 0.05) synthesis of the melatonin intermediate serotonin, which may have resulted, at least partially, from a reduced expression of tryptophan hydroxylase. IL-1β also inhibited (P < 0.05) the expression of the melatonin rhythm enzyme arylalkylamine-N-acetyltransferase and hydroxyindole-O-methyltransferase. However, the ability of IL-1β to affect the expression of these enzymes was dependent upon the photoperiod. Our study may shed new light on the role of central IL-1β in the aetiology of disruptions in melatonin secretion. PMID:27212805

  9. Melatonin Therapy in Patients with Alzheimer’s Disease

    PubMed Central

    Cardinali, Daniel P.; Vigo, Daniel E.; Olivar, Natividad; Vidal, María F.; Brusco, Luis I.

    2014-01-01

    Alzheimer’s disease (AD) is a major health problem and a growing recognition exists that efforts to prevent it must be undertaken by both governmental and non-governmental organizations. In this context, the pineal product, melatonin, has a promising significance because of its chronobiotic/cytoprotective properties potentially useful for a number of aspects of AD. One of the features of advancing age is the gradual decrease in circulating melatonin levels. A limited number of therapeutic trials have indicated that melatonin has a therapeutic value as a neuroprotective drug in the treatment of AD and minimal cognitive impairment (which may evolve to AD). Both in vitro and in vivo, melatonin prevented the neurodegeneration seen in experimental models of AD. For these effects to occur, doses of melatonin about two orders of magnitude higher than those required to affect sleep and circadian rhythmicity are needed. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects, which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50–100 mg/day are urgently needed to assess its therapeutic validity in neurodegenerative disorders such as AD. PMID:26784870

  10. New actions of melatonin and their relevance to biometeorology

    NASA Astrophysics Data System (ADS)

    Hardeland, Rüdiger

    Melatonin is not only produced by the pineal gland, retina and parietal but also by various other tissues and cells from vertebrates, invertebrates, fungi, plants, multicellular algae and by unicells. In plants, many invertebrates and unicells, its concentration often exceeds that found in vertebrate blood by several orders of magnitude. The action of melatonin is highly pleiotropic. It involves firstly, direct effects, via specific binding sites in various peripheral tissues and cells of vertebrates, including immunomodulation; secondly, systemic influences on the cytoskeleton and nitric oxide formation, mediated by calmodulin; and thirdly, antioxidative protection, perhaps also in the context of photoprotection in plants and unicells. In some dinoflagellates, melatonin conveys temperature signals. On the basis of these comparisons, melatonin appears to mediate and modulate influences from several major environmental factors, such as the photoperiod, radiation intensity and temperature.

  11. Effects of illumination on human nocturnal serum melatonin levels and performance

    NASA Technical Reports Server (NTRS)

    Dollins, A. B.; Lynch, H. J.; Wurtman, R. J.; Deng, M. H.; Lieberman, H. R.

    1993-01-01

    In humans, exposure to bright light at night suppresses the normal nocturnal elevation in circulating melatonin. Oral administration of pharmacological doses of melatonin during the day, when melatonin levels are normally minimal, induces fatigue. To examine the relationship between illumination, human pineal function, and behavior, we monitored the overnight serum melatonin profiles and behavioral performance of 24 healthy male subjects. On each of three separate occasions subjects participated in 13.5 h (1630-0800 h) testing sessions. Each subject was assigned to an individually illuminated workstation that was maintained throughout the night at an illumination level of approximately 300, 1500, or 3000 lux. Melatonin levels were significantly diminished by light treatment, F(2, 36) = 12.77, p < 0.001, in a dose-dependent manner. Performance on vigilance, reaction time, and other tasks deteriorated throughout the night, consistent with known circadian variations in these parameters, but independent of ambient light intensity and circulating melatonin levels.

  12. Effects of melatonin on cardiovascular diseases: progress in the past year

    PubMed Central

    Sun, Hang; Gusdon, Aaron M.; Qu, Shen

    2016-01-01

    Purpose of review Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland. Numerous studies have suggested that melatonin plays an important role in various cardiovascular diseases. In this article, recent progress regarding melatonin's effects on cardiovascular diseases is reviewed. Recent findings In the past year, studies have focused on the mechanism of protection of melatonin on cardiovascular diseases, including myocardial ischemia-reperfusion injury, myocardial hypoxia-reoxygenation injury, pulmonary hypertension, hypertension, atherosclerosis, valvular heart diseases, and other cardiovascular diseases. Summary Studies have demonstrated that melatonin has significant effects on ischemia-reperfusion injury, myocardial chronic intermittent hypoxia injury, pulmonary hypertension, hypertension, valvular heart diseases, vascular diseases, and lipid metabolism. As an inexpensive and well tolerated drug, melatonin may be a new therapeutic option for cardiovascular disease. PMID:27075419

  13. Potential Relevance of Melatonin Against Some Infectious Agents: A Review and Assessment of Recent Research.

    PubMed

    Elmahallawy, Ehab Kotb; Luque, Javier Ortega; Aloweidi, Abdelkarim Saleh; Gutiérrez-Fernández, José; Sampedro-Martínez, Antonio; Rodriguez-Granger, Javier; Kaki, Abdullah; Agil, Ahmad

    2015-01-01

    Melatonin, a tryptophan-derived neurohormone found in animals, plants, and microbes, participates in various biological and physiological functions. Among other properties, numerous in vitro or in vivo studies have reported its therapeutic potential against many parasites, bacteria and viruses. In this concern, melatonin was found to be effective against many parasites such as Plasmodium, Toxoplasma gondii, and Trypansoma cruzi, via various mechanisms such as modulation of calcium level and/or host immune system. Likewise, a recent investigation has reported in vitro activity of melatonin against Leishmania infantum promastigotes which is the causative agent of fascinating visceral Leishmaniasis. This review was initially undertaken to summarize some facts about certain physiological and therapeutic effects of melatonin. It also reviews the effects and action mechanisms of melatonin in bacterial and viral infection besides biology of different parasites which may provide a promising strategy for control of many diseases of public health importance.

  14. Prenatal melatonin and its interaction with tachykinins in the hypothalamic-pituitary-gonadal axis.

    PubMed

    Díaz López, B; Debeljuk, L

    2007-01-01

    The pineal gland, through its hormone melatonin, influences the function of the hypothalamic-pituitary-gonadal axis. Tachykinins are bioactive peptides whose presence has been demonstrated in the pineal gland, hypothalamus, anterior pituitary gland and the gonads, in addition to other central and peripheral structures. Tachykinins have been demonstrated to influence the function of the hypothalamic-pituitary-gonadal axis, acting as paracrine factors at each of these levels. In the present review, we examine the available evidence supporting a role for melatonin in the regulation of reproductive functions, the possible role of tachykinins in pineal function and the possible interactions between melatonin and tachykinins in the hypothalamic-pituitary-gonadal axis. Evidence is presented showing that melatonin, given to pregnant rats, influences the developmental pattern of tachykinins in the hypothalamus and the anterior pituitary gland of the offspring during postnatal life. In the gonads, the effects of melatonin on the tachykinin developmental pattern were rather modest. In particular, in the present review, we have included a summary of our own work performed in the past few years on the effect of melatonin on tachykinin levels in the hypothalamic-pituitary-gonadal axis.

  15. Testicular response to melatonin or suprachiasmatic nuclei ablation in the spotted skunk.

    PubMed

    Berria, M; DeSantis, M; Mead, R A

    1990-07-01

    Testes of the Western spotted skunk enlarge and regress seasonally. The pineal hormone, melatonin, may be important in timing this seasonal reproductive activity. Likewise, the suprachiasmatic nuclei (SCN) have been implicated as possible neural regulators of pineal and reproductive events. These experiments were conducted to determine whether ablation of the SCN or constant administration of melatonin alters timing of the seasonal pattern of testicular regression and recrudescence. Male skunks (n = 24) were treated as follows: six received two empty Silastic capsules, six received two melatonin-filled Silastic capsules, six received sham lesions to the SCN, and six received lesions to the SCN (SCNx). All skunks were exposed to a natural photoperiod and had regressed testes at the onset of the experiment. Four of six males from the SCNx group had an average of 94 +/- 11.3% of these nuclei destroyed. Sham SCNx, animals with less than 40% of the SCN ablated, and males with empty capsules did not have fully enlarged testes until October. SCNx and melatonin-treated skunks exhibited a hastening of testicular recrudescence with maximal testis size being reached in June. Skunks with lesions to the SCN maintained enlarged testes for 5 months while all other groups exhibited rapid regression after attaining maximal testis size. Testicular regression occurred from July through October in animals receiving continuous melatonin, while controls exhibited recrudescence during this same period. Our data suggest that the SCN, melatonin, and thus the pineal gland, play a role in regulating the seasonal testicular cycle of the spotted skunk.

  16. Melatonin and male reproductive health: relevance of darkness and antioxidant properties.

    PubMed

    Rocha, C S; Rato, L; Martins, A D; Alves, M G; Oliveira, P F

    2015-01-01

    The pineal hormone melatonin controls several physiological functions that reach far beyond the regulation of the circadian rhythm. Moreover, it can be produced in extra-pineal organs such as reproductive organs. The role of melatonin in the mammalian seasonal and circadian rhythm is well known. Nevertheless, its overall effect in male reproductive physiology remains largely unknown. Melatonin is a very powerful endogenous antioxidant that can also be exogenously taken safely. Interestingly, its antioxidant properties have been consistently reported to improve the male reproductive dysfunctions associated with pathological conditions and also with the exposure to toxicants. Nevertheless, the exact molecular mechanisms by which melatonin exerts its action in the male reproductive system remain a matter of debate. Herein, we propose to present an up-to-date overview of the melatonin effects in the male reproductive health and debate future directions to disclose possible sites of melatonin action in male reproductive system. We will discuss not only the role of melatonin during darkness and sleep but also the importance of the antioxidant properties of this hormone to male fertility. Since melatonin readily crosses the physiological barriers, such as the blood-testis barrier, and has a very low toxicity, it appears as an excellent candidate in the prevention and/or treatment of the multiple male reproductive dysfunctions associated with various pathologies.

  17. Protective effects of melatonin on lipopolysaccharide-induced mastitis in mice.

    PubMed

    Shao, Guoxi; Tian, Yinggang; Wang, Haiyu; Liu, Fangning; Xie, Guanghong

    2015-12-01

    Melatonin, a secretory product of the pineal gland, has been reported to have antioxidant and anti-inflammatory effects. However, the protective effects of melatonin on lipopolysaccharide (LPS)-induced mastitis have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of melatonin on LPS-induced mastitis both in vivo and in vitro. In vivo, our results showed that melatonin attenuated LPS-induced mammary histopathologic changes and myeloperoxidase (MPO) activity. Melatonin also inhibited LPS-induced inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in mammary tissues. In vitro, melatonin was found to inhibit LPS-induced TNF-α and IL-6 production in mouse mammary epithelial cells. Melatonin also suppressed LPS-induced Toll-like receptor 4 (TLR4) expression and nuclear factor-kappaB (NF-κB) activation in a dose-dependent manner. In addition, melatonin was found to up-regulate the expression of PPAR-γ. Inhibition of PPAR-γ by GW9662 reduced the anti-inflammatory effects of melatonin. In conclusion, we found that melatonin, for the first time, had protective effects on LPS-induced mastitis in mice. The anti-inflammatory mechanism of melatonin was through activating PPAR-γ which subsequently inhibited LPS-induced inflammatory responses.

  18. Protective effects of melatonin on lipopolysaccharide-induced mastitis in mice.

    PubMed

    Shao, Guoxi; Tian, Yinggang; Wang, Haiyu; Liu, Fangning; Xie, Guanghong

    2015-12-01

    Melatonin, a secretory product of the pineal gland, has been reported to have antioxidant and anti-inflammatory effects. However, the protective effects of melatonin on lipopolysaccharide (LPS)-induced mastitis have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of melatonin on LPS-induced mastitis both in vivo and in vitro. In vivo, our results showed that melatonin attenuated LPS-induced mammary histopathologic changes and myeloperoxidase (MPO) activity. Melatonin also inhibited LPS-induced inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in mammary tissues. In vitro, melatonin was found to inhibit LPS-induced TNF-α and IL-6 production in mouse mammary epithelial cells. Melatonin also suppressed LPS-induced Toll-like receptor 4 (TLR4) expression and nuclear factor-kappaB (NF-κB) activation in a dose-dependent manner. In addition, melatonin was found to up-regulate the expression of PPAR-γ. Inhibition of PPAR-γ by GW9662 reduced the anti-inflammatory effects of melatonin. In conclusion, we found that melatonin, for the first time, had protective effects on LPS-induced mastitis in mice. The anti-inflammatory mechanism of melatonin was through activating PPAR-γ which subsequently inhibited LPS-induced inflammatory responses. PMID:26590117

  19. Modulation of Aanat gene transcription in the rat pineal gland.

    PubMed

    Ho, Anthony K; Chik, Constance L

    2010-01-01

    The main function of the rat pineal gland is to transform the circadian rhythm generated in the suprachiasmatic nucleus into a rhythmic signal of circulating melatonin characterized by a large nocturnal increase that closely reflects the duration of night period. This is achieved through the tight coupling between environmental lighting and the expression of arylalkylamine-N-acetyltransferase, the rhythm-controlling enzyme in melatonin synthesis. The initiation of Aanat transcription at night is controlled largely by the norepinephrine-stimulated phosphorylation of cAMP response element-binding protein by protein kinase A. However, to accurately reflect the duration of darkness, additional signaling mechanisms also participate to fine-tune the temporal profile of adrenergic-induced Aanat transcription. Here, we reviewed some of these signaling mechanisms, with emphasis on the more recent findings. These signaling mechanisms can be divided into two groups: those involving modification of constitutively expressed proteins and those requiring synthesis of new proteins. This review highlights the pineal gland as an excellent model system for studying neurotransmitter-regulated rhythmic gene expression.

  20. Posttranslational regulation of TPH1 is responsible for the nightly surge of 5-HT output in the rat pineal gland.

    PubMed

    Huang, Zheping; Liu, Tiecheng; Chattoraj, Asamanja; Ahmed, Samreen; Wang, Michael M; Deng, Jie; Sun, Xing; Borjigin, Jimo

    2008-11-01

    Serotonin (5-hydroxytryptamine, 5-HT), a precursor for melatonin production, is produced abundantly in the pineal gland of all vertebrate animals. The synthesis of 5-HT in the pineal gland is rate limited by tryptophan hydroxylase 1 (TPH1) whose activity displays a twofold increase at night. Earlier studies from our laboratory demonstrate that pineal 5-HT secretion exhibits dynamic circadian rhythms with elevated levels during the early night, and that the increase is controlled by adrenergic signaling at night. In this study, we report that (a) 5-HT total output from the pineal gland and TPH1 protein levels both display diurnal rhythms with a twofold increase at night; (b) stimulation of cAMP signaling elevates 5-HT output in vivo; (c) 5-HT total output and TPH1 protein content in rat pineal gland are both acutely inhibited by light exposure at night. Consistent with these findings, molecular analysis of TPH1 protein revealed that (a) TPH1 is phosphorylated at the serine 58 in vitro and in the night pineal gland; and (b) phosphorylation of TPH1 at this residue is required for cAMP-enhanced TPH1 protein stability. These data support the model that increased nocturnal 5-HT synthesis in the pineal gland is mediated by the phosphorylation of TPH1 at the serine 58, which elevates the TPH1 protein content and activity at night.

  1. Multiple sclerosis: the role of puberty and the pineal gland in its pathogenesis.

    PubMed

    Sandyk, R

    1993-02-01

    Epidemiological studies demonstrate that the incidence of multiple sclerosis (MS) is age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in the mid 20s. It has been suggested that the manifestation of MS is dependent upon having passed through the pubertal period. In the present communication, I propose that critical changes in pineal melatonin secretion, which occur in temporal relationship to the onset of puberty, are intimately related to the timing of onset of the clinical manifestations of MS. Specifically, it is suggested that the fall in melatonin secretion during the prepubertal period, which may disrupt pineal-mediated immunomodulation, may stimulate either the reactivation of the infective agent or increase the susceptibility to infection during the pubertal period. Similarly, the rapid fall in melatonin secretion just prior to delivery may account for the frequent occurrence of relapse in MS patients during the postpartum period. In contrast, pregnancy, which is associated with high melatonin concentrations, is often accompanied by remission of symptoms. Thus, the presence of high melatonin levels may provide a protective effect, while a decline in melatonin secretion may increase the risk for the development and exacerbation of the disease. The melatonin hypothesis of MS may explain other epidemiological and clinical phenomena associated with the disease such as the low incidence of MS in the black African and American populations, the inverse correlation with sun light and geomagnetic field exposure, the occurrence of relapses in relation to seasonal changes and fluctuations in mood, and the association of MS with affective illness and malignant disease. Therapeutically, this hypothesis implies that application of bright light therapy or the use of other major synchronizers of circadian rhythms such as sleep deprivation or application of external weak magnetic fields may be beneficial in the treatment and/or prophylaxis of

  2. Melatonin Anticancer Effects: Review

    PubMed Central

    Di Bella, Giuseppe; Mascia, Fabrizio; Gualano, Luciano; Di Bella, Luigi

    2013-01-01

    Melatonin (N-acetyl-5-methoxytryptamine, MLT), the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate). The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation). All these particular characteristics suggest the use of MLT in oncological diseases. PMID:23348932

  3. [The participation of the dorsal hippocampus in the antianxiety action of melatonin and diazepam].

    PubMed

    Arushanian, E B; Beĭer, E V

    1998-01-01

    The pineal hormone melatonin and the tranquilizer diazepam given in an equal dose (0.1 mg/kg) demonstrated an anxiolytic effect on a model of a conflict situation in rats. Damage to the dorsal hippocampus produced a similar effect and the anxiolytic activity of the drugs under study was removed against this background.

  4. Pain control by melatonin: Physiological and pharmacological effects

    PubMed Central

    Chen, Wei-Wei; Zhang, Xia; Huang, Wen-Juan

    2016-01-01

    Pain and anxiety are the most common neurological responses to many harmful or noxious stimuli and their management clinically is often challenging. Many of the frequently used morphine-based drugs, non-steroid anti-inflammatory drugs and acetaminophen, while efficient for treating pain, lead to patients suffering from several unwanted side effects. Melatonin, produced from the pineal body is a hormone of darkness, is involved in the control of circadian rhythms, and exerts a number of pharmacological effects. Melatonin mediates its actions through MT1/MT2 melatonin receptors on the cell membrane and also through RZR/ROR nuclear orphan receptors. Chronic pain syndromes are often associated with the desynchronization of circadian and biological rhythms, which also cause disturbances in the sleep-wake cycle. Melatonin-mediated analgesic effects seem to involve β-endorphins, GABA receptor, opioid receptors and the nitric oxide-arginine pathway. The effectiveness of melatonin as an analgesic and anxiolytic agent has been demonstrated in various animal models of pain and this led to the use of melatonin clinically in different pathological conditions and also in patients undergoing surgery. Melatonin was found to be effective in many of these cases as an anxiolytic and analgesic agent, indicating its clinical application. PMID:27698681

  5. Pain control by melatonin: Physiological and pharmacological effects

    PubMed Central

    Chen, Wei-Wei; Zhang, Xia; Huang, Wen-Juan

    2016-01-01

    Pain and anxiety are the most common neurological responses to many harmful or noxious stimuli and their management clinically is often challenging. Many of the frequently used morphine-based drugs, non-steroid anti-inflammatory drugs and acetaminophen, while efficient for treating pain, lead to patients suffering from several unwanted side effects. Melatonin, produced from the pineal body is a hormone of darkness, is involved in the control of circadian rhythms, and exerts a number of pharmacological effects. Melatonin mediates its actions through MT1/MT2 melatonin receptors on the cell membrane and also through RZR/ROR nuclear orphan receptors. Chronic pain syndromes are often associated with the desynchronization of circadian and biological rhythms, which also cause disturbances in the sleep-wake cycle. Melatonin-mediated analgesic effects seem to involve β-endorphins, GABA receptor, opioid receptors and the nitric oxide-arginine pathway. The effectiveness of melatonin as an analgesic and anxiolytic agent has been demonstrated in various animal models of pain and this led to the use of melatonin clinically in different pathological conditions and also in patients undergoing surgery. Melatonin was found to be effective in many of these cases as an anxiolytic and analgesic agent, indicating its clinical application.

  6. Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment

    PubMed Central

    Masters, Alina; Pandi-Perumal, Seithikurippu R; Seixas, Azizi; Girardin, Jean-Louis; McFarlane, Samy I.

    2015-01-01

    Melatonin is a hormone secreted by the enigmatic pineal gland in response to darkness, hence the name hormone of darkness. It has generated a great deal of interest as a therapeutic modality for various diseases particularly sleep disorders. This pleiotropic molecule has anti-inflammatory, antioxidant and anticoagulopathic properties in addition to its endothelial protective effects. In this article we discuss melatonin secretion and mechanisms of action as well as therapeutic rationale. We also highlight the potential utility of melatonin in the deadly modern-day Ebola epidemic. PMID:25705578

  7. Melatonin-synthesizing enzymes and melatonin receptor in rat thyroid cells.

    PubMed

    García-Marín, Rocío; de Miguel, Manuel; Fernández-Santos, José María; Carrillo-Vico, Antonio; Utrilla, José Carmelo; Morillo-Bernal, Jesús; Díaz-Parrado, Eduardo; Rodríguez-Prieto, Ismael; Guerrero, Juan Miguel; Martín-Lacave, Inés

    2012-11-01

    Melatonin is an indoleamine with a wide spectrum of biological activities other than transmitting photoperiod information, including antioxidant, oncostatic, anti-aging and immunomodulatory properties. Although melatonin is synthesized mainly in the pineal gland, other tissues have the same capacity. In the present study, we examined whether two key enzymes in melatonin biosynthesis, arylalkylamine Nacetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT) and its receptor MT₁ are expressed in the two endocrine thyroid cells of the rat, follicular cells and C cells. Reverse transcriptase polymerase chain reaction analyses demonstrated that both AANAT and HIOMT mRNAs are expressed in the rat thyroid C-cells, and MT₁ expression has been detected in C cells and follicular cells. Immunofluorescence revealed that AANAT protein is localized in C-cell cytoplasm, and MT₁ protein in both cell populations. These findings demonstrate that the rat thyroid expresses AANAT, HIOMT, and its receptor MT₁, showing that C cells are the main melatonin-synthesizing sites in the thyroid. This local C-cell-secreted melatonin may protect follicular cells from the oxidative stress inherent to the thyroid gland, and could also have paracrine and autocrine functions.

  8. Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives

    PubMed Central

    Tordjman, Sylvie; Najjar, Imen; Bellissant, Eric; Anderson, George M.; Barburoth, Marianne; Cohen, David; Jaafari, Nemat; Schischmanoff, Olivier; Fagard, Rémi; Lagdas, Enas; Kermarrec, Solenn; Ribardiere, Sophie; Botbol, Michel; Fougerou, Claire; Bronsard, Guillaume; Vernay-Leconte, Julie

    2013-01-01

    Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests. PMID:24129182

  9. Beneficial effects of melatonin in a rat model of sporadic Alzheimer's disease.

    PubMed

    Rudnitskaya, Ekaterina A; Maksimova, Kseniya Yi; Muraleva, Natalia A; Logvinov, Sergey V; Yanshole, Lyudmila V; Kolosova, Nataliya G; Stefanova, Natalia A

    2015-06-01

    Melatonin synthesis is disordered in patients with Alzheimer's disease (AD). To determine the role of melatonin in the pathogenesis of AD, suitable animal models are needed. The OXYS rats are an experimental model of accelerated senescence that has also been proposed as a spontaneous rat model of AD-like pathology. In the present study, we demonstrate that disturbances in melatonin secretion occur in OXYS rats at 4 months of age. These disturbances occur simultaneously with manifestation of behavioral abnormalities against the background of neurodegeneration and alterations in hormonal status but before the signs of amyloid-β accumulation. We examined whether oral administration of melatonin could normalize the melatonin secretion and have beneficial effects on OXYS rats before progression to AD-like pathology. The results showed that melatonin treatment restored melatonin secretion in the pineal gland of OXYS rats as well as the serum levels of growth hormone and IGF-1, the level of BDNF in the hippocampus and the healthy state of hippocampal neurons. Additionally, melatonin treatment of OXYS rats prevented an increase in anxiety and the decline of locomotor activity, of exploratory activity, and of reference memory. Thus, melatonin may be involved in AD progression, whereas oral administration of melatonin could be a prophylactic strategy to prevent or slow down the progression of some features of AD pathology.

  10. Pineal Calcification Among Black Patients

    PubMed Central

    Fan, Kuang-Jaw

    1983-01-01

    A postmortem histopathological study was done in 233 pineal glands of black patients. Among them, 70 percent showed microscopic evidence of calcification in the pineal parenchyma. The frequency of calcification increased with age. However, the severity of calcification reached the peak in the 60 to 69 year old age group and then gradually declined. As compared to males, females had slightly higher frequency and reached the peak of severity in younger age groups. When pineal calcification was compared among patients with various malignancies, a higher frequency and more severe calcification were observed in patients with carcinoma of the prostate and the pancreas. A lower frequency and less severe calcification were observed in patients with carcinoma of the breast and the cervix. The results of this study emphasize the important role of sex hormone in genesis of pineal calcification. PMID:6631985

  11. Pineal calcification among black patients.

    PubMed

    Fan, K J

    1983-08-01

    A postmortem histopathological study was done in 233 pineal glands of black patients. Among them, 70 percent showed microscopic evidence of calcification in the pineal parenchyma. The frequency of calcification increased with age. However, the severity of calcification reached the peak in the 60 to 69 year old age group and then gradually declined. As compared to males, females had slightly higher frequency and reached the peak of severity in younger age groups. When pineal calcification was compared among patients with various malignancies, a higher frequency and more severe calcification were observed in patients with carcinoma of the prostate and the pancreas. A lower frequency and less severe calcification were observed in patients with carcinoma of the breast and the cervix. The results of this study emphasize the important role of sex hormone in genesis of pineal calcification.

  12. Lymphopoiesis in the chicken pineal gland

    SciTech Connect

    Cogburn, L.A.; Glick, B.

    1981-10-01

    Pineal lymphoid development was studied in two breeds of chickens from hatching until sexual maturity. No lymphocytes were found in the pineal prior to 9 days of age (da). Lymphocytes migrate through the endothelium of venules into the pineal stroma. Lymphoid tissue reached its maximal accumulation in 32-da pineal glands of both breeds. At this age, the New Hampshire (NH) breed had a larger proportion of lymphoid volume to total pineal volume (32%) than did pineal glands from White Leghorn (WL) chickens (18%).

  13. Comparative histology of pineal calcification.

    PubMed

    Vígh, B; Szél, A; Debreceni, K; Fejér, Z; Manzano e Silva, M J; Vígh-Teichmann, I

    1998-07-01

    The pineal organ (pineal gland, epiphysis cerebri) contains several calcified concretions called "brain sand" or acervuli (corpora arenacea). These concretions are conspicuous with imaging techniques and provide a useful landmark for orientation in the diagnosis of intracranial diseases. Predominantly composed of calcium and magnesium salts, corpora arenacea are numerous in old patients. In smaller number they can be present in children as well. The degree of calcification was associated to various diseases. However, the presence of calcified concretions seems not to reflect a specific pathological state. Corpora arenacea occur not only in the actual pineal tissue but also in the leptomeninges, in the habenular commissure and in the choroid plexus. Studies with the potassium pyroantimonate (PPA) method on the ultrastructural localization of free calcium ions in the human pineal, revealed the presence of calcium alongside the cell membranes, a finding that underlines the importance of membrane functions in the production of calcium deposits. Intrapineal corpora arenacea are characterized by a surface with globular structures. Meningeal acervuli that are present in the arachnoid cover of the organ, differ in structure from intrapineal ones and show a prominent concentric lamination of alternating dark and light lines. The electron-lucent lines contain more calcium than the dark ones. There is a correlation between the age of the subject and the number of layers in the largest acervuli. This suggests that the formation of these layers is connected to circannual changes in the calcium level of the organ. The histological organization of the human pineal is basically the same as that of mammalian experimental animals. Pineal concretions present in mammalian animal species are mainly of the meningeal type. Meningeal cells around acervuli contain active cytoplasmic organelles and exhibit alkaline phosphatase reaction in the rat and mink, an indication of a presumable

  14. Acute increases in night-time plasma melatonin levels following a period of meditation.

    PubMed

    Tooley, G A; Armstrong, S M; Norman, T R; Sali, A

    2000-05-01

    To determine whether a period of meditation could influence melatonin levels, two groups of meditators were tested in a repeated measures design for changes in plasma melatonin levels at midnight. Experienced meditators practising either TM-Sidhi or another internationally well known form of yoga showed significantly higher plasma melatonin levels in the period immediately following meditation compared with the same period at the same time on a control night. It is concluded that meditation, at least in the two forms studied here, can affect plasma melatonin levels. It remains to be determined whether this is achieved through decreased hepatic metabolism of the hormone or via a direct effect on pineal physiology. Either way, facilitation of higher physiological melatonin levels at appropriate times of day might be one avenue through which the claimed health promoting effects of meditation occur.

  15. [Bulimia, bulimia-anorexia and nocturnal secretion of melatonin and cortisol].

    PubMed

    Parienti, V; Kennedy, S H; Brown, G M; Costa, D

    1988-01-01

    The authors compared nocturnal variations of melatonin (MT) and cortisol levels in subjects with bulimia (n = 12), 6 with a normal body weight and 6 with anorexia nervosa, as well as 6 control subjects. The hypothesis, formulated for anorexia nervosa, that a decrease of noradrenergic activity induces a decrease of pineal activity, therefore a decrease of melatonin secretion, was not confirmed by our study. Moreover, in subjects with bulimia in the absence of anorexia nervosa, no significant decrease of nocturnal melatonin secretion was reported. Significant differences were due to cortisol variations when comparing MTmax/Cmin ratios. Melatonin did not add any complementary biological cue for diagnostic assessment for subjects with eating disorder and depression. The results of this study suggest that melatonin does not appear to be a useful biological marker in bulimia.

  16. Multiple sclerosis: the role of the pineal gland in its timing of onset and risk of psychiatric illness.

    PubMed

    Sandyk, R; Awerbuch, G I

    1993-09-01

    The incidence of multiple sclerosis (MS) is age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in the mid 20s. It has been suggested, therefore, that the clinical manifestation of MS is dependent upon having passed the pubertal period. Since pineal melatonin secretion declines from childhood to puberty and as melatonin is an immunomodulator, we have proposed that the dramatic decline in melatonin secretion just prior to the onset of the physical manifestations of puberty may disrupt immune responses resulting in either reactivation of the infective agent or in an increased susceptibility to post-pubertal infection. The fall in melatonin secretion during pre-puberty may also increase the susceptibility of these patients to affective disorder which is associated with lower melatonin secretion and the presence of a phase-advance of their biological rhythms. We predicted, therefore, a higher incidence of affective disorder in patients with pubertal or post-pubertal onset of MS compared to those in whom the disease manifested later. To test this hypothesis, we studied the incidence of affective disorder in relation to age of onset of first neurological symptoms in 31 MS patients, 6 of whom manifested symptoms of MS prior to age 18 (mean = 16.8 years). All patients with pubertal onset MS and only 48% of the control group had an affective disorder. The pubertal onset patients also had a significantly lower nocturnal melatonin levels and a lower incidence of pineal calcification on CT scan. These findings thus support the hypothesis implicating the pineal gland in the timing of onset of MS and in the risk for the development of affective disorder. PMID:8225803

  17. Melatonin and farm animals: endogenous rhythms and exogenous applications.

    PubMed

    Paterson, A M; Foldes, A

    1994-05-01

    further study include: the significance of the abolition of the nocturnal melatonin peak in the sheep by prolonged short day exposure; the increased pineal bloodflow in sheep bred to produce high wool yields; the presence of high daytime melatonin levels immediately prior to the rut in the fallow buck; and the low amplitude of the rhythm in the domestic pig. PMID:7807370

  18. A 15-minute light pulse during darkness prevents the antigonadotrophic action of afternoon melatonin injections in male hamsters

    NASA Astrophysics Data System (ADS)

    Reiter, R. J.; Hurlbut, E. C.; King, T. S.; Richardson, B. A.; Vaughan, M. K.; Kosub, K. Y.

    1982-12-01

    When adult male Syrian hamsters were maintained under 14 h light and 10 h darkness daily (lights on from 0600-2000 h), peak pineal melatonin levels (705 pg/gland) were attained at 0500 h. When the dark phase of the light:dark cycle was interrupted with a 15 min pulse of light from 2300 2315 h (3 h after lights out), the highest melatonin levels achieved was roughly 400 pg/gland. Finally, if the 15 min pulse of light was given at 0200 0215 h (6 h after lights out) the nocturnal rise in pineal melatonin was completely abolished. Having made these observations, a second experiment was designed to determine the ability of afternoon melatonin injections to inhibit reproduction in hamsters kept under an uninterrupted 14∶10 cycle or under the same lighting regimen where the dark phase was interrupted with a 15 min pulse of light (0200 0215 h). In the uninterrupted light:dark schedule the daily afternoon injection of 25 μg melatonin caused the testes and the accessory sex organs to atrophy within 11 weeks. Conversely, if the dark phase was interrupted with light between 0200 0215 h, afternoon melatonin injections were incapable of inhibiting the growth of the reproductive organs. The findings suggest that exogenously administered melatonin normally synergizes with endogenously produced melatonin to cause gonadal involution in hamsters.

  19. A role for melatonin in maintaining the pro- and anti-inflammatory balance by influencing leukocyte migration and apoptosis in carp.

    PubMed

    Kepka, Magdalena; Szwejser, Ewa; Pijanowski, Lukasz; Verburg-van Kemenade, B M Lidy; Chadzinska, Magdalena

    2015-11-01

    Melatonin is responsible for the synchronization of many physiological processes, including the immune response. Here we focus on the expression of melatonin MT1 receptors in/on leukocytes, and on the effects of melatonin administration on the inflammatory processes of carp. For the first time, we showed that fish leukocytes express MT1 receptors, implicating direct responsiveness to melatonin stimulation. Moreover, both in vitro and in vivo, melatonin modulated the immune response. The most potent effects of melatonin concerned the regulation of leukocyte migration. Melatonin reduced chemotaxis of leukocytes towards CXC chemokines in vitro. In vivo, during zymosan induced peritonitis, i.p. administration of melatonin reduced the number of neutrophils. This correlated with a melatonin-induced decrease of gene expression of the CXCa chemokine. Moreover, melatonin induced a decrease of the respiratory burst in inflammatory leukocytes. Although these data do suggest a potent anti-inflammatory function for this hormone, melatonin-induced inhibition of leukocyte apoptosis clearly indicates towards a dual function. These results show that also in carp, melatonin performs a pleiotropic and extra-pineal function that is important in maintaining the delicate pro- and anti-inflammatory balance during infection. They furthermore demonstrate that neuroendocrine-immune interaction via melatonin is evolutionary conserved.

  20. Scavenging effect of melatonin on hydroxyl radicals generated by alloxan.

    PubMed

    Brömme, H J; Mörke, W; Peschke, D; Ebelt, H; Peschke, D

    2000-11-01

    Alloxan can act as a generator of reactive oxygen species (ROS) as long as sufficient suitable reducing agents (e.g. reduced glutathione) and oxygen are available. Using electron spin resonance-spectroscopy and the oxygen-centered spin trap DEPMPO, we demonstrate that hydroxyl radicals (OH.) are formed in vitro by alloxan in the presence of glutathione (GSH) and chelated divalent iron. Furthermore, peroxidation of polyunsaturated fatty acids from phosphatidylcholine-containing liposomes with concomitant formation of malondialdehyde (MDA) was used as a further indicator for a preceding OH. formation. Melatonin, the main secretory product of the pineal gland, is an effective scavenger of OH.. The 50%-inhibitor concentration (IC50-value) for melatonin to scavenge OH. generated from the alloxan/GSH-reaction in the presence of ferrous ions was 23 micromol/L. In contrast to the ability to effectively scavenge OH., the potential of melatonin to prevent lipid peroxidation is considerably less pronounced. PMID:11068942

  1. MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective.

    PubMed

    Liu, Jiabei; Clough, Shannon J; Hutchinson, Anthony J; Adamah-Biassi, Ekue B; Popovska-Gorevski, Marina; Dubocovich, Margarita L

    2016-01-01

    Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein-coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents. PMID:26514204

  2. MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective.

    PubMed

    Liu, Jiabei; Clough, Shannon J; Hutchinson, Anthony J; Adamah-Biassi, Ekue B; Popovska-Gorevski, Marina; Dubocovich, Margarita L

    2016-01-01

    Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein-coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents.

  3. Effect of melatonin on kidney cold ischemic preservation injury

    PubMed Central

    Aslaner, Arif; Gunal, Omer; Turgut, Hamdi Taner; Celik, Erdal; Yildirim, Umran; Demirci, Rojbin Karakoyun; Gunduz, Umut Riza; Calis, Hasan; Dogan, Sami

    2013-01-01

    Melatonin is a potent free radical scavenger of reactive oxygen species, nitric oxide synthase inhibitor and a well-known antioxidant secreted from pineal gland. This hormone has been reported to protect tissue from oxidative damage. In this study, we aim to investigate the effect of melatonin on kidney cold ischemia time when added to preservation solution. Thirty male Wistar albino rats were divided equally into three groups; Ringer Lactate (RL) solution, University of Wisconsin (UW) solution with and without melatonin. The serum Lactate Dehydrogenase (LDH) activities of the preservation solutions at 2nd, 24th, 36th, and 48th hours were determined. Tissue malondialdehyde (MDA) levels were also measured and a histological examination was performed at 48th hour. Melatonin that added to preservation solution prevented enzyme elevation and decreased lipid peroxidation in preservation solution when compared to the control group (p<0.05). The histological examination revealed that UW solution containing melatonin significantly prevented the kidney from pathological injury (p<0.05). Melatonin added to preservation solutions such as UW solution seemed to protect the tissue preserved effectively from cold ischemic injury for up to 48 hour. PMID:24179573

  4. MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective

    PubMed Central

    Liu, Jiabei; Clough, Shannon J.; Hutchinson, Anthony J.; Adamah-Biassi, Ekue B.; Popovska-Gorevski, Marina; Dubocovich, Margarita L.

    2016-01-01

    Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein–coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents. PMID:26514204

  5. The role of melatonin and serotonin in aging: update.

    PubMed

    Grad, B R; Rozencwaig, R

    1993-01-01

    It has been proposed that aging occurs because of a failure of the pineal gland to produce melatonin from serotonin each day beginning at sunset and throughout the night. This lack leads to a nighttime deficiency of melatonin both absolutely and also relatively to serotonin. As melatonin has wide-spread integrative and regenerative effects, its lack may lead to disturbances normally associated with aging. The present paper reviews the pertinent literature which appeared since our first publication, but earlier articles are also included. Evidence is presented for a role of melatonin and serotonin in controlling the neuroendocrine and immune networks and in inhibiting the development of ischemic heart and Alzheimer's disease, tumor formation and other degenerative processes associated with aging. The possible role of melatonin in the favourable effects of dietary restriction on aging is also discussed. This paper provides additional evidence that a melatonin deficiency, especially in relation to serotonin, may be responsible for the promotion of aging in the organism. PMID:8292130

  6. Melatonin directly interacts with cholesterol and alleviates cholesterol effects in dipalmitoylphosphatidylcholine monolayers.

    PubMed

    Choi, Youngjik; Attwood, Simon J; Hoopes, Matthew I; Drolle, Elizabeth; Karttunen, Mikko; Leonenko, Zoya

    2014-01-01

    Melatonin is a pineal hormone that has been shown to have protective effects in several diseases that are associated with cholesterol dysregulation, including cardiovascular disease, Alzheimer's disease, and certain types of cancers. Cholesterol is a major membrane constituent with both a structural and functional influence. It is also known that melatonin readily partitions into cellular membranes. We investigated the effects of melatonin and cholesterol on the structure and physical properties of a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayer as a simple membrane model using the Langmuir-Blodgett (L-B) monolayer technique and molecular dynamics (MD) simulations. We report that melatonin increases the area per lipid and elastic compressibility of the DPPC monolayer in a concentration dependent manner, while cholesterol has the opposite effect. When both melatonin and cholesterol were present in the monolayer, the compression isotherms showed normalization of the area per molecule towards that of the pure DPPC monolayer, thus indicating that melatonin counteracts and alleviates cholesterol's effects. Atomistic MD simulations of melatonin enriched DPPC systems correlate with our experimental findings and illustrate the structural effects of both cholesterol and melatonin. Our results suggest that melatonin is able to lessen the influence of cholesterol through two different mechanisms. Firstly, we have shown that melatonin has a fluidizing effect on monolayers comprising only lipid molecules. Secondly, we also observe that melatonin interacts directly with cholesterol. Our findings suggest a direct nonspecific interaction of melatonin may be a mechanism involved in reducing cholesterol associated membrane effects, thus suggesting the existence of a new mechanism of melatonin's action. This may have important biological relevance in addition to the well-known anti-oxidative and receptor binding effects. PMID:24651707

  7. Effect of melatonin in the rat tail artery: role of K+ channels and endothelial factors

    PubMed Central

    Geary, Greg G; Duckles, Sue P; Krause, Diana N

    1998-01-01

    The role of endothelial factors and potassium channels in the action of the pineal hormone melatonin to potentiate vasoconstrictor responses was investigated in the isolated perfused tail artery of the rat.Melatonin (100 nM) potentiated contractile responses to both adrenergic nerve stimulation and α1-adrenoceptor stimulation by phenylephrine. After removal of the endothelium, melatonin no longer caused potentiation.The potentiating effect of melatonin was also lost when nitric oxide synthase was inhibited with L-NAME (10 nM). Thus potentiating effects depend on the presence of nitric oxide released by the endothelium. However, melatonin did not affect relaxation responses to acetylcholine in endothelium-intact arteries, nor did melatonin modulate relaxing responses to sodium nitroprusside in endothelium-denuded arteries. While melatonin does not appear to modulate agonist-induced release of nitric oxide nor its effect, melatonin may modulate nitric oxide production induced by flow and shear stress.When the Ca2+-activated K+ channel opener, NS 1619 (10 μM), was present, potentiating effects of melatonin were restored in endothelium-denuded vessels. However, addition of the opener of ATP-sensitive K+ channels, cromakalim (3 μM), did not have the same restorative effect. Furthermore, addition of a blocker of Ca2+-activated K+ channels, tetraethylammonium (1 mM), significantly attenuated potentiating effects of melatonin. These findings support the hypothesis that melatonin inhibits the activity of large conductance Ca2+-activated K+ channels to produce its potentiating effects.Thus in the rat perfused tail artery, potentiation of constriction by melatonin depends on the activity of both endothelial factors and Ca2+-activated K+ channels. Our findings suggest that melatonin inhibits endothelial K+ channels to decrease flow-induced release of nitric oxide as well as block smooth muscle K+ channels to enhance vascular tone. PMID:9605558

  8. Melatonin protects skin keratinocyte from hydrogen peroxide-mediated cell death via the SIRT1 pathway

    PubMed Central

    Lee, Ju-Hee; Moon, Ji-Hong; Nazim, Uddin MD.; Lee, You-Jin; Seol, Jae-Won; Eo, Seong-Kug; Lee, John-Hwa; Park, Sang-Youel

    2016-01-01

    Melatonin (N-acetyl-5-methoxytryptamine), which is primarily synthesized in and secreted from the pineal gland, plays a pivotal role in cell proliferation as well as in the regulation of cell metastasis and cell survival in a diverse range of cells. The aim of this study is to investigate protection effect of melatonin on H2O2-induced cell damage and the mechanisms of melatonin in human keratinocytes. Hydrogen peroxide dose-dependently induced cell damages in human keratinocytes and co-treatment of melatonin protected the keratinocytes against H2O2-induced cell damage. Melatonin treatment activated the autophagy flux signals, which were identified by the decreased levels of p62 protein. Inhibition of autophagy flux via an autophagy inhibitor and ATG5 siRNA technique blocked the protective effects of melatonin against H2O2-induced cell death in human keratinocytes. And we found the inhibition of sirt1 using sirtinol and sirt1 siRNA reversed the protective effects of melatonin and induces the autophagy process in H2O2-treated cells. This is the first report demonstrating that autophagy flux activated by melatonin protects human keratinocytes through sirt1 pathway against hydrogen peroxide-induced damages. And this study also suggest that melatonin could potentially be utilized as a therapeutic agent in skin disease. PMID:26918354

  9. Effects of melatonin on water metabolism and renal function in male Syrian hamsters (Mesocricetus auratus).

    PubMed

    Richardson, B A; Studier, E H; Stallone, J N; Kennedy, C M

    1992-09-01

    The pineal indoleamine, melatonin, has been shown to influence many physiological systems within the mammalian body. Few studies, however, have examined the influence of melatonin on renal function. This study investigated the effects of melatonin on water metabolism and renal function. Young adult male Syrian hamsters were maintained on a long photoperiod (LD 14:10) in metabolic cages. The animals received daily (1700) injections of either control vehicle or 25 micrograms of melatonin for 85 consecutive days. Melatonin administration resulted in significant increases in water consumption and urine production. Water budgets were also significantly influenced by melatonin, as were urinary osmolality, urinary sodium, and potassium concentrations, but urinary calcium concentrations were essentially unaltered. When excretion rates for sodium, potassium, and calcium were calculated, no differences were observed between the vehicle control and melatonin-treated groups. Injections of melatonin also significantly decreased plasma antidiuretic hormone (ADH). These results demonstrate that afternoon injections of melatonin can alter renal function, which may involve direct (i.e., on ADH secretion and/or thirst mechanisms) or indirect (i.e., behavioral) effects. PMID:1453309

  10. A melatonin-independent seasonal timer induces neuroendocrine refractoriness to short day lengths.

    PubMed

    Butler, Matthew P; Turner, Kevin W; Zucker, Irving

    2008-06-01

    The duration of nocturnal pineal melatonin secretion transduces effects of day length (DL) on the neuroendocrine axis of photoperiodic rodents. Long DLs support reproduction, and short DLs induce testicular regression, followed several months later by spontaneous recrudescence; gonadal regrowth is thought to reflect development of tissue refractoriness to melatonin. In most photoperiodic species, pinealectomy does not diminish reproductive competence in long DLs. Turkish hamsters (Mesocricetus brandti) deviate from this norm: elimination of melatonin secretion in long-day males by pinealectomy or constant light treatment induces testicular regression and subsequently recrudescence; the time course of these gonadal transitions is similar to that observed in males transferred from long to short DLs. In the present study, long-day Turkish hamsters that underwent testicular regression and recrudescence in constant light subsequently were completely unresponsive to the antigonadal effects of short DLs. Other hamsters that manifested testicular regression and recrudescence in short DLs were unresponsive to the antigonadal effects of pinealectomy or constant light. Long-term suppression of melatonin secretion induces a physiological state in Turkish hamsters similar or identical to the neuroendocrine refractoriness produced by short-day melatonin signals (i.e., neural refractoriness to melatonin develops in the absence of circulating melatonin secretion). A melatonin-independent interval timer, which would remain operative in the absence of melatonin during hibernation, may determine the onset of testicular recrudescence in the spring. In this respect, Turkish hamsters differ from most other photoperiodic rodents.

  11. Expression and cellular localizaion of melatonin-synthesizing enzymes in rat and human salivary glands.

    PubMed

    Shimozuma, Masashi; Tokuyama, Reiko; Tatehara, Seiko; Umeki, Hirochika; Ide, Shinji; Mishima, Kenji; Saito, Ichiro; Satomura, Kazuhito

    2011-04-01

    Melatonin, discovered in 1958, is secreted by the pineal gland primarily during the night. Its secretion is controlled by the light/dark cycle of the environment. Melatonin is also produced in and secreted by various extrapineal organs, tissues and cells and its synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT) is expressed in various extrapineal organs, tissues and cells. Recently, it was reported that melatonin is present in saliva, but it is not certain where melatonin was synthesized and whether it was secreted into saliva and what function it may have in saliva. The present study was performed to investigate where melatonin was synthesized and whether it was secreted by salivary glands into saliva. We performed immunohistochemical analysis of the expression of AANAT in rat parotid, submandibular and sublingual glands and the expression of both AANAT and hydroxyindole-O-methyltransferase (HIOMT) in human submandibular glands. We evaluated the expression of AANAT and HIOMT mRNA in rat submandibular glands by quantitative reverse transcription-polymerase chain reaction. As a result, we observed expression of AANAT in epithelial cells of striated ducts in rat salivary glands and expression of AANAT, HIOMT and melatonin in epithelial cells of striated ducts in human submandibular glands. In addition, we also confirmed the expression of the most potent melatonin receptor, melatonin 1a receptor, in rat buccal mucosa. Our findings suggest that melatonin might be produced and secreted by salivary glands directly into saliva and that it might play some physiological role in the oral cavity.

  12. Effects of melatonin on water metabolism and renal function in male Syrian hamsters (Mesocricetus auratus).

    PubMed

    Richardson, B A; Studier, E H; Stallone, J N; Kennedy, C M

    1992-09-01

    The pineal indoleamine, melatonin, has been shown to influence many physiological systems within the mammalian body. Few studies, however, have examined the influence of melatonin on renal function. This study investigated the effects of melatonin on water metabolism and renal function. Young adult male Syrian hamsters were maintained on a long photoperiod (LD 14:10) in metabolic cages. The animals received daily (1700) injections of either control vehicle or 25 micrograms of melatonin for 85 consecutive days. Melatonin administration resulted in significant increases in water consumption and urine production. Water budgets were also significantly influenced by melatonin, as were urinary osmolality, urinary sodium, and potassium concentrations, but urinary calcium concentrations were essentially unaltered. When excretion rates for sodium, potassium, and calcium were calculated, no differences were observed between the vehicle control and melatonin-treated groups. Injections of melatonin also significantly decreased plasma antidiuretic hormone (ADH). These results demonstrate that afternoon injections of melatonin can alter renal function, which may involve direct (i.e., on ADH secretion and/or thirst mechanisms) or indirect (i.e., behavioral) effects.

  13. Nocturnal melatonin secretion in multiple sclerosis patients with affective disorders.

    PubMed

    Sandyk, R; Awerbuch, G I

    1993-02-01

    The pineal gland has been implicated recently in the pathogenesis of multiple sclerosis (MS), a chronic demyelinating disease of CNS. Since nocturnal melatonin secretion is low in some groups of patients with mental depression, we predicted lower melatonin secretion in MS patients with history of affective illness compared to those without psychiatric disorders. To test this hypothesis, we studied single nocturnal plasma melatonin levels and the incidence of pineal calcification (PC) on CT scan in a cohort of 25 MS patients (4 men, 21 women; mean age = 39.4 years, SD = 9.3), 15 of whom had a history of coexisting psychiatric disorders with predominant affective symptomatology. Other factors that may be related to depression such as vitamin B12, folic acid, zinc, magnesium, and homocysteine, were also included in the analysis. Neither any of the metabolic factors surveyed nor the incidence of PC distinguished the psychiatric from the control group. However, the mean melatonin level in the psychiatric patients was significantly lower than in the control group. Since low melatonin secretion in patients with depression may be related to a phase-advance of the circadian oscillator regulating the offset of melatonin secretion, we propose that the depression of MS likewise may reflect the presence of dampened circadian oscillators. Furthermore, since exacerbation of motor symptoms in MS patients may be temporally related to worsening of depression, we propose that circadian phase lability may also underlie the relapsing-remitting course of the disease. Consequently, pharmacological agents such as lithium or bright light therapy, which have been shown to phase-delay circadian rhythms, might be effective in the treatment of affective symptoms in MS as well as preventing motor exacerbation and hastening a remission from an acute attack. PMID:8063528

  14. Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain

    PubMed Central

    2011-01-01

    Background The mammalian suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish cyclops (cyc) mutants lack ventral brain, including the region that gives rise to the SCN. We have used cyc embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression. Results We find that pineal rhythms are present in cyc mutants despite the absence of an SCN. The arginine vasopressin-like protein (Avpl, formerly called Vasotocin) is a peptide hormone expressed in and around the SCN. We find avpl mRNA is absent in cyc mutants, supporting previous work suggesting the SCN is missing. In contrast, expression of the putative circadian clock genes, cryptochrome 1b (cry1b) and cryptochrome 3 (cry3), in the brain of the developing fish is unaltered. Expression of two pineal rhythmic genes, exo-rhodopsin (exorh) and serotonin-N-acetyltransferase (aanat2), involved in photoreception and melatonin synthesis, respectively, is also similar between cyc embryos and their wildtype (WT) siblings. The timing of the peaks and troughs of expression are the same, although the amplitude of expression is slightly decreased in the mutants. Cyclic gene expression persists for two days in cyc embryos transferred to constant light or constant dark, suggesting a circadian clock is driving the rhythms. However, the amplitude of rhythms in cyc mutants kept in constant conditions decreased more quickly than in their WT siblings

  15. Radionuclide Imaging of Neurohormonal System of the Heart

    PubMed Central

    Chen, Xinyu; Werner, Rudolf A.; Javadi, Mehrbod S.; Maya, Yoshifumi; Decker, Michael; Lapa, Constantin; Herrmann, Ken; Higuchi, Takahiro

    2015-01-01

    Heart failure is one of the growing causes of death especially in developed countries due to longer life expectancy. Although many pharmacological and instrumental therapeutic approaches have been introduced for prevention and treatment of heart failure, there are still limitations and challenges. Nuclear cardiology has experienced rapid growth in the last few decades, in particular the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET), which allow non-invasive functional assessment of cardiac condition including neurohormonal systems involved in heart failure; its application has dramatically improved the capacity for fundamental research and clinical diagnosis. In this article, we review the current status of applying radionuclide technology in non-invasive imaging of neurohormonal system in the heart, especially focusing on the tracers that are currently available. A short discussion about disadvantages and perspectives is also included. PMID:25825596

  16. Genomic variation and neurohormonal intervention in heart failure.

    PubMed

    McNamara, Dennis M

    2010-01-01

    Neurohormonal activation is an important driver of heart-failure progression, and all pharmacologic interventions that improve heart-failure survival inhibit this systemic response to myocardial injury. Adrenergic stimulation of beta(1) receptors in the kidney results in the release of plasma renin, the conversion of peptide precursors to angiotensin II (a2), and ultimately the production of aldosterone. beta(1)-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and aldosterone receptor antagonists all act by inhibiting the activity of critical protein of this core pathway: the beta(1) receptor, ACE, the a2 receptor, and aldosterone synthase. Investigation of the pharmacogenetic interactions of the ACE D/I polymorphism and heart-failure therapy demonstrates the power of genomics to target therapeutics. This review explores how genetic variation in genes involved in neurohormonal activation influences heart-failure outcomes and the impact of pharmacotherapy.

  17. Pineal-independent regulation of photo-nonresponsiveness in the Siberian hamster (Phodopus sungorus).

    PubMed

    Prendergast, B J; Freeman, D A

    1999-02-01

    The pineal hormone melatonin influences circadian rhythms and also mediates reproductive responses to photoperiod. The authors tested whether pinealectomy influences circadian oscillators responsible for induction of nonresponsiveness to short day lengths by preventing normal short-day patterns of circadian entrainment. Adult male Siberian hamsters were pinealectomized or sham operated, maintained in either 18 h light per day (18L) or 15L for 10 weeks, and then tested for responsiveness to 10L. Because pinealectomized hamsters do not show gonadal regression in short day lengths, responsiveness was assessed by measuring phase angle of entrainment and the length of the nightly activity period following transfer to 10L. The incidence of nonresponsiveness was significantly higher in 18L hamsters than in 15L hamsters but was unaffected by pineal status. Fully 88% of 18L hamsters failed to entrain to 10L in the normal short-day manner; the duration of nightly activity remained compressed, and the phase angle of entrainment was large and negative relative to lights off. The 15L hamsters entrained normally to 10L. Exposure to constant light after 10L treatment was equally effective in inducing arrhythmicity in pinealectomized and intact hamsters. Changes in the period of morning and evening circadian oscillators subsequent to 18L treatment did not predict circadian responsiveness to short photoperiod. Long-day induction of photo-nonresponsiveness, which prevents winter responses to short day lengths, occurs independently of pineal melatonin feedback on the circadian system.

  18. Expression and regulation of Icer mRNA in the Syrian hamster pineal gland.

    PubMed

    Diaz, Elena; Garidou, Marie-Laure; Dardente, Hugues; Salingre, Anthony; Pévet, Paul; Simonneaux, Valérie

    2003-04-10

    Inducible-cAMP early repressor (ICER) is a potent inhibitor of CRE (cAMP-related element)-driven gene transcription. In the rat pineal gland, it has been proposed to be part of the mechanisms involved in the shutting down of the transcription of the gene coding for arylalkylamine N-acetyltransferase (AA-NAT, the melatonin rhythm-generating enzyme). In this study, we report that ICER is expressed in the pineal gland of the photoperiodic rodent Syrian hamster although with some difference compared to the rat. In the Syrian hamster pineal, Icer mRNA levels, low at daytime, displayed a 20-fold increase during the night. Nighttime administration of a beta-adrenergic antagonist, propranolol, significantly reduced Icer mRNA levels although daytime administration of a beta-adrenergic agonist, isoproterenol, was unable to raise the low amount of Icer mRNA. These observations indicate that Icer mRNA expression is induced by the clock-driven norepinephrine release and further suggest that this stimulation is restricted to nighttime, as already observed for Aa-nat gene transcription. Furthermore, we found that the daily profile of Icer mRNA displayed photoperiodic variation with a lengthening of the nocturnal peak in short versus long photoperiod. These data indicate that ICER may be involved in both daily and seasonal regulation of melatonin synthesis in the Syrian hamster.

  19. Ultrastructural interrelationship between the pineal gland and the testis in the male rat.

    PubMed

    Kuş, I; Sarsilmaz, M; Ogetürk, M; Yilmaz, B; Keleştimur, H; Oner, H

    2000-01-01

    The ultrastructural interrelationship between the pineal gland and testis was evaluated in the rat. Wistar rats were divided into 6 groups. Groups I and II were sham-orchidectomized and orchidectomized rats, respectively. Rats in group III were orchidectomized and daily injected with testosterone propionate (TP) for 1 month. Groups IV and V were sham-pinealectomized and pinealectomized, respectively. Group VI was pinealectomized and daily injected with melatonin for 2 months. All animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II, and III and the testes of groups IV, V, and VI were removed and weighed. All specimens were examined by electron microscopy. Orchidectomy caused an increase of lipid droplets, cytoplasmic dense bodies, and lysosomes. Rough endoplasmic reticulum, Golgi apparatus, and mitochondria were extensive in the cytoplasm. TP administration to orchidectomized rats resulted in formation of less extensive lipid droplets and mitochondria. In pinealectomized rats, golgi complex, mitochondria, and enlarged smooth endoplasmic reticulum were extensive in the cytoplasm of Leydig cells. Formation of cytoplasmic secretory granules and osmiophilic bodies was observed. Testicular weight increased compared to group IV. Melatonin decreased testicular weight in comparison to group V and prevented ultrastructural changes. Pinealectomy and orchidectomy caused hyperactivity in Leydig cells and pinealocytes, respectively, which suggests a mutual relationship between the pineal gland and testis in the rat.

  20. Tumors of the pineal region.

    PubMed

    Piovan, E; Beltramello, A

    1996-01-01

    The role played by neuroradiologic examinations in the diagnosis of neoformations of the pineal region is considered. Results of reports of literature are compared with the personal experience (40 patients) to draw possible significant conclusions for the diagnosis of the oncological type. First, intrinsic pineal lesions should be separated from those of adjacent structures. Reliable discriminating parameters useful in the differential diagnosis are represented by sex and age. Diagnosis based on biochemistry with markers was shown not to be univocal. A further separation can be based on CT and MRI findings. In particular, teratomas appear as solid tumors with calcification and fat. The latter is depicted on MRI even if minimal. To the contrary, germinomas do not contain fat and are markedly enhancing. Microcysts seem to be more common in tumors originating from parenchymal pineal cells. A reliable differential diagnosis is however possible only for small-sized lesions where identification of the anatomical structure of origin is easier. PMID:8677341

  1. Association of mast cells with calcification in the human pineal gland.

    PubMed

    Maślińska, Danuta; Laure-Kamionowska, Milena; Deręgowski, Krzysztof; Maśliński, Sławomir

    2010-01-01

    Increased pineal calcifications and decreased pineal melatonin biosynthesis, both age related, support the notion of a pineal bio-organic timing mechanism. The role of calcification in the pathogenesis of pineal gland dysfunction remains unknown but the available data document that calcification is an organized, regulated process, rather than a passive aging phenomenon. The cellular biology and micro-environmental conditions required for calcification remain poorly understood but most studies have demonstrated evidence that mast cells are strongly implicated in this process. The aim of the present study was to examine the phenotype of mast cells associated with early stages and with the progressive development of calcification in the human pineal gland. The study was performed on pineal samples of 170 fetuses and children whose brains were autopsied and diagnosed during 1998-2002. The representative cerebral and pineal specimens were stained with haematoxylin and eosin or the von Kossa staining technique and for the distribution of mast cell tryptase, mast cell chymase, histamine H4 receptor and vascular network using biotinylated Ulex europaeus agglutinin. Tryptase mast cells were found in all stages of pineal gland development independently of the presence of local tissue lesions. All of them were always localized in the close vicinity of the blood vessels and expressed immunoreactivity to histamine H4 receptor antibody. Immunolocalization of mast cells by chymase antibody (and following dual immunostaining with both chymase and tryptase antibodies) demonstrated that these cells were few in number and were located in the subcapsular region of the gland. In our study, all functional mast cells that underwent activation and were co-localized with deposits of calcium did not contain chymase. All of them were stained with tryptase and represent the MC-T phenotype. Tryptase mast cells and extracellular tryptase were often associated with areas of early and more

  2. Association of mast cells with calcification in the human pineal gland.

    PubMed

    Maślińska, Danuta; Laure-Kamionowska, Milena; Deręgowski, Krzysztof; Maśliński, Sławomir

    2010-01-01

    Increased pineal calcifications and decreased pineal melatonin biosynthesis, both age related, support the notion of a pineal bio-organic timing mechanism. The role of calcification in the pathogenesis of pineal gland dysfunction remains unknown but the available data document that calcification is an organized, regulated process, rather than a passive aging phenomenon. The cellular biology and micro-environmental conditions required for calcification remain poorly understood but most studies have demonstrated evidence that mast cells are strongly implicated in this process. The aim of the present study was to examine the phenotype of mast cells associated with early stages and with the progressive development of calcification in the human pineal gland. The study was performed on pineal samples of 170 fetuses and children whose brains were autopsied and diagnosed during 1998-2002. The representative cerebral and pineal specimens were stained with haematoxylin and eosin or the von Kossa staining technique and for the distribution of mast cell tryptase, mast cell chymase, histamine H4 receptor and vascular network using biotinylated Ulex europaeus agglutinin. Tryptase mast cells were found in all stages of pineal gland development independently of the presence of local tissue lesions. All of them were always localized in the close vicinity of the blood vessels and expressed immunoreactivity to histamine H4 receptor antibody. Immunolocalization of mast cells by chymase antibody (and following dual immunostaining with both chymase and tryptase antibodies) demonstrated that these cells were few in number and were located in the subcapsular region of the gland. In our study, all functional mast cells that underwent activation and were co-localized with deposits of calcium did not contain chymase. All of them were stained with tryptase and represent the MC-T phenotype. Tryptase mast cells and extracellular tryptase were often associated with areas of early and more

  3. Elevated heart rate and nondipping heart rate as potential targets for melatonin: a review.

    PubMed

    Simko, Fedor; Baka, Tomas; Paulis, Ludovit; Reiter, Russel J

    2016-09-01

    Elevated heart rate is a risk factor for cardiovascular and all-cause mortalities in the general population and various cardiovascular pathologies. Insufficient heart rate decline during the night, that is, nondipping heart rate, also increases cardiovascular risk. Abnormal heart rate reflects an autonomic nervous system imbalance in terms of relative dominance of sympathetic tone. There are only a few prospective studies concerning the effect of heart rate reduction in coronary heart disease and heart failure. In hypertensive patients, retrospective analyses show no additional benefit of slowing down the heart rate by beta-blockade to blood pressure reduction. Melatonin, a secretory product of the pineal gland, has several attributes, which predict melatonin to be a promising candidate in the struggle against elevated heart rate and its consequences in the hypertensive population. First, melatonin production depends on the sympathetic stimulation of the pineal gland. On the other hand, melatonin inhibits the sympathetic system in several ways representing potentially the counter-regulatory mechanism to normalize excessive sympathetic drive. Second, administration of melatonin reduces heart rate in animals and humans. Third, the chronobiological action of melatonin may normalize the insufficient nocturnal decline of heart rate. Moreover, melatonin reduces the development of endothelial dysfunction and atherosclerosis, which are considered a crucial pathophysiological disorder of increased heart rate and pulsatile blood flow. The antihypertensive and antiremodeling action of melatonin along with its beneficial effects on lipid profile and insulin resistance may be of additional benefit. A clinical trial investigating melatonin actions in hypertensive patients with increased heart rate is warranted.

  4. Prospective Study on Salivary Evening Melatonin and Sleep before and after Pinealectomy in Humans.

    PubMed

    Slawik, Helen; Stoffel, Michael; Riedl, Lina; Veselý, Zdenko; Behr, Michael; Lehmberg, Jens; Pohl, Corina; Meyer, Bernhard; Wiegand, Michael; Krieg, Sandro M

    2016-02-01

    Melatonin is secreted systemically from the pineal gland maximally at night but is also produced locally in many tissues. Its chronobiological function is mainly exerted by pineal melatonin. It is a feedback regulator of the main circadian pacemaker in the hypothalamic suprachiasmatic nuclei and of many peripheral oscillators. Although exogenous melatonin is approved for circadian rhythm sleep disorders and old-age insomnia, research on endogenous melatonin in humans is hindered by the great interindividual variability of its amount and circadian rhythm. Single case studies on pinealectomized patients report on disrupted but also hypersomnic sleep. This is the first systematic prospective report on sleep with respect to pinealectomy due to pinealocytoma World Health Organization grade I without chemo- or radiotherapy. Before and after pinealectomy, 8 patients completed questionnaires on sleep quality and circadian rhythm (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Morningness-Eveningness Questionnaire), 2 nights of polysomnography, salivary evening melatonin profiles, and qualitative assessment of 2 weeks of actigraphy and sleep logs. Six patients were assessed retrospectively up to 4 years after pinealectomy. Before pinealectomy, all but 1 patient showed an evening melatonin rise typical for indifferent chronotypes. After pinealectomy, evening saliva melatonin was markedly diminished, mostly below the detection limit of the assay (0.09 pg/mL). No systematic change in subjective sleep quality or standard measures of polysomnography was found. Mean pre- and postoperative sleep efficiency was 94% and 95%, and mean sleep-onset latency was 21 and 17 min, respectively. Sleep-wake rhythm during normal daily life did not change. Retrospective patients had a reduced sleep efficiency (90%) and more stage changes, although this was not significantly different from prospective patients. In conclusion, melatonin does seem to have a modulatory, not a

  5. Rhodopsin expression in the zebrafish pineal gland from larval to adult stage.

    PubMed

    Magnoli, Domenico; Zichichi, Rosalia; Laurà, Rosaria; Guerrera, Maria Cristina; Campo, Salvatore; de Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

    2012-03-01

    The zebrafish pineal gland plays an important role in different physiological functions including the regulation of the circadian clock. In the fish pineal gland the pinealocytes are made up of different segments: outer segment, inner segment and basal pole. Particularly, in the outer segment the rhodopsin participates in the external environment light reception that represents the first biochemical step in the melatonin production. It is well known that the rhodopsin in the adult zebrafish is well expressed in the pineal gland but both the expression and the cellular localization of this protein during development remain still unclear. In this study using qRT-PCR, sequencing and immunohistochemistry the expression as well as the protein localization of the rhodopsin in the zebrafish from larval (10 dpf) to adult stage (90 dpf) were demonstrated. The rhodopsin mRNA expression presents a peak of expression at 10 dpf, a further reduction to 50 dpf before increasing again in the adult stage. Moreover, the cellular localization of the rhodopsin-like protein was always localized in the pinealocyte at all ages examined. Our results demonstrated the involvement of the rhodopsin in the zebrafish pineal gland physiology particularly in the light capture during the zebrafish lifespan.

  6. /sup 3/H-retinol derived photopigment in chick pineal membranes

    SciTech Connect

    Wallingford, J.; Zatz, M.

    1986-05-01

    Pineal glands display a day-night rhythm in the synthesis and secretion of melatonin. Dispersed chick pinealocytes retain their ability to respond to light in vitro for at least a week. Pinealocytes incubated overnight with /sup 3/H-retinol in the dark incorporate radioactivity predominantly into retinyl esters. To identify the chick pineal photopigment, SDS-PAGE was performed on radiolabelled preparations of pinealocytes and (intraocularly injected) rat retina. When intact cells or membrane preparations of cultured cells were incubated with NaCNBH/sub 3/, in the dark, a single radioactive peak with an apparent molecular weight of 32,000 daltons was observed. Rat retina preparations revealed a major peak at approximately 40,000 daltons. Protease inhibitors were present in the workup, and radioactivity corresponding to the smaller peak from pineal was not observed in retina. There was no radioactive peak when NaCNBH/sub 3/ was omitted. When samples were boiled in SDS the radioactivity shifted to the origin. These data suggest a protein in pinealocyte membranes which binds retinoid via a Schiff's base. Exposure to light of deoxycholate solubilized pineal membranes reduced the radioactivity associated with the protein. These findings raise the possibility that this protein is the pinealocyte's photopigment. Photopigments smaller than those observed in mammals have been reported in invertebrates.

  7. Retinal, pineal and diencephalic expression of frog arylalkylamine N-acetyltransferase-1.

    PubMed

    Isorna, Esther; Besseau, Laurence; Boeuf, Gilles; Desdevises, Yves; Vuilleumier, Robin; Alonso-Gómez, Angel L; Delgado, María J; Falcón, Jack

    2006-06-27

    The arylalkylamine N-acetyltransferase (AANAT) is a key enzyme in the rhythmic production of melatonin. Two Aanats are expressed in Teleost fish (Aanat1 in the retina and Aanat2 in the pineal organ) but only Aanat1 is found in tetrapods. This study reports the cloning of Aanat1 from R. perezi. Transcripts were mainly expressed in the retina, diencephalon, intestine and testis. In the retina and pineal organ, Aanat1 expression was in the photoreceptor cells. Expression was also seen in ependymal cells of the 3rd ventricle and discrete cells of the suprachiasmatic area. The expression of Aanat1 in both the retina and pineal organ, and the absence of Aanat2 suggests that green frog resembles more to birds and mammals than to Teleost fish, as far as Aanat is concerned. The significance of Aanat1 in extra-pineal and extra-retinal tissues remains to be elucidated; in the diencephalon, it might be associated to the so-called deep brain photoreceptor cells.

  8. Duration of melatonin regulates seasonal plasticity in subtropical Indian weaver bird, Ploceus philippinus.

    PubMed

    Surbhi; Kumari, Yatinesh; Rani, Sangeeta; Tsutsui, Kazuyoshi; Kumar, Vinod

    2015-09-01

    Day length regulates seasonal plasticity connected with reproduction in birds. Rhythmic pineal melatonin secretion is a reliable indicator of the night length, hence day length. Removal of rhythmic melatonin secretion by exposure to constant bright light (LLbright) or by pinealectomy renders several species of songbirds including Indian weaver bird (Ploceus philippinus) arrhythmic. Present study investigated whether rhythmic melatonin is involved in the regulation of key reproductive neuropeptides (GnRH I and GnIH) and reproduction linked neural changes, viz. song control nuclei, in Indian weaver birds. Two experiments were performed using birds in an arrhythmic condition with low (under LLbright) or no (in the absence of pineal gland) endogenous melatonin. In experiment I, three groups of birds (n=5 each) entrained to 12L:12D were exposed to LLbright (25lux) for two weeks. Beginning on day 15 of LLbright, a control group received vehicle for 16h and two treatment groups were given melatonin in drinking water for 8h or 16h. In experiment II, one group of sham-operated and three groups of pinealectomized birds (n=5 each) entrained to 12L:12D were exposed to constant dim light (LLdim, 0.5lux). Beginning on day 15 of LLdim, three groups received similar treatment as in experiment I. Birds were perfused after thirty cycles of the melatonin treatment, and brain sections were immunohistochemically double-labeled for GnRH I and GnIH or Nissl stained. Activity was recorded throughout the experiments, while body mass and testes were measured at the beginning and end of the experiment. Birds were synchronized with melatonin cycles and measured the duration of melatonin as "night". Pinealectomized birds that received 16h of melatonin had significantly higher GnIH-ir cells than those received 8h melatonin; there was no difference in the GnRH I immunoreactivity between two treatment groups however. Intact birds that received long duration melatonin cycles exhibited small song

  9. Melatonin and clinical application.

    PubMed

    Wetterberg, L

    1999-01-01

    A review of the different publications dealing with melatonin in humans shows that this field has been very active in the last few years. Normative melatonin values have been defined. Various relationships between melatonin and other traits have been studied, such as sleep, circadian rhythm, surgical stress and anaesthesia. Age-related melatonin studies and melatonin during depression and other psychiatric disorders have been reviewed. Finally, some studies have been performed to use melatonin as a medication for sleep disturbance in depression, for jet-lag and as a skin protector for ultraviolet light. PMID:10420439

  10. Ototoxicity caused by aminoglycosides is ameliorated by melatonin without interfering with the antibiotic capacity of the drugs.

    PubMed

    Lopez-Gonzalez, M A; Guerrero, J M; Torronteras, R; Osuna, C; Delgado, F

    2000-01-01

    The production of free radicals seems to be involved in the mechanisms of ototoxicity. Aminoglycosides produce ototoxicity, which can be determined through distortion product otoacoustic emissions (OAEs) that measure the activity of the outer hair cells of the organ of Corti. An ototoxic chart was obtained in rats using gentamicin or tobramycin. Together with this treatment, the animals ingested melatonin in the drinking water, or melatonin was injected subcutaneously or intramuscularly. The distortion product OAEs were determined over a prolonged period of time for each of the groups. The effect of melatonin on the antibiotic capacity of the aminoglycosides used was also studied. Antibiograms inoculated with Escherichia coli or Pseudomonas aeruginosa and treated with gentamicin or tobramycin in the presence or absence of melatonin at quantities from pharmacological to physiological doses were performed. The ototoxicity produced by gentamicin and tobramycin was maximal from days 3 to 5 post-treatment, returning to normal values in 2 wk. When melatonin was present, the recovery was at day 5 post-treatment, independently of the means of administration of the pineal product. The antibiograms showed that melatonin had no effect on the antibiotic capacity. It is concluded that the ototoxicity caused by gentamicin and tobramycin is ameliorated by melatonin and that the pineal hormone does not interfere with the antibiotic capacity of these antibiotics. PMID:10626598

  11. Long-term daily melatonin infusion induces a large increase in N-acetyltransferase activity, hydroxyindole-O-methyltransferase activity, and melatonin content in the Harderian gland and eye of pinealectomized male Siberian hamsters (Phodopus sungorus).

    PubMed

    Djeridane, Y; Pitrosky, B; Vivien-Roels, B; Simonneaux, V; Kirsch, R; Pévet, P

    2000-09-01

    The effects of long-term daily melatonin infusions on the melatonin synthetic pathway in the Harderian glands and eyes of male Siberian hamsters were studied. Hamsters were pinealectomized (PX) and infused daily for 8 hr with either melatonin (6 microg/hr) or vehicle for 7 days in short photoperiod (SP, 10L:14D), followed by 14 wk in either SP (SP group) or in constant darkness (DD group). After the infusion period (15 wk), the infusion was stopped and animals were transferred into SP for 3 wk. The hamsters were then killed at midday or midnight. Exogenous melatonin infusion caused an increase in the Harderian gland weight, which was still evident 3 wk after the end of the treatment. In addition, exogenous melatonin increased endogenous melatonin concentrations (4-fold) and hydroxyindole-O-methyltransferase (HIOMT) activity (2-fold). N-acetyltransferase (NAT) activity, however, was not increased, and no day/night difference in melatonin content and HIOMT activity was observed in the Harderian glands. In the eye, melatonin infusions significantly increased day and night-time melatonin levels (up to 3-fold) and both NAT and HIOMT activities (up to 3.5-fold). This effect of melatonin treatment was observed in both SP and DD groups. These observations demonstrate that exogenously-infused melatonin at relatively high doses activates the synthesis of endogenous melatonin in the Harderian gland and eye of the Siberian hamster. Circulating levels of melatonin were also markedly increased, indicating that in these conditions melatonin may be released from extra-pineal sites.

  12. A reproductive phase-dependent effect of dietary L-tryptophan on pineal gland and gonad of a nocturnal bird, Indian spotted owlet Athene brama.

    PubMed

    Guchhait, P; Haldar, C

    2001-01-01

    Unlike other temperate owls, Indian spotted owlet Athene brama possesses a well-developed pineal gland that secrets moderate amount of hydroxy- (serotonin) and methoxy- (melatonin) indoles in circulation. However, in this study, we have reported the response of this endocrine gland to exogenous L-Tryptophan (precursor of the above indoles), and also its effect on gonads of this nocturnal bird. During breeding phase or pineal inactive phase (March), oral treatment of L-Trp (0.5 mg/100 g Bwt/day) significantly increased the pineal gland wt and plasma melatonin (MEL) level, while decreased the gonadal wt and plasma sex steroids levels (estradiol and progesterone in female and testosterone in male). Interestingly, during reproductively quiescent phase or pineal active phase (August), similar amount of L-Trp significantly decreased the plasma MEL level, while increased the above sex steroid levels in plasma. Finally, the results show a clear reproductive phase-dependent inverse effect of L-Trp on pineal gland and gonads for both sexes of the spotted owlets, and suggest that the therapeutic use of this amino acid would be a great advantage for controlling the reproduction of these economically important birds.

  13. Retino-hypothalamic-pineal hypothesis in the pathophysiology of primary headaches.

    PubMed

    Deshmukh, Vinod D

    2006-01-01

    Primary headaches include migraine, tension, cluster headaches, paroxysmal hemicrania and miscellaneous headaches unassociated with structural lesions. A putative role of the retino-hypothalamic-pineal (RHP) axis in the pathophysiology of primary headaches is reviewed in terms of (1) retinal dysfunction, (2) hypothalamic dysfunction and human circadian desynchrony, (3) pineal melatonin dysfunction and (4) rostral limbic dysfunction mediating the human stress response. Unified RHP hypothesis is proposed, suggesting that an acute, periodic or chronic, circadian desynchrony and dysfunction of the whole or part of the RHP axis is implicated in the pathophysiology of primary headaches. Supportive evidence for the RHP hypothesis, including recent PET studies showing changes in dorsal pons, hypothalamus and rostral limbic structures, is presented.

  14. Melatonin exerts by an autocrine loop antiproliferative effects in cholangiocarcinoma: its synthesis is reduced favoring cholangiocarcinoma growth.

    PubMed

    Han, Yuyan; Demorrow, Sharon; Invernizzi, Pietro; Jing, Qing; Glaser, Shannon; Renzi, Anastasia; Meng, Fanyin; Venter, Julie; Bernuzzi, Francesca; White, Mellanie; Francis, Heather; Lleo, Ana; Marzioni, Marco; Onori, Paolo; Alvaro, Domenico; Torzilli, Guido; Gaudio, Eugenio; Alpini, Gianfranco

    2011-10-01

    Cholangiocarcinoma (CCA) is a devastating biliary cancer. Melatonin is synthesized in the pineal gland and peripheral organs from serotonin by two enzymes, serotonin N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT). Cholangiocytes secrete neuroendocrine factors, including serotonin-regulating CCA growth by autocrine mechanisms. Melatonin exerts its effects by interaction with melatonin receptor type 1A/1B (MT1/MT2) receptors. We propose that 1) in CCA, there is decreased expression of AANAT and ASMT and secretion of melatonin, changes that stimulate CCA growth; and 2) in vitro overexpression of AANAT decreases CCA growth. We evaluated the 1) expression of AANAT, ASMT, melatonin, and MT1/MT2 in human nonmalignant and CCA lines and control and CCA biopsy samples; 2) melatonin levels in nonmalignant and CCA lines, and bile and serum from controls and patients with intrahepatic CCA; 3) effect of melatonin on the growth and expression of AANAT/ASMT and MT1/MT2 in CCA lines implanted into nude mice; and 4) effect of AANAT overexpression on the proliferation, apoptosis, and expression of MT1/MT2 in Mz-ChA-1 cells. The expression of AANAT, ASMT, and melatonin decreased, whereas MT1/MT2 expression increased in CCA lines and biopsy samples. Melatonin secretion decreased in the supernatant of CCA lines and bile of CCA patients. Melatonin decreased xenograft CCA tumor growth in nude mice by increased AANAT/ASMT and melatonin, along with reduced MT1/MT2 expression. Overexpression of AANAT in Mz-ChA-1 cells inhibited proliferation and MT1/MT2 expression and increased apoptosis. There is dysregulation of the AANAT/ASMT/melatoninmelatonin receptor axis in CCA, which inhibited melatonin secretion and subsequently enhanced CCA growth.

  15. Continuous Melatonin Attenuates the Regressing Activities of Short Photoperiod in Male Golden Hamsters

    PubMed Central

    Choi, Donchan

    2013-01-01

    Golden hamsters reproduce in a limited time of a year. Their sexual activities are active in summer but inactive in winter during which day length does not exceed night time and environmental conditions are severe to them. The reproductive activities are determined by the length of light in a day (photoperiod). Melatonin is synthesized and secreted only at night time from the pineal gland. Duration of elevated melatonin is longer in winter than summer, resulting in gonadal regression. The present study aimed at the influences of continuous melatonin treatments impinging on the gonadal function in male golden hamsters. Animals received empty or melatonin-filled capsules for 10 weeks. They were divided into long photoperiod (LP) and short photoperiod (SP). All the animals maintained in LP (either empty or melatonin-filled capsules) showed large testes, implying that melatonin had no effects on testicular functions. Animals housed in SP displayed completely regressed testes. But animals kept in SP and implanted with melatonin capsules exhibited blockage of full regression by SP. These results suggest that constant release of melatonin prohibits the regressing influence of SP. PMID:25949127

  16. Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular Degeneration

    PubMed Central

    Reiter, Russel J.; Kaarniranta, Kai

    2016-01-01

    Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a circadian fashion, but it is produced in many other organs, including the retina, which seems to be especially important as the eye is a primary recipient of circadian signals. Melatonin displays strong antioxidative properties, which predispose it to play a protective role in many human pathologies associated with oxidative stress, including premature aging and degenerative disease. Therefore, melatonin may play a role in age-related macular degeneration (AMD), a disease affecting photoreceptors, and retinal pigment epithelium (RPE) with an established role of oxidative stress in its pathogenesis. Several studies have shown that melatonin could exert the protective effect against damage to RPE cells evoked by reactive oxygen species (ROS), but it has also been reported to increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels; thus, melatonin may prevent mitochondrial damage in AMD. The retina contains telomerase, an enzyme implicated in maintaining the length of telomeres, and oxidative stress inhibits telomere synthesis, while melatonin overcomes this effect. These features support considering melatonin as a preventive and therapeutic agent in the treatment of AMD.

  17. Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular Degeneration

    PubMed Central

    Reiter, Russel J.; Kaarniranta, Kai

    2016-01-01

    Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a circadian fashion, but it is produced in many other organs, including the retina, which seems to be especially important as the eye is a primary recipient of circadian signals. Melatonin displays strong antioxidative properties, which predispose it to play a protective role in many human pathologies associated with oxidative stress, including premature aging and degenerative disease. Therefore, melatonin may play a role in age-related macular degeneration (AMD), a disease affecting photoreceptors, and retinal pigment epithelium (RPE) with an established role of oxidative stress in its pathogenesis. Several studies have shown that melatonin could exert the protective effect against damage to RPE cells evoked by reactive oxygen species (ROS), but it has also been reported to increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels; thus, melatonin may prevent mitochondrial damage in AMD. The retina contains telomerase, an enzyme implicated in maintaining the length of telomeres, and oxidative stress inhibits telomere synthesis, while melatonin overcomes this effect. These features support considering melatonin as a preventive and therapeutic agent in the treatment of AMD. PMID:27688828

  18. Pineal and gonadal influences on ultradian locomotor rhythms of male Siberian hamsters

    PubMed Central

    Prendergast, Brian J.; Cable, Erin J.; Cisse, Yasmine M.; Stevenson, Tyler J.; Zucker, Irving

    2013-01-01

    The extent to which changes in ultradian and circadian rhythms (URs and CRs) reflect seasonal variations in pineal melatonin secretion was assessed in male Siberian hamsters transferred from long to short day lengths. The period of the locomotor activity UR increased from 2.5 h in long days to 4.5 h in short day lengths, but this and most other features of the short-day ultradian phenotype were unaffected by pinealectomy; only the short-day increase in UR amplitude was counteracted by pineal extirpation. Virtually all UR components were unaffected by gonadectomy or replacement testosterone or estradiol treatment; changes in testicular hormone secretion appear insufficient to account for seasonal fluctuation in URs. Pinealectomy did not affect activity onsets and offsets or phase angles of CR entrainment in short and long day lengths; the duration of nocturnal activity was equivalently longer in short than long days in both pinealectomized and pineal-intact hamsters. CR robustness of pinealectomized hamsters in short days was intermediate between values of long-day and short-day sham-pinealectomized males. Hourly nocturnal locomotor activity was markedly reduced in SD, and this effect was completely reversed by PINx. We conclude that seasonal transitions in UR and CR waveforms controlled by day length are mediated primarily by melatonin-independent mechanisms, with lesser contributions from melatonin-dependent processes. Most seasonal changes in ultradian and circadian rhythms in males of this species are not influenced by gonadal hormones. URs may allow animals to respond appropriately to changing environmental contingencies. In winter reduced activity combined with temporal restructuring of activity to include longer intervals of rest may be adaptive in maintaining body temperature at lower values and down-regulating energy expenditure when above ground temperatures are extremely low. PMID:23142326

  19. A test of the coincidence and duration models of melatonin action in Siberian hamsters: the effects of 1-hr melatonin infusions on testicular development in intact and pinealectomized prepubertal Phodopus sungorus.

    PubMed

    Gündüz, B; Stetson, M H

    2001-03-01

    The pineal hormone melatonin is known to play an important role in mediating photoperiodic messages to the reproductive system in seasonal breeding animals. Our goal was to test, in a single experimental paradigm, two hypotheses that have been forwarded to describe how the circadian rhythm of pineal melatonin transmits photoperiodic information to the reproductive system: 1) induction, i.e., a short-day effect, occurs when secreted melatonin and a circadian rhythm of sensitivity to melatonin coincide in time; 2) induction occurs following exposure to elevated circulating melatonin levels for a prescribed duration. In order to determine the relative validity of these hypotheses, we investigated the testicular maturation response to 1-hr daily infusions of 10, 25, and 50 ng of melatonin in pinealectomized intact and prepubertal Siberian hamsters (Phodopus sungorus). Animals received, beginning on day 15 of life, programmed subcutaneous infusions of melatonin or vehicle at one of five time points (19:00-20:00, 20:00-21:00, 21:00-22:00, 24:00-01:00, and 03:00-04:00 hr) for 15 days. In animals gestated and raised in a long photoperiod (LD16:8 = 16L, where L is the duration of light in hours, and D that of dark), melatonin infusion right after lights off (20:00-21:00 hr) significantly retarded gonadal maturation; this dose was ineffective at other times tested. Doses of 10 and 25 ng melatonin were ineffective at all time points. Identical results were obtained in prepubertal hamsters gestated in a short photoperiod (LD10:14 = 10L) and raised in 16L; these results were independent of the presence or absence of the pineal gland. In animals gestated and raised in 10L, melatonin infusions failed to suppress testicular development beyond that induced by the photoperiod; testicular development was maximally suppressed in all groups. The results of these investigations are best explained under the experimental conditions employed here: 1) the photoperiodic gonadal response in

  20. Characterization of binding sites for [3H]-DTG, a selective sigma receptor ligand, in the sheep pineal gland.

    PubMed

    Abreu, P; Sugden, D

    1990-09-14

    Specific binding sites for [3H]-1,3 di-ortho-tolylguanidine ([3H]-DTG), a selective radiolabeled sigma receptor ligand, were detected and characterized in sheep pineal gland membranes. The binding of [3H]-DTG to sheep pineal membranes was rapid and reversible with a rate constant for association (K+1) at 25 degrees C of 0.0052 nM-1.min-1 and rate constant for dissociation (K-1) 0.0515 min-1, giving a Kd (K-1/K+1) of 9.9 nM. Saturation studies demonstrated that [3H]-DTG binds to a single class of sites with an affinity constant (Kd) of 27 +/- 3.4 nM, and a total binding capacity (Bmax) of 1.39 +/- 0.03 pmol/mg protein. Competition experiments showed that the relative order of potency of compounds for inhibition of [3H]-DTG binding to sheep pineal membranes was as follows: trifluoperazine = DTG greater than haloperidol greater than pentazocine greater than (+)-3-PPP greater than (+/-)SKF 10,047. Some steroids (testosterone, progesterone, deoxycorticosterone) previously reported to bind to the sigma site in brain membranes were very weak inhibitors of [3H]-DTG binding in the present study. The results indicate that [3H]-DTG binding sites having the characteristics of sigma receptors are present in sheep pineal gland. The physiological importance of these sites in regulating the synthesis of the pineal hormone melatonin awaits further study. PMID:2169739

  1. Melatonin in humans: Possible involvement in SIDS, and use in contraceptives

    NASA Technical Reports Server (NTRS)

    Wurtman, Richard J.; Lynch, Harry J.; Sturner, William Q.

    1991-01-01

    Relatively few tools exist for assessing the possible involvement of melatonin in normal or abnormal physiologlcal and behavioral states. One cannot perform the classic ablation experiment of endocrinologists by cavalierly removing the human's pineal, nor derive the same effect pharmacologically by administering a drug which blocks the actions of the indole on its receptors (because no such drugs, demonstrated to work in humans, exist). About all that can be done is to administer the melatonin and see what happens, or measure its levels in a body fluid and determine whether its temporal patterns track those of the physiological or behavioral variable being examined. The clinical state of Sudden Infant Death Syndrome (SIDS) which apparently is associated with abnormalities in melatonin concentrations within body fluids obtained at autopsy is described. New data which suggest that exogenous melatonin has sufficient antigonadal potency to allow it to replace estrogen and, acting in combination with norethisterone, serve as a useful contraceptive agent is summarized.

  2. Interactions of melatonin and serotonin with lactoperoxidase enzyme.

    PubMed

    Şişecioğlu, Melda; Çankaya, Murat; Gülçin, İlhami; Özdemir, Hasan

    2010-12-01

    Melatonin is the chief secretory product of the pineal gland and is synthesized enzymatically from serotonin. These indoleamine derivatives play an important role in the prevention of oxidative damage. Lactoperoxidase (LPO; EC 1.11.1.7) was purified from bovine milk with three purification steps: Amberlite CG-50 resin, CM-Sephadex C-50 ion-exchange, and Sephadex G-100 gel filtration chromatography, respectively. LPO was purified with a yield of 21.6%, a specific activity of 34.0 EU/mg protein, and 14.7-fold purification. To determine the enzyme purity, SDS-PAGE was performed and a single band was observed. The R(z) (A(412)/A(280)) value for LPO was 0.9. The effect of melatonin and serotonin on lactoperoxidase was determined using ABTS as chromogenic substrate. The half-maximal inhibitory concentration (IC(50)) values for melatonin and serotonin were found to be 1.46 and 1.29 μM, respectively. Also, the inhibition constants (K(i)) for melatonin and serotonin were 0.82 ± 0.28 and 0.26 ± 0.04 μM, respectively. Both melatonin and serotonin were found to be competitive inhibitors.

  3. Effects of melatonin and prolactin in reproduction: review of literature.

    PubMed

    Tenorio, Fernanda das Chagas Angelo Mendes; Simões, Manuel de Jesus; Teixeira, Valéria Wanderley; Teixeira, Álvaro Aguiar Coelho

    2015-01-01

    The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.

  4. Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal gland.

    PubMed

    Stehle, J H; Foulkes, N S; Molina, C A; Simonneaux, V; Pévet, P; Sassone-Corsi, P

    1993-09-23

    Transcription factor CREM appears to play a key physiological and developmental role within the hypothalamic-pituitary-gonadal axis. This axis is modulated by the pineal hormone melatonin, whose production is in turn driven by the endogenous clock. There is striking circadian fluctuation of a novel CREM isoform, ICER, which is expressed at high levels during the night. ICER is generated from an alternative, intronic promoter and functions as a powerful repressor of cyclic AMP-induced transcription. Rhythmic adrenergic signals originated by the clock direct ICER expression by stimulation of the cAMP signal transduction pathway.

  5. The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes.

    PubMed

    Leonardo-Mendonça, Roberto C; Martinez-Nicolas, Antonio; de Teresa Galván, Carlos; Ocaña-Wilhelmi, Javier; Rusanova, Iryna; Guerra-Hernández, Eduardo; Escames, Germaine; Acuña-Castroviejo, Darío

    2015-01-01

    Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100 mg day(-1) of melatonin or placebo 30 min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00 h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep-wake cycle, improving sleep efficiency. PMID:26361788

  6. Melatonin: both master clock output and internal time-giver in the circadian clocks network.

    PubMed

    Pevet, Paul; Challet, Etienne

    2011-12-01

    Daily rhythms in physiological and behavioral processes are controlled by a network of circadian clocks, reset by inputs and delivering circadian signals to the brain and peripheral organs. In mammals, at the top of the network is a master clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus, mainly reset by ambient light. The nocturnal synthesis and release of melatonin by the pineal gland are tightly controlled by the SCN clock and inhibited by light exposure. Several roles of melatonin in the circadian system have been identified. As a major hormonal output, melatonin distributes temporal cues generated by the SCN to the multitude of tissue targets expressing melatonin receptors. In some target structures, like the Pars tuberalis of the adenohypophysis, these melatonin signals can drive daily rhythmicity that would otherwise be lacking. In other target structures, melatonin signals are used for the synchronization (i.e., adjustment of the timing of existing oscillations) of peripheral oscillators, such as the fetal adrenal gland. Due to the expression of melatonin receptors in the SCN, endogenous melatonin is also able to feedback onto the master clock, although its physiological significance needs further characterization. Of note, pharmacological treatment with exogenous melatonin can synchronize the SCN clock. From a clinical point of view, provided that the subject is not exposed to light at night, the daily profile of circulating melatonin provides a reliable estimate of the timing of the human SCN. During the past decade, a number of melatonin agonists have been developed for treating circadian, psychiatric and sleep disorders. These drugs may target the SCN for improving circadian timing or act indirectly at some downstream level of the circadian network to restore proper internal synchronization.

  7. Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease

    PubMed Central

    Nombela, Cristina; Vuono, Romina; Jones, P. Simon; Fisher, Kate; Burn, David J.; Brooks, David J.; Reddy, Akhilesh B.; Rowe, James B.; Barker, Roger A.

    2016-01-01

    ABSTRACT Background Recent studies have suggested that melatonin—a hormone produced by the pineal gland under circadian control—contributes to PD‐related sleep dysfunction. We hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. We compared hypothalamic volumes in PD patients with matched controls and determined whether volume loss correlated with reduced melatonin output in the PD group. Methods A total of 12 PD patients and 12 matched controls underwent magnetic resonance imaging to determine hypothalamic volume. In addition, PD patients underwent 24‐hour blood sampling in a controlled environment to determine serum melatonin concentrations using enzyme‐linked immunosorbent assays. Results PD patients had significantly reduced hypothalamic gray matter volume when compared with matched controls. Melatonin levels were significantly associated with hypothalamic gray matter volume and disease severity in PD patients. Conclusion Melatonin levels are associated with hypothalamic gray matter volume loss and disease severity in PD patients. This provides anatomical and physiological support for an intrinsic sleep and circadian phenotype in PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:26971528

  8. Melatonin action in a midbrain vocal-acoustic network

    PubMed Central

    Feng, Ni Y.; Bass, Andrew H.

    2014-01-01

    Melatonin is a well-documented time-keeping hormone that can entrain an individual's physiology and behavior to the day–night cycle, though surprisingly little is known about its influence on the neural basis of social behavior, including vocalization. Male midshipman fish (Porichthys notatus) produce several call types distinguishable by duration and by daily and seasonal cycles in their production. We investigated melatonin's influence on the known nocturnal- and breeding season-dependent increase in excitability of the midshipman's vocal network (VN) that directly patterns natural calls. VN output is readily recorded from the vocal nerve as a ‘fictive call’. Five days of constant light significantly increased stimulus threshold levels for calls electrically evoked from vocally active sites in the medial midbrain, supporting previous findings that light suppresses VN excitability, while 2-iodomelatonin (2-IMel; a melatonin analog) implantation decreased threshold. 2-IMel also increased fictive call duration evoked from medial sites as well as lateral midbrain sites that produced several-fold longer calls irrespective of photoregime or drug treatment. When stimulus intensity was incrementally increased, 2-IMel increased duration only at lateral sites, suggesting that melatonin action is stronger in the lateral midbrain. For animals receiving 5 days of constant darkness, known to increase VN excitability, systemic injections of either of two mammalian melatonin receptor antagonists increased threshold and decreased duration for calls evoked from medial sites. Our results demonstrate melatonin modulation of VN excitability and suggest that social context-dependent call types differing in duration may be determined by neuro-hormonal action within specific regions of a midbrain vocal-acoustic network. PMID:24265429

  9. Melatonin improves spermatogonial stem cells transplantation efficiency in azoospermic mice

    PubMed Central

    Gholami, Mohammadreza; Saki, Ghasem; Hemadi, Masoud; Khodadadi, Ali; Mohammadi-asl, Javad

    2014-01-01

    Objective(s): Transplantation quality improvement and reduction of cellular damage are important goals that are now considered by researchers. Melatonin is secreted from the pineal gland and some organs such as testes. According to beneficial effects of melatonin (such as its antioxidant and antiapoptotic properties), researchers have proposed that the use of melatonin may improve transplantation quality. The aim of this study was to investigate the effects of melatonin on the spermatogonial stem cells transplantation in the azoospermic mice. Materials and Methods: The testes of the BALB/c mice pups (6-day-old) after vitrified-thawed, were digested with enzymes (collagenase, DNaseΙ, trypsin-EDTA) to disperse the cells. The SSCs, type A, were isolated from the rest of testicular cells by MACS. Spermatogonial stem cells were labeled with PKH26 fluorescent kit. Labeled spermatogonial stem cells were transplanted into the testes of infertile mice (busulfan 40 mg/kg). The mice died two months after transplantation and the efficiency of spermatogenesis was investigated. TNP2 and hematoxyline-eosin staining were used to detect the efficiency of cell transplantation. Results: TNP2 were detected in the samples that received melatonin and spermatogonial stem cells transplantation, simultaneously. TNP2 was not detectable in the transplant recipient mice that received placebo for 10 weeks (control group). According to hematoxyline-eosin staining, melatonin improved structure of testes. Conclusion: Administration of melatonin (20 mg/kg) simultaneously with transplantation of spermatogonial stem cells in azoospermia mouse testis increases the efficiency of transplantation and improves structural properties of the testes tissue. PMID:24711891

  10. Melatonin in Glycyrrhiza uralensis: response of plant roots to spectral quality of light and UV-B radiation.

    PubMed

    Afreen, F; Zobayed, S M A; Kozai, T

    2006-09-01

    Melatonin (N-acetyl-5-methoxytryptamine) is known to be synthesized and secreted by the pineal gland in vertebrates. Evidence for the occurrence of melatonin in the roots of Glycyrrhiza uralensis plants and the response of this plant to the spectral quality of light including red, blue and white light (control) and UV-B radiation (280-315 nm) for the synthesis of melatonin were investigated. Melatonin was extracted and quantified in seed, root, leaf and stem tissues and results revealed that the root tissues contained the highest concentration of melatonin; melatonin concentrations also increased with plant development. After 3 months of growth under red, blue and white fluorescent lamps, the melatonin concentrations were highest in red light exposed plants and varied depending on the wavelength of light spectrum in the following order red > blue > or = white light. Interestingly, in a more mature plant (6 months) melatonin concentration was increased considerably; the increments in concentration were X4, X5 and X3 in 6-month-old red, blue and white light exposed (control) plants, respectively. The difference in melatonin concentrations between blue and white light exposed (control) plants was not significant. The concentration of melatonin quantified in the root tissues was highest in the plants exposed to high intensity UV-B radiation for 3 days followed by low intensity UV-B radiation for 15 days. The reduction of melatonin under longer periods of UV-B exposure indicates that melatonin synthesis may be related to the integrated (intensity and duration) value of UV-B irradiation. Melatonin in G. uralensis plant is presumably for protection against oxidative damage caused as a response to UV irradiation.

  11. Melatonin and its precursor, L-tryptophan: influence on pancreatic amylase secretion in vivo and in vitro.

    PubMed

    Jaworek, Jolanta; Nawrot, Katarzyna; Konturek, Stanisław J; Leja-Szpak, Anna; Thor, Piotr; Pawlik, Wiesław W

    2004-04-01

    Melatonin, considered as a main pineal product, may be also synthetized in the gastrointestinal tract from L-tryptophan. Melatonin has been recently shown to affect insulin release and its receptors have been characterized in the pancreas however, the effects of melatonin on the pancreatic enzyme secretion have not been examined. The aim of this study was to investigate the effects of melatonin or L-tryptophan on amylase secretion in vivo in anaesthetized rats with pancreato-biliary fistulas, and in vitro using isolated pancreatic acini. Melatonin (1, 5 or 25 mg/kg) or L-tryptophan (10, 50 or 250 mg/kg) given to the rats as a intraperitoneal (i.p.) bolus injection produced significant and dose-dependent increases in pancreatic amylase secretion under basal conditions or following stimulation of enzyme secretion by diversion of bile-pancreatic juice. This was accompanied by a dose-dependent rise in melatonin plasma level. Stimulation of pancreatic enzyme secretion caused by melatonin or L-tryptophan was completely abolished by vagotomy, deactivation of sensory nerves with capsaicin or pretreatment with CCK1 receptor antagonists (tarazepide or L-364,718). Pretreatment with luzindole, an antagonist of melatonin MT(2) receptor failed to affect melatonin- or L-tryptophan-induced amylase secretion. Administration of melatonin (1, 5 or 25 mg/kg i.p.) or L-tryptophan (10, 50 or 250 mg/kg i.p.) to the rats resulted in the dose-dependent increase of cholecystokinin (CCK) plasma immunoreactivity. Enzyme secretion from isolated pancreatic acini was not significantly affected by melatonin or L-tryptophan used at doses of 10(-8) -10(-5) M. We conclude that exogenous melatonin, as well as that produced endogenously from L-tryptophan, stimulates pancreatic enzyme secretion in vivo while increasing CCK release. Stimulatory effect of melatonin or L-tryptophan on the exocrine pancreas involves vagal sensory nerves and the CCK release by these substances.

  12. Gingival, Plasma and Salivary Levels of Melatonin in Periodontally Healthy Individuals and Chronic Periodontitis Patients: A Pilot Study

    PubMed Central

    Balaji, Thodur Madapusi; Vasanthi, Hannah Rachel

    2015-01-01

    Introduction: Periodontal disease is an inflammatory condition affecting tooth supporting structures in which dysregulated immune response and oxidative stress mediate tissue destruction. Melatonin, the pineal gland hormone is a regulator of circadian rhythm, an antioxidant and an immunomodulator. Previous studies have shown lowered melatonin levels in saliva, plasma and gingival crevicular fluid (GCF) of patients with periodontal disease. Till date no study has assessed the melatonin levels in gingival tissues. Materials and Methods: Five healthy individuals and 15 chronic periodontitis patients were recruited for this pilot study. 5ml of whole saliva, 2 ml peripheral blood and gingival tissue samples were obtained from each individual at 8.00 am in fasting state. Melatonin assay was performed with a commercially available ELISA kit. Statistical analysis was done to assess the difference in mean melatonin levels among the groups. Results: No statistically significant difference was found in mean melatonin levels between healthy individuals and chronic periodontitis patients in saliva (p=.266) and plasma (p=.933) samples, whereas in gingival tissue samples (p=.015), the melatonin levels were significantly lowered in chronic periodontitis patients compared to healthy individuals. Conclusion: This study demonstrates the presence of melatonin in gingival tissue. Furthermore, melatonin levels are lowered in gingival tissues of chronic periodontitis patients. PMID:25954699

  13. Pineal-dependent and -independent effects of photoperiod on immune function in Siberian hamsters (Phodopus sungorus)

    PubMed Central

    Wen, Jarvi C.; Dhabhar, Firdaus S.; Prendergast, Brian J.

    2010-01-01

    Siberian hamsters (Phodopus sungorus) exhibit reproductive and immunological responses to photoperiod. Short (<10-h light/day) days induce gonadal atrophy, increase leukocyte concentrations, and attenuate thermoregulatory and behavioral responses to infection. Whereas hamster reproductive responses to photoperiod are dependent on pineal melatonin secretion, the role of the pineal in short-day induced changes in immune function is not fully understood. To examine this, adult hamsters were pinealectomized (PINx) or sham-PINx, and transferred to short days (9-h light/day; SD) or kept in their natal long-day (15-h light/day; LD) photoperiod. Intact and PINx hamsters housed in LD maintained large testes over the next 12 weeks; sham-PINx hamsters exhibited gonadal regression in SD, and PINx abolished this effect. Among pineal-intact hamsters, blood samples revealed increases in leukocyte, lymphocyte, CD62L+ lymphocyte, and T cell counts in SD relative to LD; PINx did not affect leukocyte numbers in LD hamsters, but abolished the SD increase in these measures. Hamsters were then treated with bacterial lipopolysaccharide (LPS), which induced thermoregulatory (fever), behavioral (anorexia, reductions in nest building), and somatic (weight loss) sickness responses in all groups. Among pineal-intact hamsters, febrile and behavioral responses to LPS were attenuated in SD relative to LD. PINx did not affect sickness responses to LPS in LD hamsters, but abolished the ameliorating effects of SD on behavioral responses to LPS. Surprisingly, PINx failed to abolish the effect of SD on fever. In common with the reproductive system, PINx induces the LD phenotype in most aspects of the immune system. The pineal gland is required for photoperiodic regulation of circulating leukocytes and neural-immune interactions that mediate select aspects of sickness behaviors. PMID:17022983

  14. Photoperiod: Its importance as an impeller of pineal and seasonal reproductive rhythms

    NASA Astrophysics Data System (ADS)

    Reiter, R. J.

    1980-03-01

    A number of long day breeding rodents depend on seasonal changes in photoperiodic length to synchronize their breeding seasons with the appropriate time of the year. These relationships are particularly conspicuous in the Syrian hamster where day length is vitally important in determining periods of sexual activity and inactivity. The organ in the body whose activity is most closely attuned to the photoperiodic environment is the pineal gland. During periods of darkness the biochemical and secretory activity of the pineal is enhanced with the resultant production of antigonadotrophic principles which are strongly suppressive to reproductive physiology. In this manner, decreasing day lengths of the fall are involved with suppressing sexual capability in male and female hamsters. Throughout the winter months darkness (because of the shorter day lengths and the fact that hamsters remain underground in lightless burrows) holds the gonads in an atrophic condition and thereby prevents hamsters from breeding. As spring approaches the neuroendocrine reproductive axis becomes refractory to the inhibitory effects of darkness and the pineal gland and, as a consequence, the gonads recrudesce allowing the animals to successfully reproduce. The long days of the spring and summer serve to interrupt the refractory period so that when winter approaches shortening day lengths will again, by way of the pineal gland, induce gonadalinvolution. In this scheme both light and darkness are critically important in synchronizing the phases of the annual reproductive cycle of the hamster with the appropriate season of the year. Melatonin may be the pineal hormone which mediates the effects of darkness on reproductive physiology.

  15. Historical and cultural aspects of the pineal gland: comparison between the theories provided by Spiritism in the 1940s and the current scientific evidence.

    PubMed

    Lucchetti, Giancarlo; Daher, Jorge C; Iandoli, Decio; Gonçalves, Juliane P B; Lucchetti, Alessandra L G

    2013-01-01

    Significance has been attached to the pineal gland in numerous different cultures and beliefs. One religion that has advanced the role of the pineal gland is Spiritism. The objective of the present study was to compile information on the pineal gland drawing on the books of Francisco Cândido Xavier written through psychography and to carry out a critical analysis of their scientific bases by comparing against evidence in the current scientific literature. A systematic search using the terms "pineal gland" and "epiphysis" was conducted of 12 works allegedly dictated by the spirit "André Luiz". All information on the pineal having potential correlation with the field of medicine and current studies was included. Specialists in the area were recruited to compile the information and draw parallels with the scientific literature. The themes related to the pineal gland were: mental health, reproductive function, endocrinology, relationship with physical activity, spiritual connection, criticism of the theory that the organ exerts no function, and description of a hormone secreted by the gland (reference alluding to melatonin, isolated 13 years later). The historical background for each theme was outlined, together with the theories present in the Spiritist books and in the relevant scientific literature. The present article provides an analysis of the knowledge the scientific community can acquire from the history of humanity and from science itself. The process of formulating hypotheses and scientific theories can benefit by drawing on the cultural aspects of civilization, taking into account so-called non-traditional reports and theories.

  16. Effect of melatonin on 24-hour rhythms of ornithine decarboxylase activity and norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged rats.

    PubMed

    Cardinali, D P; Brusco, L I; García Bonacho, M; Esquifìno, A I

    1998-05-01

    Young (50 days old) and old (18 months old) Sprague-Dawley rats were injected with mycobacterial Freund's adjuvant to produce an inflammatory disease of the joints and were studied the day before, and on days 6, 12 and 18 after injection. At every postinjection interval examined, old rats had significantly lower circadian amplitudes of pineal melatonin content. On day 18 of arthritis development, decreased levels of pineal melatonin were also seen in young rats. A second study, carried out 18 days after the injection of Freund's complete adjuvant and after 17 daily injections of 10 or 100 microg of melatonin in the evening, indicated that melatonin treatment restored the inflammatory response in old rats (assessed plethysmographically in hind paws) to the level found in young animals. In young rats, an inflammation-promoting effect of 100 microg melatonin could be demonstrated. As a consequence of the immune reaction, submaxillary lymph node and splenic ornithine decarboxylase activity (an index of lymph cell proliferation) augmented significantly, with acrophases of 24-hour rhythms in the afternoon for lymph nodes or in the morning for spleen. Mesor and amplitude of ornithine decarboxylase rhythm were lowest in old rats, while melatonin injection generally augmented its amplitude. Lymph node and splenic tyrosine hydroxylase activity (a presynaptic adrenergic marker) reached maximal values during early night hours while maximal values of [3H]acetylcholine synthesis (a presynaptic cholinergic marker) occurred during the afternoon in lymph nodes. Amplitude and mesor of these rhythms were lowest in old rats, an effect generally counteracted by melatonin treatment. The results suggest that inflammation is accompanied by an age-dependent, significant depression of pineal melatonin synthesis during adjuvant-induced arthritis and a decreased amplitude of the circadian rhythm of immune cell proliferation and autonomic activity in lymph nodes and spleen. These effects are

  17. Nocturnal plasma melatonin and alpha-melanocyte stimulating hormone levels during exacerbation of multiple sclerosis.

    PubMed

    Sandyk, R; Awerbuch, G I

    1992-01-01

    The pineal gland has been implicated recently in the pathogenesis of multiple sclerosis (MS). To investigate this hypothesis further, we studied nocturnal plasma melatonin levels and the presence or absence of pineal calcification (PC) on CT scan in a cohort of 25 patients (5 men, 20 women; mean age: 41.1 years; SD = 11.1; range: 27-72) who were admitted to a hospital Neurology service for exacerbation of symptoms. Plasma alpha-melanocyte stimulating hormone (alpha-MSH) estimations were included in the study since there is evidence for a feedback inhibition between alpha-MSH and melatonin secretion. Abnormal melatonin levels were found in 13 patients (52.0%), 11 of whom had nocturnal levels which were below the daytime values (i.e., < 25 pg/ml). Although melatonin levels were unrelated to the patient's age and sex, there was a positive correlation with age of onset of symptoms (p < .0001) and an inverse correlation with the duration of illness (p < .05). PC was noted in 24 of 25 patients (96%) underscoring the pathogenetic relationship between MS and the pineal gland. Alpha-MSH levels were undetectable in 15 patients (60.0%), low in two patients (8.0%), normal in seven patients (28.0%), and elevated in one patient (4.0%). Collectively, abnormal alpha-MSH levels were found in over 70% of patients. These findings support the hypothesis that MS may be associated with pineal failure and suggest, furthermore, that alterations in the secretion of alpha-MSH also occur during exacerbation of symptoms. The relevance of these findings to the pathogenesis of MS are discussed. PMID:1305632

  18. Melatonin prevents apoptosis induced by 6-hydroxydopamine in neuronal cells: implications for Parkinson's disease.

    PubMed

    Mayo, J C; Sainz, R M; Uria, H; Antolin, I; Esteban, M M; Rodriguez, C

    1998-04-01

    It was recently reported that low doses of 6-hydroxydopamine (6-OHDA) induce apoptosis of naive (undifferentiated) and neuronal (differentiated) PC12 cells, and this system has been proposed as an adequate experimental model for the study of Parkinson's disease. The mechanism by which this neurotoxin damages cells is via the production of free radicals. Given that the neurohormone melatonin has been reported 1) to be a highly effective endogenous free radical scavenger, 2) to increase the mRNA levels and the activity of several antioxidant enzymes, and 3) to inhibit apoptosis in other tissues, we have studied the ability of melatonin to prevent the programmed cell death induced by 6-OHDA in PC12 cells. We found that melatonin prevents the apoptosis caused by 6-OHDA in naive and neuronal PC12 cells as estimated by 1) cell viability assays, 2) counting of the number of apoptotic cells, and 3) analysis and quantification of DNA fragmentation. Exploration of the mechanisms used by melatonin to reduce programmed cell death revealed that this chemical mediator prevents the 6-OHDA induced reduction of mRNAs for several antioxidant enzymes. The possibility that melatonin utilized additional mechanisms to prevent apoptosis of these cells is also discussed. Since this endogenous agent has no known side effects and readily crosses the blood-brain-barrier, we consider melatonin to have a high clinical potential in the treatment of Parkinson's disease and possibly other neurodegenerative diseases, although more research on the mechanisms is yet to be done.

  19. Analgesic, Anxiolytic and Anaesthetic Effects of Melatonin: New Potential Uses in Pediatrics

    PubMed Central

    Marseglia, Lucia; D’Angelo, Gabriella; Manti, Sara; Aversa, Salvatore; Arrigo, Teresa; Reiter, Russel J.; Gitto, Eloisa

    2015-01-01

    Exogenous melatonin is used in a number of situations, first and foremost in the treatment of sleep disorders and jet leg. However, the hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a drug that modulates effects of anesthetic agents, supporting its potential use at different stages during anesthetic procedures, in both adults and children. In light of these properties, melatonin has been administered to children undergoing diagnostic procedures requiring sedation or general anesthesia, such as magnetic resonance imaging, auditory brainstem response tests and electroencephalogram. Controversial data support the use of melatonin as anxiolytic and antinociceptive agents in pediatric patients undergoing surgery. The aim of this review was to evaluate available evidence relating to efficacy and safety of melatonin as an analgesic and as a sedative agent in children. Melatonin and its analogs may have a role in antinociceptive therapies and as an alternative to midazolam in premedication of adults and children, although its effectiveness is still controversial and available data are clearly incomplete. PMID:25569095

  20. Reduction of Melatonin Level in Patients with Type II Diabetes and Periodontal Diseases.

    PubMed

    Abdolsamadi, Hamidreza; Goodarzi, Mohammad Taghi; Ahmadi Motemayel, Fatemeh; Jazaeri, Mina; Feradmal, Javad; Zarabadi, Mahdiyeh; Hoseyni, Mostafa; Torkzaban, Parviz

    2014-01-01

    Background and aims. Melatonin is a circulating hormone that is mainly released from the pineal gland. It possesses antioxidant, free-radical scavenging, and immune-enhancing properties. A growing number of studies reveal a complex role for melatonin in influencing various diseases, including diabetes and periodontal diseases. The aim of this study was to examine the possible links between salivary melatonin levels and type II diabetes and periodontal diseases. Materials and methods. A total of 30 type II diabetic patients, 30 patients with periodontal diseases, 30 type II diabetic patients with periodontal disease and 30 age- and BMI-matched controls were studied. The periodontal status was evaluated by the Community Periodontal Index (CPI). Salivary melatonin levels were determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit. Results. The mean of salivary melatonin level was significantly lower in patients with either periodontitis or diabetes compared to healthy subjects (P < 0.05). Salivary melatonin concentration decreased in type II diabetic patients and periodontitis patients, and then decreased reaching the lowest levels in type II diabetic patients with periodontal disease. Conclusion. Based on the results of this study, it can probably be concluded that salivary level of melatonin has an important role in the pathogenesis of diabetes and periodontal diseases. It is also worth noting that this factor could probably be used as a pivotal biological marker in the diagnosis and possible treatment of these diseases, although further research is required to validate this hypothesis. PMID:25346835

  1. Relation between nocturnal melatonin profile and hormonal markers of puberty in humans.

    PubMed

    Cavallo, A; Richards, G E; Smith, E R

    1992-01-01

    We examined the relation between nocturnal melatonin and hormonal markers of puberty in 57 normal children and adolescents and 39 subjects with disorders of pubertal onset. Melatonin was measured in hourly blood samples drawn overnight by constant withdrawal. Basal 08.00 h plasma testosterone, estradiol and LH, and the peak LH response to LHRH administration were determined. There were no significant correlations between testosterone, estradiol, basal LH and peak LH and melatonin peak (r = -0.18, -0.22, -0.02, -0.12, respectively) or melatonin peak time (r = 0.12, -0.01, -0.02, 0.07 respectively). The results were not affected significantly by sex, diagnosis or age. A comparison of subjects grouped by peak LH < 15 U/l (most likely prepubertal; n = 40) and peak LH > 30 U/l (most likely pubertal; n = 34) showed no significant differences in melatonin peak (160.5 +/- 59.3 vs. 146.6 +/- 50.9 pg/ml; t = 1.09; p > 0.05) or melatonin peak time (1.8 +/- 1.7 vs. 2.5 +/- 1.7 h; t = -1.79; p > 0.05). Although a pineal-puberty relation cannot be excluded, the results do not support the hypothesis that melatonin restrains the hypothalamic-pituitary-gonadal axis during childhood.

  2. Reduction of Melatonin Level in Patients with Type II Diabetes and Periodontal Diseases

    PubMed Central

    Abdolsamadi, Hamidreza; Goodarzi, Mohammad Taghi; Ahmadi Motemayel, Fatemeh; Jazaeri, Mina; Feradmal, Javad; Zarabadi, Mahdiyeh; Hoseyni, Mostafa; Torkzaban, Parviz

    2014-01-01

    Background and aims. Melatonin is a circulating hormone that is mainly released from the pineal gland. It possesses antioxidant, free-radical scavenging, and immune-enhancing properties. A growing number of studies reveal a complex role for melatonin in influencing various diseases, including diabetes and periodontal diseases. The aim of this study was to examine the possible links between salivary melatonin levels and type II diabetes and periodontal diseases. Materials and methods. A total of 30 type II diabetic patients, 30 patients with periodontal diseases, 30 type II diabetic patients with periodontal disease and 30 age- and BMI-matched controls were studied. The periodontal status was evaluated by the Community Periodontal Index (CPI). Salivary melatonin levels were determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit. Results. The mean of salivary melatonin level was significantly lower in patients with either periodontitis or diabetes compared to healthy subjects (P < 0.05). Salivary melatonin concentration decreased in type II diabetic patients and periodontitis patients, and then decreased reaching the lowest levels in type II diabetic patients with periodontal disease. Conclusion. Based on the results of this study, it can probably be concluded that salivary level of melatonin has an important role in the pathogenesis of diabetes and periodontal diseases. It is also worth noting that this factor could probably be used as a pivotal biological marker in the diagnosis and possible treatment of these diseases, although further research is required to validate this hypothesis. PMID:25346835

  3. Melatonin Signaling Controls the Daily Rhythm in Blood Glucose Levels Independent of Peripheral Clocks.

    PubMed

    Owino, Sharon; Contreras-Alcantara, Susana; Baba, Kenkichi; Tosini, Gianluca

    2016-01-01

    Melatonin is rhythmically secreted by both the pineal gland and retina in a circadian fashion, with its peak synthesis occurring during the night. Once synthesized, melatonin exerts its effects by binding to two specific G-protein coupled receptors-melatonin receptor type 1(MT1) and melatonin receptor type 2(MT2). Recent studies suggest the involvement of MT1 and MT2 in the regulation of glucose homeostasis; however the ability of melatonin signaling to impart timing cues on glucose metabolism remains poorly understood. Here we report that the removal of MT1 or MT2 in mice abolishes the daily rhythm in blood glucose levels. Interestingly, removal of melatonin receptors produced small effects on the rhythmic expression patterns of clock genes within skeletal muscle, liver, and adipose tissue. Taken together, our data suggest that the loss of the daily rhythm in blood glucose observed in MT1(-/-) and MT2(-/-) mice does not occur as a consequence of 'disrupted' clocks within insulin sensitive tissues. Finally our results highlight a diurnal contribution of melatonin receptor signaling in the daily regulation of blood glucose levels.

  4. Effect of melatonin on total food intake and macronutrient choice in rats.

    PubMed

    Angers, K; Haddad, N; Selmaoui, B; Thibault, L

    2003-10-01

    Melatonin, a hormone secreted in a rhythmic manner over 24 h mainly by the pineal gland, is used to alleviate the symptoms of jetlag and treat sleeping problems. The objective of the present study was to examine the effects of a 7-h phase-shift from the natural peak of melatonin secretion on total food intake and macronutrient selection. Forty-eight adult Wistar rats of both sexes were divided in three dietary groups, each group offered a simultaneous and different choice of a carbohydrate- and a protein-rich diet. Macronutrient intakes following intraperitoneal administration of four doses of melatonin (3000, 6000, 10000 and 15000 pg/ml blood) at dark onset were examined. Melatonin increased short- (4 h postinjection) and long-term (12 h postinjection) nocturnal total food intake in both male and female rats, mainly with the two highest doses. This effect of melatonin was mainly due to a short-term increase of intake across all carbohydrate-rich diet preparations (dextrin/cornstarch, cornstarch, and sucrose/cornstarch) and across genders. This consistent effect of melatonin on the intake of carbohydrate-rich diets with contrasting sensory attributes rules out the possibility that melatonin acts on sensorymotor pathways, thus suggesting that melatonin's effect on food intake is controlled by the carbohydrate content of the diet. In contrast, melatonin could be affecting some sensory or motor processes peculiar to the ingestion of protein since it increased protein-rich diet intake inconsistently across the various preparations (casein, soy isolate, and egg protein) as well as genders. This evidence supports the view that melatonin acts as a time indicator, reinforcing the animals with a "night cue", and favors predominant carbohydrate intake normally occurring at the beginning of the activity period.

  5. Melatonin-dopamine interactions: from basic neurochemistry to a clinical setting.

    PubMed

    Zisapel, N

    2001-12-01

    To review the interaction between melatonin and the dopaminergic system in the hypothalamus and striatum and its potential clinical use in dopamine-related disorders in the central nervous system. Medline-based search on melatonin-dopamine interactions in mammals. Melatonin. the hormone produced by the pineal gland at night. influences circadian and seasonal rhythms, most notably the sleep-wake cycle and seasonal reproduction. The neurochemical basis of these activities is not understood yet. Inhibition of dopamine release by melatonin has been demonstrated in specific areas of the mammalian central nervous system (hypothalamus, hippocampus, medulla-pons, and retina). Antidopaminergic activities of melatonin have been demonstrated in the striatum. Dopaminergic transmission has a pivotal role in circadian entrainment of the fetus, in coordination of body movement and reproduction. Recent findings indicate that melatonin may modulate dopaminergic pathways involved in movement disorders in humans. In Parkinson patients melatonin may, on the one hand, exacerbate symptoms (because of its putative interference with dopamine release) and, on the other, protect against neurodegeneration (by virtue of its antioxidant properties and its effects on mitochondrial activity). Melatonin appears to be effective in the treatment of tardive dyskinesia. a severe movement disorder associated with long-term blockade of the postsynaptic dopamine D2 receptor by antipsychotic drugs in schizophrenic patients. The interaction of melatonin with the dopaminergic system may play a significant role in the nonphotic and photic entrainment of the biological clock as well as in the fine-tuning of motor coordination in the striatum. These interactions and the antioxidant nature of melatonin may be beneficial in the treatment of dopamine-related disorders. PMID:12043836

  6. Diagnosis and treatment of pineal region tumors

    SciTech Connect

    Neuwelt, E.A.

    1984-01-01

    The aim of this volume is to review the pertinent literature dealing with pineal tumors and thus aid in the handling of these rather uncommon lesions. After the first, introductory, chapter, three chapters treat the pathology and diagnosis of pineal tumors. There is also one chapter on intracranial germ cell tumors (natural history and pathogenesis) and one on the normal function of the pineal gland. With the exception of the chapter on diagnostic radiology of pineal tumors, which seems somewhat superficial, these five chapters summarize current knowledge about the nature of these complex lesions and their symptomatology very well. The next nine chapters deal with biopsy and surgery of these tumors and how to manage the patient. The first of these gives a historical review of the development of surgical techniques - from the first attempt by Horsley in 1905 to the microsurgical techniques of today. It is followed by a very important and detailed description of the microsurgical anatomy of the pineal region.

  7. [The sexual peculiarities of aging changes in circannual rhythms of pineal gland, hypophysis, adrenal cortex and thymus functions in healthy subjects].

    PubMed

    Labunets, I F

    2013-01-01

    The interrelations of circannual rhythms of the functional state of pineal gland, hypophysis, adrenal cortex, thymus in healthy women and men from 20 to 79 years were studied. Fluctuations of melatonin, ACTH, cortisol and thymic serum factor, which were exchanged in aging (the season peaks of hormones and its acrophase) were found in blood of healthy 20-29 years old people. The changes of rhythmicity of indices were in male earlier (pineal gland and hypophysis over 30 years, thymus and adrenal cortex over 40 years) and more impressive than in women. The aging changes of pineal gland function's rhythm in healthy subjects have important role for changes of interrelations of circannual rhythms hypophysis, adrenal cortex and thymus.

  8. Experimental and clinical aspects of melatonin and clock genes in diabetes.

    PubMed

    Peschke, Elmar; Bähr, Ina; Mühlbauer, Eckhard

    2015-08-01

    The pineal hormone melatonin influences insulin secretion, as well as glucagon and somatostatin secretion, both in vivo and in vitro. These effects are mediated by two specific, high-affinity, seven transmembrane, pertussis toxin-sensitive, Gi-protein-coupled melatonin receptors, MT1 and MT2. Both isoforms are expressed in the β-cells, α-cells as well as δ-cells of the pancreatic islets of Langerhans and are involved in the modulation of insulin secretion, leading to inhibition of the adenylate cyclase-dependent cyclic adenosine monophosphate as well as cyclic guanosine monophosphate formation in pancreatic β-cells by inhibiting the soluble guanylate cyclase, probably via MT2 receptors. In this way, melatonin also likely inhibits insulin secretion, whereas using the inositol triphosphate pathway after previous blocking of Gi-proteins by pertussis toxin, melatonin increases insulin secretion. Desynchrony of receptor signaling may lead to the development of type 2 diabetes. This notion has recently been supported by genomewide association studies pinpointing variances of the MT2 receptor as a risk factor for this rapidly spreading metabolic disturbance. As melatonin is secreted in a clearly diurnal fashion, it is safe to assume that it also has a diurnal impact on the blood-glucose-regulating function of the islet. Observations of the circadian expression of clock genes (Clock, Bmal1, Per1,2,3, and Cry1,2) in pancreatic islets, as well as in INS1 rat insulinoma cells, may indicate that circadian rhythms are generated in the β-cells themselves. The circadian secretion of insulin from pancreatic islets is clock-driven. Disruption of circadian rhythms and clock function leads to metabolic disturbances, for example, type 2 diabetes. The study of melatonin-insulin interactions in diabetic rat models has revealed an inverse relationship between these two hormones. Both type 2 diabetic rats and patients exhibit decreased melatonin levels and slightly increased

  9. Effects of bucindolol on neurohormonal activation in congestive heart failure

    SciTech Connect

    Eichhorn, E.J.; McGhie, A.L.; Bedotto, J.B.; Corbett, J.R.; Malloy, C.R.; Hatfield, B.A.; Deitchman, D.; Willard, J.E.; Grayburn, P.A. )

    1991-01-01

    To examine the effects of beta-adrenergic blockade on neurohormonal activation in patients with congestive heart failure, 15 men had assessments of hemodynamics and supine peripheral renin and norepinephrine levels before and after 3 months of oral therapy with bucindolol, a nonselective beta antagonist. At baseline, plasma renin activity did not correlate with any hemodynamic parameter. However, norepinephrine levels had a weak correlation with left ventricular end-diastolic pressure (r = 0.74, p less than 0.01), stroke volume index (r = 0.61, p less than 0.02) and pulmonary vascular resistance (r = 0.54, p less than 0.05). Plasma renin decreased with bucindolol therapy, from 11.6 +/- 13.4 to 4.3 +/- 4.1 ng/ml/hour (mean +/- standard deviation; p less than 0.05), whereas plasma norepinephrine was unchanged, from 403 +/- 231 to 408 +/- 217 pg/ml. A wide diversity of the norepinephrine response to bucindolol was observed with reduction of levels in some patients and elevation in others. Although plasma norepinephrine did not decrease, heart rate tended to decrease (from 82 +/- 20 vs 73 +/- 11 min-1, p = 0.059) with beta-adrenergic blockade, suggesting neurohormonal antagonism at the receptor level. No changes in I-123 metaiodobenzylguanidine uptake occurred after bucindolol therapy, suggesting unchanged adrenergic uptake of norepinephrine with beta-blocker therapy. Despite reductions in plasma renin activity and the presence of beta blockade, the response of renin or norepinephrine levels to long-term bucindolol therapy did not predict which patients had improved in hemodynamic status (chi-square = 0.37 for renin, 0.82 for norepinephrine).

  10. Neuropeptide Y as a presynaptic modulator of norepinephrine release from the sympathetic nerve fibers in the pig pineal gland.

    PubMed

    Ziółkowska, N; Lewczuk, B; Przybylska-Gornowicz, B

    2015-01-01

    Norepinephrine (NE) released from the sympathetic nerve endings is the main neurotransmitter controlling melatonin synthesis in the mammalian pineal gland. Although neuropeptide Y (NPY) co-exists with NE in the pineal sympathetic nerve fibers it also occurs in a population of non-adrenergic nerve fibers located in this gland. The role of NPY in pineal physiology is still enigmatic. The present study characterizes the effect of NPY on the depolarization-evoked 3H-NE release from the pig pineal explants. The explants of the pig pineal gland were loaded with 3H-NE in the presence of pargyline and superfused with Tyrode medium. They were exposed twice to the modified Tyrode medium containing 60 mM of K+ to evoke the 3H-NE release via depolarization. NPY, specific agonists of Y1- and Y2- receptors and pharmacologically active ligands of α2-adrenoceptors were added to the medium before and during the second depolarization. The radioactivity was measured in medium fractions collected every 2 minutes during the superfusion. NPY (0.1-10 μM) significantly decreased the depolarization-induced 3H-NE release. Similar effect was observed after the treatment with Y2-agonist: NPY13-36, but not with Y1-agonist: [Leu31,Pro34]-NPY. The tritium overflow was lower in the explants exposed to the 5 μM NPY and 1 μM rauwolscine than to rauwolscine only. The effects of 5 μM NPY and 0.05 μM UK 14,304 on the depolarization-evoked 3H-NE release were additive. The results show that NPY is involved in the regulation of NE release from the sympathetic terminals in the pig pineal gland, inhibiting this process via Y2-receptors.

  11. Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats.

    PubMed

    Navarro-Alarcon, Miguel; Ruiz-Ojeda, Francisco J; Blanca-Herrera, Rosa M; Kaki, Abdullah; Adem, Abdu; Agil, Ahmad

    2014-03-01

    The use of melatonin, a neurohormone present in plants, represents an exciting approach for the maintenance of optimum health conditions. Melatonin administration ameliorates glucose homeostasis in Zucker diabetic fatty (ZDF) rats. The objective of this study was to investigate the effects of melatonin in diabetes in relation to the levels and regulation of plasma chromium (Cr), vanadium (V), and magnesium (Mg) in Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. At the age of 6 weeks, ZDF (n = 30) and ZL (n = 30) groups were each subdivided into three groups: control (C) (n = 10), vehicle-treated (V') (n = 10) and melatonin-treated (M) (10 mg kg(-1) per day; n = 10) groups for a 6 week period. After treatment, plasma mineral concentrations were measured by flame (Mg) and electrothermal (Cr and V) atomic absorption spectrometry. No significant differences were found between the C and V' groups (p > 0.05). Plasma Mg levels were significantly lower in C-ZDF vs. C-ZL rats, demonstrating the presence of hypomagnesemia in this diabetes mellitus model. Plasma V and Cr levels were significantly higher in M-ZDF vs. C-ZDF rats. Plasma Mg levels in ZDF rats were not affected by melatonin treatment (p > 0.05). Melatonin administration ameliorates the diabetic status of ZDF rats by enhancing plasma Cr and V concentrations. This appears to be the first report of a beneficial effect of melatonin treatment on plasma Cr and V regulation in ZDF rats.

  12. Pineal calcification and its relationship to the fatigue of multiple sclerosis.

    PubMed

    Sandyk, R; Awerbuch, G I

    1994-01-01

    Fatigue is one of the most common clinical features of multiple sclerosis (MS) and is a frequent cause of disability. The pathogenesis of fatigue remains obscure. It may result from impaired propagation of action potentials in areas of demyelination. Other contributors may be mental depression, immobility, and physical disability. The fatigue of MS may be relieved by diverse pharmacological drugs such as amantadine and pemoline, but the mechanisms by which these agents act to ameliorate fatigue are unknown. Attention has been focused recently on the relationship between MS and the pineal gland and evidence has been presented to implicate the pineal gland and melatonin in the pathogenesis of the disease. To investigate this relationship further, we studied in 47 MS patients (mean age: 41.6 +/- 9.9 yrs; mean duration of illness: 13.6 +/- 12.6 yrs) the association between fatigue and incidence of pineal calcification (PC) on CT scan, which is thought to reflect past secretory activity of the gland. For comparison, we also evaluated the incidence of choroid plexus calcification (CPC) in these patients. The sample included 20 patients who experienced ongoing, debilitating fatigue during the course of the disease. 27 patients who did not complain of fatigue served as controls. The two groups were not distinguishable with respect to age, sex, age of onset, chronicity, course (relapsing-remitting vs. chronic progressive), and severity of the disease (ambulatory vs. immobile), as well as the incidence of affective illness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7928120

  13. Melatonin has multiorgan effects.

    PubMed

    Opie, Lionel H; Lecour, Sandrine

    2016-10-01

    Melatonin, widely used to counter transatlantic travel jet lag and insomnia, is synthesized in the suprachiasmatic nucleus of the anterior pituitary gland. Its release into the circulation is stimulated by the onset of darkness, followed by a progressive decrease in blood levels with the onset of dawn. Melatonin administration can maintain the quality of sleep and help to counteract age-induced cognitive decline. Melatonin can also limit the severity of a variety of cardiovascular and cerebrovascular diseases, diabetes, and cancer. PMID:27533945

  14. Melatonin Inhibits CXCL10 and MMP-1 Production in IL-1β-Stimulated Human Periodontal Ligament Cells.

    PubMed

    Hosokawa, Ikuko; Hosokawa, Yoshitaka; Shindo, Satoru; Ozaki, Kazumi; Matsuo, Takashi

    2016-08-01

    Melatonin is a hormone that is mainly secreted by the pineal gland and exhibits a wide spectrum of activities, including antioxidant functions. Melatonin has been detected in gingival crevicular fluid. However, the role of melatonin in periodontal tissue is still uncertain. The aim of this study was to examine the effects of melatonin on inflammatory mediator expression in human periodontal ligament cells (HPDLC). Interleukin (IL)-1β induced CXC chemokine ligand (CXCL)10, matrix metalloproteinase (MMP)-1, and tissue inhibitors of metalloproteinase (TIMP)-1 production in HPDLC. Melatonin decreased CXCL10 and MMP-1 production and increased TIMP-1 production in IL-1β-stimulated HPDLC. Western blot analysis showed that melatonin inhibited p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK) phosphorylation, and IkB-α degradation and phosphorylation in IL-1β-stimulated HPDLC. These results suggest that melatonin might inhibit Th1 cell migration by reducing CXCL10 production. Moreover, melatonin might inhibit soft tissue destruction by decreasing MMP-1 production in periodontal lesions. PMID:27271323

  15. Melatonin Inhibits CXCL10 and MMP-1 Production in IL-1β-Stimulated Human Periodontal Ligament Cells.

    PubMed

    Hosokawa, Ikuko; Hosokawa, Yoshitaka; Shindo, Satoru; Ozaki, Kazumi; Matsuo, Takashi

    2016-08-01

    Melatonin is a hormone that is mainly secreted by the pineal gland and exhibits a wide spectrum of activities, including antioxidant functions. Melatonin has been detected in gingival crevicular fluid. However, the role of melatonin in periodontal tissue is still uncertain. The aim of this study was to examine the effects of melatonin on inflammatory mediator expression in human periodontal ligament cells (HPDLC). Interleukin (IL)-1β induced CXC chemokine ligand (CXCL)10, matrix metalloproteinase (MMP)-1, and tissue inhibitors of metalloproteinase (TIMP)-1 production in HPDLC. Melatonin decreased CXCL10 and MMP-1 production and increased TIMP-1 production in IL-1β-stimulated HPDLC. Western blot analysis showed that melatonin inhibited p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK) phosphorylation, and IkB-α degradation and phosphorylation in IL-1β-stimulated HPDLC. These results suggest that melatonin might inhibit Th1 cell migration by reducing CXCL10 production. Moreover, melatonin might inhibit soft tissue destruction by decreasing MMP-1 production in periodontal lesions.

  16. Melatonin in mood disorders.

    PubMed

    Srinivasan, Venkataramanujan; Smits, Marcel; Spence, Warren; Lowe, Alan D; Kayumov, Leonid; Pandi-Perumal, Seithikurippu R; Parry, Barbara; Cardinali, Daniel P

    2006-01-01

    The cyclic nature of depressive illness, the diurnal variations in its symptomatology and the existence of disturbed sleep-wake and core body temperature rhythms, all suggest that dysfunction of the circadian time keeping system may underlie the pathophysiology of depression. As a rhythm-regulating factor, the study of melatonin in various depressive illnesses has gained attention. Melatonin can be both a 'state marker' and a 'trait marker' of mood disorders. Measurement of melatonin either in saliva or plasma, or of its main metabolite 6-sulfatoxymelatonin in urine, have documented significant alterations in melatonin secretion in depressive patients during the acute phase of illness. Not only the levels but also the timing of melatonin secretion is altered in bipolar affective disorder and in patients with seasonal affective disorder (SAD). A phase delay of melatonin secretion takes place in SAD, as well as changes in the onset, duration and offset of melatonin secretion. Bright light treatment, that suppresses melatonin production, is effective in treating bipolar affective disorder and SAD, winter type. This review discusses the role of melatonin in the pathophysiology of bipolar disorder and SAD.

  17. Nature's knockout: the Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters.

    PubMed

    Weaver, D R; Liu, C; Reppert, S M

    1996-11-01

    The pineal hormone melatonin regulates seasonal reproduction and influences the timing of circadian rhythms. The Mel1a and Mel1b receptors are the high-affinity melatonin receptors present in mammals. Unexpectedly, the Mel1b receptor gene of the Siberian hamster, Phodopus sungorus, cannot encode a functional receptor; two nonsense mutations are present within the coding region. Southern blot analysis indicates that this is a single copy gene. The Mel1b receptor gene is nonfunctional in outbred populations of P. sungorus and Phodopus campbelli. Siberian hamsters lacking a functional Mel1b receptor nevertheless show seasonal reproductive and circadian responses to melatonin, indicating that the Mel1b receptor is not necessary for these responses. These data support the hypothesis that the Mel1a receptor, which does encode a functional receptor in this species, mediates reproductive and circadian responses to melatonin.

  18. Cartesian theories on the passions, the pineal gland and the pathogenesis of affective disorders: an early forerunner.

    PubMed

    López-Muñoz, F; Alamo, C

    2011-03-01

    The relationship between physical and functional alterations in the pineal gland, the 'passions' (emotions or feelings) and psychopathology has been a constant throughout the history of medicine. One of the most influential authors on this subject was René Descartes, who discussed it in his work The Treatise on the Passions of the Soul (1649). Descartes believed that 'passions' were sensitive movements that the soul, located in the pineal gland, experienced due to its union with the body, by circulating animal spirits. Descartes described sadness as one of the six primitive passions of the soul, which leads to melancholy if not remedied. Cartesian theories had a great deal of influence on the way that mental pathologies were considered throughout the entire 17th century and during much of the 18th century, but the link between the pineal gland and psychiatric disorders it was definitively highlighted in the 20th century, with the discovery of melatonin in 1958. The recent development of a new pharmacological agent acting through melatonergic receptors (agomelatine) has confirmed the close link between the pineal gland and affective disorders.

  19. Pgc-1α and Nr4a1 Are Target Genes of Circadian Melatonin and Dopamine Release in Murine Retina

    PubMed Central

    Kunst, Stefanie; Wolloscheck, Tanja; Kelleher, Debra K.; Wolfrum, Uwe; Sargsyan, S. Anna; Iuvone, P. Michael; Baba, Kenkichi; Tosini, Gianluca; Spessert, Rainer

    2015-01-01

    Purpose The neurohormones melatonin and dopamine mediate clock-dependent/circadian regulation of inner retinal neurons and photoreceptor cells and in this way promote their functional adaptation to time of day and their survival. To fulfill this function they act on melatonin receptor type 1 (MT1 receptors) and dopamine D4 receptors (D4 receptors), respectively. The aim of the present study was to screen transcriptional regulators important for retinal physiology and/or pathology (Dbp, Egr-1, Fos, Nr1d1, Nr2e3, Nr4a1, Pgc-1α, Rorβ) for circadian regulation and dependence on melatonin signaling/MT1 receptors or dopamine signaling/D4 receptors. Methods This was done by gene profiling using quantitative polymerase chain reaction in mice deficient in MT1 or D4 receptors. Results The data obtained determined Pgc-1α and Nr4a1 as transcriptional targets of circadian melatonin and dopamine signaling, respectively. Conclusions The results suggest that Pgc-1α and Nr4a1 represent candidate genes for linking circadian neurohormone release with functional adaptation and healthiness of retina and photoreceptor cells. PMID:26393668

  20. Atypical Teratomas of the Pineal

    PubMed Central

    Lewis, I.; Baxter, D. W.; Stratford, J. G.

    1963-01-01

    Atypical teratomas of the pineal were studied pathologically and clinically, and five illustrative cases are described. The results of three postmortem examinations are available, while two of the patients are living, one leading a normal life. Pathological verification revealed that two had suprasellar “ectopic” pinealomas. One neoplasm was located in the pineal (collicular) region. The histology of the tumours was identical, consisting of small cells resembling lymphocytes and large cells with prominent nucleoli and mitoses. This feature plus the midline location led to adoption of the term “atypical teratoma”. Patients with collicular pinealomas presented with headache, vomiting, papilledema, Parinaud's syndrome and, rarely, nystagmus retractorius. Diabetes insipidus, visual difficulty and hypopituitarism were characteristic features in those with suprasellar neoplasms. Treatment of collicular pinealoma has consisted of the use of a palliative shunt followed by a course of radiation. Chiasmal decompression and radiation have produced favourable results in patients with suprasellar pinealoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12 PMID:20327617

  1. Neuroprotective effect of melatonin in experimentally induced hypobaric hypoxia.

    PubMed

    Vornicescu, Corina; Boşca, Bianca; Crişan, Doiniţa; Yacoob, Sumaya; Stan, Nora; Filip, Adriana; Şovrea, Alina

    2013-01-01

    Melatonin (MEL) is an endogenous neurohormone with many biological functions, including a powerful antioxidant effect. The aim of the present study was to determine whether MEL protects the brain tissue from the oxidative stress induced by hypobaric hypoxia (HH) in vivo. This study was performed on Wistar rats randomly assigned in four groups, according to the pressure conditions and treatment: Group 1: normoxia and placebo; Group 2: HH and placebo; Group 3: normoxia and MEL; and Group 4: HH and MEL. The following aspects were evaluated: cognitive function (space reference and memory), oxidative stress parameters - serum and brain malondialdehyde (MDA) and reduced glutathione (GSH) levels -, and brain tissue macroscopic and microscopic morphological changes. Exposure to oxidative stress results in cognitive dysfunctions and biochemical alterations: significant increase of MDA and reduction of GSH in both serum and brain tissue. The most important morphological changes were observed in Group 2: increased cellularity, loss of pericellular haloes, shrunken neurons with scanty cytoplasm and hyperchromatic, pyknotic or absent nuclei; reactive gliosis, edema and blood-brain barrier alterations could also be observed in some areas. MEL treatment significantly diminished all these effects. Our results suggest that melatonin is a neuroprotective antioxidant both in normoxia and hypobaric hypoxia that can prevent and counteract the deleterious effects of oxidative stress (neuronal death, reactive astrogliosis, memory impairment and cognitive dysfunctions). Dietary supplements containing melatonin might be useful neuroprotective agents for the therapy of hypoxia-induced consequences. PMID:24399008

  2. Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease.

    PubMed

    Olcese, James M; Cao, Chuanhai; Mori, Takashi; Mamcarz, Malgorzata B; Maxwell, Anne; Runfeldt, Melissa J; Wang, Li; Zhang, Chi; Lin, Xiaoyang; Zhang, Guixin; Arendash, Gary W

    2009-08-01

    The neurohormone melatonin has been reported to exert anti-beta-amyloid aggregation, antioxidant, and anti-inflammatory actions in various in vitro and animal models. To comprehensively determine the potential for long-term melatonin treatment to protect Alzheimer's transgenic mice against cognitive impairment and development of beta-amyloid (Abeta) neuropathology, we administered melatonin (100 mg/L drinking water) to APP + PS1 double transgenic (Tg) mice from 2-2.5 months of age to their killing at age 7.5 months. A comprehensive behavioral battery administered during the final 6 weeks of treatment revealed that Tg mice given melatonin were protected from cognitive impairment in a variety of tasks of working memory, spatial reference learning/memory, and basic mnemonic function; Tg control mice remained impaired in all of these cognitive tasks/domains. Immunoreactive Abeta deposition was significantly reduced in hippocampus (43%) and entorhinal cortex (37%) of melatonin-treated Tg mice. Although soluble and oligomeric forms of Abeta1-40 and 1-42 were unchanged in the hippocampus and cortex of the same melatonin-treated Tg mice, their plasma Abeta levels were elevated. These Abeta results, together with our concurrent demonstration that melatonin suppresses Abeta aggregation in brain homogenates, are consistent with a melatonin-facilitated removal of Abeta from the brain. Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha were decreased in hippocampus (but not plasma) of Tg+ melatonin mice. Finally, the cortical mRNA expression of three antioxidant enzymes (SOD-1, glutathione peroxidase, and catalase) was significantly reduced to non-Tg levels by long-term melatonin treatment in Tg mice. Thus, melatonin's cognitive benefits could involve its anti-Abeta aggregation, anti-inflammatory, and/or antioxidant properties. Our findings provide support for long-term melatonin therapy as a primary or complementary strategy for abating the progression of

  3. Pineal Function: Impact of Microarray Analysis

    PubMed Central

    Klein, David C.; Bailey, Michael J.; Carter, David A.; Kim, Jong-so; Shi, Qiong; Ho, Anthony; Chik, Constance; Gaildrat, Pascaline; Morin, Fabrice; Ganguly, Surajit; Rath, Martin F.; Møller, Morten; Sugden, David; Rangel, Zoila G.; Munson, Peter J.; Weller, Joan L.; Coon, Steven L.

    2009-01-01

    Microarray analysis has provided a new understanding of pineal function by identifying genes that are highly expressed in this tissue relative to other tissues and also by identifying over 600 genes that are expressed on a 24-hour schedule. This effort has highlighted surprising similarity to the retina and has provided reason to explore new avenues of study including intracellular signaling, signal transduction, transcriptional cascades, thyroid/retinoic acid hormone signaling, metal biology, RNA splicing, and the role the pineal gland plays in the immune/inflammation response. The new foundation that microarray analysis has provided will broadly support future research on pineal function. PMID:19622385

  4. Bidirectional effect of electromagnetic fields on ketanserin-induced yawning in patients with multiple sclerosis: the role of melatonin.

    PubMed

    Sandyk, R

    1996-03-01

    5-HT2 receptors regulate sleep including yawning behavior. Ritanserin, a selective 5-HT2A receptor antagonist, increases the duration of slow wave in rats and humans. This effect is more pronounced during the light period when melatonin plasma levels are low; melatonin inhibits the sleep effects of ritanserin. These findings indicate that melatonin co-determines the effects of ritanserin on sleep. In a cohort of multiple sclerosis (MS) patients ketanserin, a selective 5-HT2A receptor antagonist, induces recurrent yawning particularly when administered in daytime. The frequency of yawning induced by the drug was modified by AC pulsed picotesla flux electromagnetic fields (EMFs) which affect melatonin secretion. Two MS patients are presented in whom the frequency of ketanserin-induced yawning was altered in opposite directions by these EMFs. The first patient, a 50 year old woman with a remitting-relapsing course, developed recurrent yawning and sleepiness after administration of ketanserin (10 mg, PO). Yawning was decreased dramatically during application of EMFs but was unaffected by a placebo EMFs treatment. The second patient, a 35 year old man with a chronic progressive course, manifested a single and brief yawn after administration of an equal dose of ketanserin. Yawning was increased dramatically during application of EMFs while remaining unchanged during a placebo EMFs treatment. These observations demonstrate a bidirectional effect of picotesla flux EMFs on ketanserin-induced yawning which may be related to differences in daytime melatonin plasma levels among MS patients. If validated by estimations of melatonin plasma levels in a larger cohort of patients the information derived from the effects of picotesla EMFs on ketanserin-induced yawning could be used to: (a) assess pineal melatonin functions in patients with MS; (b) indicate differences in pineal functions between male and female MS patients; and (c) indicate a relationship between plasma melatonin

  5. Daily differential expression of melatonin-related genes and clock genes in rat cumulus-oocyte complex: changes after pinealectomy.

    PubMed

    Coelho, L A; Peres, R; Amaral, F G; Reiter, R J; Cipolla-Neto, J

    2015-05-01

    This study investigated the maturational stage (immature and mature ovaries) differences of mRNA expression of melatonin-forming enzymes (Aanat and Asmt), melatonin membrane receptors (Mt1 and Mt2) and putative nuclear (Rorα) receptors, and clock genes (Clock, Bmal1, Per1, Per2, Cry1, Cry2) in cumulus-oocyte complexes (COC) from weaning Wistar rats. We also examined the effects of pinealectomy and of melatonin pharmacological replacement on the daily expression of these genes in COC. qRT-PCR analysis revealed that in oocytes, the mRNA expression of Asmt, Mt2, Clock, Bmal1, Per2, and Cry1 were higher (P < 0.05) in immature ovaries than in the mature ones. In cumulus cells, the same pattern of mRNA expression for Asmt, Aanat, Rorα, Clock, Per1, Cry1, and Cry2 genes was observed. In oocytes, pinealectomy altered the daily mRNA expression profiles of Asmt, Mt1, Mt2, Clock, Per1, Cry1, and Cry2 genes. In cumulus cells, removal of the pineal altered the mRNA expression profiles of Mt1, Mt2, Rorα, Aanat, Asmt, Clock, Bmal1, Per2, Cry1, and Cry2 genes. Melatonin treatment partially or completely re-established the daily mRNA expression profiles of most genes studied. The mRNA expression of melatonin-related genes and clock genes in rat COC varies with the maturational stage of the meiotic cellular cycle in addition to the hour of the day. This suggests that melatonin might act differentially in accordance with the maturational stage of cumulus/oocyte complex. In addition, it seems that circulating pineal melatonin is very important in the design of the daily profile of mRNA expression of COC clock genes and genes related to melatonin synthesis and action.

  6. Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair.

    PubMed

    Fischer, Tobias W; Slominski, Andrzej; Zmijewski, Michal A; Reiter, Russel J; Paus, Ralf

    2008-09-01

    Melatonin, one of the evolutionarily most ancient, highly conserved and most pleiotropic hormones still operative in man, couples complex tissue functions to defined changes in the environment. Showing photoperiod-associated changes in its activity levels in mammals, melatonin regulates, chronobiological and reproductive systems, coat phenotype and mammary gland functions. However, this chief secretory product of the pineal gland is now recognized to also exert numerous additional functions which range from free radical scavenging and DNA repair via immunomodulation, body weight control and the promotion of wound healing to the coupling of environmental cues to circadian clock gene expression and the modulation of secondary endocrine signalling (e.g. prolactin release, oestrogen receptor-mediated signalling). Some of these activities are mediated by high-affinity membrane (MT1, MT2) or specific cytosolic (MT3/NQO2) and nuclear hormone receptors (ROR alpha), while others reflect receptor-independent antioxidant activities of melatonin. Recently, it was shown that mammalian (including human) skin and hair follicles are not only melatonin targets, but also sites of extrapineal melatonin synthesis. Therefore, we provide here an update of the relevant cutaneous effects and mechanisms of melatonin, portray melatonin as a major skin protectant and sketch how its multi-facetted functions may impact on skin biology and pathology. This is illustrated by focussing on recent findings on the role of melatonin in photodermatology and hair follicle biology. After listing a number of key open questions, we conclude by defining particularly important, clinically relevant perspectives for how melatonin may become therapeutically exploitable in cutaneous medicine. PMID:18643846

  7. Marked reduction of radiation-induced micronuclei in human blood lymphocytes pretreated with melatonin

    SciTech Connect

    Vijayalaxmi; Reiter, R.J.; Leal, B.Z.

    1995-07-01

    Human peripheral blood lymphocytes which were pretreated in vitro with melatonin, and endogenously synthesized pineal hormone, for 20 min at 37 {plus_minus} 1{degrees}C exhibited a significant and concentration-dependent reduction in the frequency of {gamma}radiation-induced micronuclei compared with irradiated cells which did not receive the pretreatment. The extent of the reduction observed with 2.0 mM melatonin was similar to that found in lymphocytes pretreated for 20 min with 1.0 M dimethylsulfoxide, a known free radical scavenger. These observations indicate that melatonin may have an active role in protection of humans against genetic damage due to endogenously produced free radicals, and also may be of use in reducing damage due to exposure to physical and chemical mutagens and carcinogens which generate free radicals. 25 refs., 2 tabs.

  8. Calcium-signaling components in rat insulinoma β-cells (INS-1) and pancreatic islets are differentially influenced by melatonin.

    PubMed

    Bazwinsky-Wutschke, Ivonne; Mühlbauer, Eckhard; Albrecht, Elke; Peschke, Elmar

    2014-05-01

    The pineal secretory product melatonin exerts its influence on the insulin secretion of pancreatic islets by different signaling pathways. The purpose of this study was to analyze the impact of melatonin on calcium-signaling components under different conditions. In a transfected INS-1 cell line overexpressing the human MT2 receptor (hMT2-INS-1), melatonin treatment induced even stronger depressive effects on calcium/calmodulin-dependent kinase 2d and IV (Camk2d, CamkIV) transcripts during 3-isobutyl-1-methylxanthine (IBMX) treatment than in normal INS-1 cells, indicating a crucial influence of melatonin receptor density on transcript-level regulation. In addition, melatonin induced a significant downregulation of calmodulin (Calm1) in IBMX-treated hMT2-INS-1 cells. Long-term administration of melatonin alone reduced CamkIV transcript levels in INS-1 cells; however, transcript levels of Camk2d remained unchanged. The release of insulin was diminished under long-term melatonin treatment. The impact of melatonin also involved reductions in CAMK2D protein during IBMX or forskolin treatments in INS-1 cells, as measured by an enzyme-linked immunosorbent assay, indicating a functional significance of transcriptional changes in pancreatic islets. Furthermore, analysis of melatonin receptor knockout mice showed that the transcript levels of Camk2d, CamkIV, and Calm1 were differentially influenced according to the melatonin receptor subtype deleted. In conclusion, this study provides evidence that melatonin has different impacts on the regulation of Calm1 and Camk. These calcium-signaling components are known as participants in the calcium/calmodulin pathway, which plays an important functional role in the modulation of the β-cell signaling pathways leading to insulin secretion.

  9. Melatonin ameliorates dexamethasone-induced inhibitory effects on the proliferation of cultured progenitor cells obtained from adult rat hippocampus.

    PubMed

    Ekthuwapranee, Kasima; Sotthibundhu, Areechun; Tocharus, Chainarong; Govitrapong, Piyarat

    2015-01-01

    Glucocorticoids, hormones that are released in response to stress, induce neuronal cell damage. The hippocampus is a primary target of glucocorticoids in the brain, the effects of which include the suppression of cell proliferation and diminished neurogenesis in the dentate gyrus. Our previous study found that melatonin, synthesized primarily in the pineal, pretreatment prevented the negative effects of dexamethasone, the glucocorticoid receptor agonist, on behavior and neurogenesis in rat hippocampus. In the present study, we attempted to investigate the interrelationship between melatonin and dexamethasone on the underlying mechanism of neural stem cell proliferation. Addition of dexamethasone to hippocampal progenitor cells from eight-week old rats resulted in a decrease in the number of neurospheres; pretreatment with melatonin precluded these effects. The immunocytochemical analyses indicated a reduction of Ki67 and nestin-positive cells in the dexamethasone-treated group, which was minimized by melatonin pretreatment. A reduction of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation and G1-S phase cell cycle regulators cyclin E and CDK2 in dexamethasone-treated progenitor cells were prevented by pretreatment of melatonin. Moreover, luzindole, a melatonin receptor antagonist blocked the positive effect of melatonin whereas RU48, the glucocorticoid receptor antagonist blocked the negative effect of dexamethasone on the number of neurospheres. Moreover, we also found that dexamethasone increased the glucocorticoid receptor protein but decreased the level of MT1 melatonin receptor, whereas melatonin increased the level of MT1 melatonin receptor but decreased the glucocorticoid receptor protein. These suggest the crosstalk and cross regulation between the melatonin receptor and the glucocorticoid receptor on hippocampal progenitor cell proliferation.

  10. Evidence of melatonin secretion in cetaceans: plasma concentration and extrapineal HIOMT-like presence in the bottlenose dolphin Tursiops truncatus.

    PubMed

    Panin, Mattìa; Gabai, Gianfranco; Ballarin, Cristina; Peruffo, Antonella; Cozzi, Bruno

    2012-06-01

    The pineal gland is generally believed to be absent in cetaceans, although few and subsequently unconfirmed reports described the organ in some species. The recent description of a complete and photographed pineal body in a bottlenose dolphin (Tursiops truncatus) prompted us to examine a series of 29 brains of the same species, but no gland was found. We then decided to investigate if the main product of the gland, melatonin, was nevertheless produced and present in the plasma of this species. We collected plasma and serum samples from a series of captive bottlenose dolphins for a period of 7 months spanning from winter to summer and we determined the indoleamine concentration by radio-immunoassay (RIA). The results demonstrated for the first time a quantitative assessment of melatonin production in the blood of a cetacean. Melatonin levels were comparable to those of terrestrial mammals (5.15-27.74 pg/ml daylight concentration), with indications of both seasonal and daily variation although the presence of a circadian rhythm remains uncertain. Immunohistochemical analyses using as a marker hydroxyindole-O-methyl-transferase (HIOMT, the key enzyme involved in the biosynthesis of the hormone), suggested extrapineal melatonin production by the retina, the Harderian gland and the gut. The enzyme was unequivocally localized in all the three tissues, and, specifically, ganglion cells in the retina showed a very strong HIOMT-immunoreactivity. Our results suggest that further research might reveal unexplored aspects of melatonin production in cetaceans and deserves special attention and further efforts. PMID:22554922

  11. Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on the Rat Pineal Transcriptome

    PubMed Central

    Hartley, Stephen W.; Coon, Steven L.; Savastano, Luis E.; Mullikin, James C.; Fu, Cong; Klein, David C.

    2015-01-01

    The term neurotranscriptomics is used here to describe genome-wide analysis of neural control of transcriptomes. In this report, next-generation RNA sequencing was using to analyze the effects of neonatal (5-days-of-age) surgical stimulus deprivation on the adult rat pineal transcriptome. In intact animals, more than 3000 coding genes were found to exhibit differential expression (adjusted-p < 0.001) on a night/day basis in the pineal gland (70% of these increased at night, 376 genes changed more than 4-fold in either direction). Of these, more than two thousand genes were not previously known to be differentially expressed on a night/day basis. The night/day changes in expression were almost completely eliminated by neonatal removal (SCGX) or decentralization (DCN) of the superior cervical ganglia (SCG), which innervate the pineal gland. Other than the loss of rhythmic variation, surgical stimulus deprivation had little impact on the abundance of most genes; of particular interest, expression levels of the melatonin-synthesis-related genes Tph1, Gch1, and Asmt displayed little change (less than 35%) following DCN or SCGX. However, strong and consistent changes were observed in the expression of a small number of genes including the gene encoding Serpina1, a secreted protease inhibitor that might influence extracellular architecture. Many of the genes that exhibited night/day differential expression in intact animals also exhibited similar changes following in vitro treatment with norepinephrine, a superior cervical ganglia transmitter, or with an analog of cyclic AMP, a norepinephrine second messenger in this tissue. These findings are of significance in that they establish that the pineal-defining transcriptome is established prior to the neonatal period. Further, this work expands our knowledge of the biological process under neural control in this tissue and underlines the value of RNA sequencing in revealing how neurotransmission influences cell biology. PMID

  12. Calcification of the pineal gland: relationship to laterality of the epileptic foci in patients with complex partial seizures.

    PubMed

    Sandyk, R

    1992-01-01

    The right and left temporal lobes differ from each other with respect to the rate of intrauterine growth, the timing of maturation, rate of aging, anatomical organization, neurochemistry, metabolic rate, electroencephalographic measures, and function. These functional differences between the temporal lobes underlies the different patterns of psychopathology and endocrine reproductive disturbances noted in patients with temporolimbic epilepsy. The right hemisphere has greater limbic and reticular connections than the left. Since the pineal gland receives direct innervation from the limbic system and the secretion of melatonin is influenced by an input from the reticular system, I propose that lesions in the right temporal lobe have a greater impact on pineal melatonin functions as opposed to those in the left dominant temporal lobe. Consequently, since calcification of the pineal gland is thought to reflect past secretory activity of the gland, I predicted a higher prevalence of pineal calcification (PC) in epileptic patients with right temporal lobe as opposed to those with left temporal lobe foci. To investigate this hypothesis, the prevalence of PC on CT scan was studied in a sample of 70 patients (43 men, 27 women, mean age: 29.2 years, range 9-58; SD = 10.1) with complex partial seizures, of whom 49 (70.0%) had a right temporal lobe focus. PC was present in 51 patients (72.8%) and was unrelated to any of the historical and demographic data surveyed. In the patients with a focus in the right temporal lobe, PC was present in 46 cases (93.8%) as compared to 5 of 21 patients (23.8%) with left temporal lobe foci.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1341678

  13. Melatonin decreases cell proliferation, impairs myogenic differentiation and triggers apoptotic cell death in rhabdomyosarcoma cell lines.

    PubMed

    Codenotti, Silvia; Battistelli, Michela; Burattini, Sabrina; Salucci, Sara; Falcieri, Elisabetta; Rezzani, Rita; Faggi, Fiorella; Colombi, Marina; Monti, Eugenio; Fanzani, Alessandro

    2015-07-01

    Melatonin is a small indole produced by the pineal gland and other tissues, and has numerous functions that aid in the maintenance of the whole body homeostasis, ranging from the regulation of circadian rhythms and sleep to protection from oxidative stress. Melatonin has also been reported to counteract cell growth and chemoresistance in different types of cancer. In the present study, we investigated the effects of exogenous melatonin administration on different human cell lines and primary mouse tumor cultures of rhabdomyosarcoma (RMS), the most frequent soft tissue sarcoma affecting childhood. The results showed that melatonin significantly affected the behavior of RMS cells, leading to inhibition of cell proliferation and impairment of myogenic differentiation followed by increased apoptotic cell death, as observed by immunoblotting analysis of apoptosis-related markers including Bax, Bcl-2 and caspase-3. Similar findings were observed using a combination of microscopy techniques, including scanning/transmission electron and confocal microscopy. Furthermore, melatonin in combination with doxorubicin or cisplatin, two compounds commonly used for the treatment of solid tumors, increased the sensitivity of RMS cells to apoptosis. These data indicated that melatonin may be effective in counteracting RMS tumor growth and chemoresistance.

  14. Role of melatonin on production and preservation of gametes and embryos: a brief review.

    PubMed

    Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde; da Cruz, Jurandir Ferreira; Tan, Dun-Xian; Reiter, Russel J

    2014-03-01

    The aim of this brief review is to clarify the role of melatonin in the production and preservation of mammalian gametes and embryos. Melatonin is an indoleamine synthesized from tryptophan in the pineal gland and other organs that operates as a hypothalamic-pituitary-gonadal axis modulator and regulates the waxing and waning of seasonal reproductive competence in photoperiodic mammals. A major function of the melatonin rhythm is to transmit information about the length of the daily photoperiod to the circadian and circannual systems in order to provide time-of-day and time-of-year information, respectively, to the organism. Melatonin is also a powerful antioxidant and anti-apoptotic agent, which is due to its direct scavenging of toxic oxygen derivatives and its ability to reduce the formation of reactive species. Mammalian gametes and embryos are highly vulnerable to oxidative stress due to the presence of high lipid levels; during artificial breeding procedures, these structures are exposed to dramatic changes in the microenvironment, which have a direct bearing on their function and viability. Free radicals influence the balance between oxidation-reduction reactions, disturb the transbilayer-phospholipid asymmetry of the plasma membrane and enhance lipid peroxidation. Melatonin, due to its amphiphilic nature, is undoubtedly useful in tissues by protecting them from free radical-mediated oxidative damage and cellular death. The supplementation of melatonin to semen extender or culture medium significantly improves sperm viability, oocyte competence and blastocyst development in vitro. PMID:24559971

  15. Melatonin's role in preventing toxin-related and sepsis-mediated hepatic damage: A review.

    PubMed

    Esteban-Zubero, Eduardo; Alatorre-Jiménez, Moisés Alejandro; López-Pingarrón, Laura; Reyes-Gonzales, Marcos César; Almeida-Souza, Priscilla; Cantín-Golet, Amparo; Ruiz-Ruiz, Francisco José; Tan, Dun-Xian; García, José Joaquín; Reiter, Russel J

    2016-03-01

    The liver is a central organ in detoxifying molecules and would otherwise cause molecular damage throughout the organism. Numerous toxic agents including aflatoxin, heavy metals, nicotine, carbon tetrachloride, thioacetamide, and toxins derived during septic processes, generate reactive oxygen species followed by molecular damage to lipids, proteins and DNA, which culminates in hepatic cell death. As a result, the identification of protective agents capable of ameliorating the damage at the cellular level is an urgent need. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other organs and many studies confirm its benefits against oxidative stress including lipid peroxidation, protein mutilation and molecular degeneration in various organs, including the liver. Recent studies confirm the benefits of melatonin in reducing the cellular damage generated as a result of the metabolism of toxic agents. These protective effects are apparent when melatonin is given as a sole therapy or in conjunction with other potentially protective agents. This review summarizes the published reports that document melatonin's ability to protect hepatocytes from molecular damage due to a wide variety of substances (aflatoxin, heavy metals, nicotine, carbon tetrachloride, chemotherapeutics, and endotoxins involved in the septic process), and explains the potential mechanisms by which melatonin provides these benefits. Melatonin is an endogenously-produced molecule which has a very high safety profile that should find utility as a protective molecule against a host of agents that are known to cause molecular mutilation at the level of the liver. PMID:26808084

  16. Inter-relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity.

    PubMed

    Szewczyk-Golec, Karolina; Woźniak, Alina; Reiter, Russel J

    2015-10-01

    Obesity and its medical complications represent a significant problem throughout the world. In recent decades, mechanisms underlying the progression of obesity have been intensively examined. The involvement of both the behavioral aspects, such as calorie-rich diet, low physical activity and sleep deprivation, and the intrinsic factors, including adipose tissue deregulation, chronic inflammation, oxidative stress, and chronodisruption, has been identified. The circadian disturbances of the adipose tissue endocrine function have been correlated with obesity. Leptin and adiponectin are adipokines strongly associated with glucose and lipid metabolism and with energy balance. Their synthesis and secretion display circadian rhythms that are disturbed in the obese state. Hyperleptinemia resulting in leptin resistance, and hypo-adiponectinemia have been linked to the pathophysiology of the obesity-related disorders. A deficiency of melatonin, one of the consequences of sleep deprivation, has also been demonstrated to correlate with obesity. Melatonin is a pineal secretory product involved in numerous actions, such as regulation of internal biological clocks and energy metabolism, and it functions as an antioxidant and as an anti-inflammatory agent. There exists a substantial amount of evidence supporting the beneficial effects of melatonin supplementation on obesity and its complications. In the current review, the results of studies related to the interactions between melatonin, and both leptin and adiponectin are discussed. Despite the existence of some inconsistencies, melatonin has been found to normalize the expression and secretion patterns of both adipokines. These results support the concept of melatonin as a potential therapeutic agent for obesity and related disorders.

  17. Role of melatonin on production and preservation of gametes and embryos: a brief review.

    PubMed

    Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde; da Cruz, Jurandir Ferreira; Tan, Dun-Xian; Reiter, Russel J

    2014-03-01

    The aim of this brief review is to clarify the role of melatonin in the production and preservation of mammalian gametes and embryos. Melatonin is an indoleamine synthesized from tryptophan in the pineal gland and other organs that operates as a hypothalamic-pituitary-gonadal axis modulator and regulates the waxing and waning of seasonal reproductive competence in photoperiodic mammals. A major function of the melatonin rhythm is to transmit information about the length of the daily photoperiod to the circadian and circannual systems in order to provide time-of-day and time-of-year information, respectively, to the organism. Melatonin is also a powerful antioxidant and anti-apoptotic agent, which is due to its direct scavenging of toxic oxygen derivatives and its ability to reduce the formation of reactive species. Mammalian gametes and embryos are highly vulnerable to oxidative stress due to the presence of high lipid levels; during artificial breeding procedures, these structures are exposed to dramatic changes in the microenvironment, which have a direct bearing on their function and viability. Free radicals influence the balance between oxidation-reduction reactions, disturb the transbilayer-phospholipid asymmetry of the plasma membrane and enhance lipid peroxidation. Melatonin, due to its amphiphilic nature, is undoubtedly useful in tissues by protecting them from free radical-mediated oxidative damage and cellular death. The supplementation of melatonin to semen extender or culture medium significantly improves sperm viability, oocyte competence and blastocyst development in vitro.

  18. Melatonin induces gene-specific effects on rhythmic mRNA expression in the pars tuberalis of the Siberian hamster (Phodopus sungorus).

    PubMed

    Wagner, Gabriela C; Johnston, Jonathan D; Tournier, Benjamin B; Ebling, Francis J P; Hazlerigg, David G

    2007-01-01

    In mammals, circadian and photoperiodic information is encoded in the pineal melatonin signal. The pars tuberalis (PT) of the pituitary is a melatonin target tissue, which transduces photoperiodic changes and drives seasonal changes in prolactin secretion from distal lactotroph cells. Measurement of photoperiodic time in the PT is believed to occur through melatonin dependent changes in clock gene expression, although it is unclear whether the PT should be considered a melatonin sensitive peripheral oscillator. We tested this hypothesis in the Siberian hamster (Phodopus sungorus) firstly by investigating the effects of melatonin injection, and secondly by determining whether temporal variation in gene expression within the PT persists in the absence of a rhythmic melatonin signal. Hamsters preconditioned to long days were treated with melatonin during the late light phase, to advance the timing of the nocturnal melatonin peak, or placed in constant light for one 24 h cycle, thereby suppressing endogenous melatonin secretion. Gene expression in the PT was measured by in situ hybridization. We show that melatonin rapidly induces cry1 mRNA expression without the need for a prolonged melatonin-free interval, acutely inhibits mt1 expression, advances the timing of peak rev-erb alpha expression and modulates per1 expression. With the exception of cry1, these genes continue to show temporal changes in expression over a first cycle in the absence of a melatonin signal. Our data are consistent with the hypothesis that the hamster PT contains a damped endogenous circadian oscillator, which requires a rhythmic melatonin signal for long-term synchronization.

  19. Dissociation of circadian and light inhibition of melatonin release through forced desynchronization in the rat.

    PubMed

    Schwartz, Michael D; Wotus, Cheryl; Liu, Tiecheng; Friesen, W Otto; Borjigin, Jimo; Oda, Gisele A; de la Iglesia, Horacio O

    2009-10-13

    Pineal melatonin release exhibits a circadian rhythm with a tight nocturnal pattern. Melatonin synthesis is regulated by the master circadian clock within the hypothalamic suprachiasmatic nucleus (SCN) and is also directly inhibited by light. The SCN is necessary for both circadian regulation and light inhibition of melatonin synthesis and thus it has been difficult to isolate these two regulatory limbs to define the output pathways by which the SCN conveys circadian and light phase information to the pineal. A 22-h light-dark (LD) cycle forced desynchrony protocol leads to the stable dissociation of rhythmic clock gene expression within the ventrolateral SCN (vlSCN) and the dorsomedial SCN (dmSCN). In the present study, we have used this protocol to assess the pattern of melatonin release under forced desynchronization of these SCN subregions. In light of our reported patterns of clock gene expression in the forced desynchronized rat, we propose that the vlSCN oscillator entrains to the 22-h LD cycle whereas the dmSCN shows relative coordination to the light-entrained vlSCN, and that this dual-oscillator configuration accounts for the pattern of melatonin release. We present a simple mathematical model in which the relative coordination of a single oscillator within the dmSCN to a single light-entrained oscillator within the vlSCN faithfully portrays the circadian phase, duration and amplitude of melatonin release under forced desynchronization. Our results underscore the importance of the SCN's subregional organization to both photic input processing and rhythmic output control.

  20. Diurnal and circadian regulation of a melatonin receptor, MT1, in the golden rabbitfish, Siganus guttatus.

    PubMed

    Park, Yong-Ju; Park, Ji-Gweon; Hiyakawa, Nanae; Lee, Young-Don; Kim, Se-Jae; Takemura, Akihiro

    2007-01-15

    The golden rabbitfish Siganus guttatus is a reef fish with a restricted lunar-synchronized spawning rhythmicity and releases gametes simultaneously around the first quarter moon period during the spawning season. In order to understand the molecular aspects of the "circa" rhythms in this species, the full-length melatonin receptor (MT1) cDNA was cloned, and its diurnal/circadian regulation was examined. The full-length MT1 cDNA (1257 bp) contained an open reading frame that encodes a protein of 350 amino acids; this protein is highly homologous to MT1 of nonmammalian species. A high expression of MT1 mRNA with a day-night difference was observed in the whole brain, retina, liver, and kidney. When diurnal variations in MT1 mRNA expression in the retina and whole brain were examined using real-time quantitative RT-PCR, an increase in the mRNA expression was observed during nighttime in both tissues under conditions of light/dark, constant darkness, and constant light. This suggests that MT1 mRNA expression is under circadian regulation. The expression of MT1 mRNA in the cultured pineal gland also showed diurnal variations with high expression levels during nighttime; this suggests that the increased expression level observed in the whole brain is partially of pineal origin. Alternation of light conditions in the pineal gland cultures resulted in the changes in melatonin release into the culture medium as well as MT1 mRNA expression in the pineal gland. The present results suggest that melatonin and its receptors play an important role in the exertion of daily and circadian variations in the neural tissues.

  1. Computed tomographic evaluation of pineal calcification.

    PubMed

    Kohli, N; Rastogi, H; Bhadury, S; Tandon, V K

    1992-04-01

    A prospective study to ascertain the incidence of normally calcified pineal gland, was carried out in 1000 consecutive patients from different parts of Uttar Pradesh (India), undergoing cranial computed tomography for reasons other than a pineal or parapineal pathology. A total of 167 (16.70%) patients were found to have calcified pineals. Of these 128 were males and 39 females. The incidence rose from 1.16 per cent in the first decade to 31.88 per cent above the age of 50 yr. The percentage incidence of normal pineal calcification was lower than that seen in the Western population. No significant difference was found between men and women in any age group. Although calcification appeared as early as the first decade, this percentage was significantly lower than in the higher age groups. Significantly higher incidence rates were seen in the second decade, third decade and sixth decade onwards. PMID:1428055

  2. [Characteristics of the pineal gland and thymus relationship in aging].

    PubMed

    Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M; Trofimov, A V; Sevost'ianova, N N

    2011-01-01

    The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

  3. Pineal anlage tumor in a 5-month-old boy.

    PubMed

    Olaya, Joffre E; Raghavan, Ravi; Totaro, Laura; Zouros, Alexander

    2010-06-01

    Pineal tumors are rare neoplasms that are categorized into pineoblastomas, pineocytomas, and pineal parenchymal tumors of intermediate differentiation. Pineal anlage tumors are primary pineal tumors with neuroepithelial and ectomesenchymal differentiation and without endodermal differentiation. The authors review the literature and report the case of a 5-month-old boy with a pineal anlage tumor. This is only the sixth case of a pineal anlage tumor reported in the English-language literature adding to the understanding of this tumor's presentation, immunomorphological and molecular characteristics, embryological origin, radiological appearance, treatment outcome, and prognosis.

  4. Cavernous angioma of the pineal region.

    PubMed

    Donati, P; Maiuri, F; Gangemi, M; Gallicchio, B; Sigona, L

    1992-01-01

    The pineal region is one of the most rare localizations of intracranial cavernous angiomas, with only 8 cases reported up today. The Authors report a case of cavernous angioma of such localization and review the pertinent literature. Magnetic resonance allows the correct diagnosis of cavernous malformations on the basis of their typical aspect, even in the absence of histological verification. We suggest that this imaging technique will allow to identify more frequently pineal cavernomas preoperatively, thus avoiding useless irradiation. PMID:1484302

  5. History of the pineal region tumor.

    PubMed

    Mottolese, C; Szathmari, A

    2015-01-01

    The pineal gland has interested humans from millenniums. In this paper we review back in the history and the evolution of the pineal gland surgery. Originally, this surgery used to carry a high rate of morbidity and mortality. Nowadays the development of the anesthetic, radiological, surgical and intensive care techniques have been responsible of an improvement of the surgical results and better quality of life. It is always interesting to know from where we come.

  6. Circadian changes in long noncoding RNAs in the pineal gland

    PubMed Central

    Coon, Steven L.; Munson, Peter J.; Cherukuri, Praveen F.; Sugden, David; Rath, Martin F.; Møller, Morten; Clokie, Samuel J. H.; Fu, Cong; Olanich, Mary E.; Rangel, Zoila; Werner, Thomas; Mullikin, James C.; Klein, David C.; Benjamin, Betty; Blakesley, Robert; Bouffard, Gerry; Brooks, Shelise; Chu, Grace; Coleman, Holly; Dekhtyar, Mila; Gregory, Michael; Guan, Xiaobin; Gupta, Jyoti; Han, Joel; Hargrove, April; Ho, Shi-ling; Johnson, Taccara; Legaspi, Richelle; Lovett, Sean; Maduro, Quino; Masiello, Cathy; Maskeri, Baishali; McDowell, Jenny; Montemayor, Casandra; Novotny, Betsy; Park, Morgan; Riebow, Nancy; Schandler, Karen; Schmidt, Brian; Sison, Christina; Stantripop, Mal; Thomas, James; Vemulapalli, Meg; Young, Alice

    2012-01-01

    Long noncoding RNAs (lncRNAs) play a broad range of biological roles, including regulation of expression of genes and chromosomes. Here, we present evidence that lncRNAs are involved in vertebrate circadian biology. Differential night/day expression of 112 lncRNAs (0.3 to >50 kb) occurs in the rat pineal gland, which is the source of melatonin, the hormone of the night. Approximately one-half of these changes reflect nocturnal increases. Studies of eight lncRNAs with 2- to >100-fold daily rhythms indicate that, in most cases, the change results from neural stimulation from the central circadian oscillator in the suprachiasmatic nucleus (doubling time = 0.5–1.3 h). Light exposure at night rapidly reverses (halving time = 9–32 min) levels of some of these lncRNAs. Organ culture studies indicate that expression of these lncRNAs is regulated by norepinephrine acting through cAMP. These findings point to a dynamic role of lncRNAs in the circadian system. PMID:22864914

  7. Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome

    PubMed Central

    Potocki, L.; Glaze, D.; Tan, D.; Park, S.; Kashork, C.; Shaffer, L.; Reiter, R.; Lupski, J.

    2000-01-01

    BACKGROUND—Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome associated with a hemizygous deletion of chromosome 17, band p11.2. Characteristic features include neurobehavioural abnormalities such as aggressive and self-injurious behaviour and significant sleep disturbances. The majority of patients have a common deletion characterised at the molecular level. Physical mapping studies indicate that all patients with the common deletion are haploinsufficient for subunit 3 of the COP9 signalosome (COPS3), which is conserved from plants to humans, and in the plant Arabidopis thaliana regulates gene transcription in response to light. Haploinsufficiency of this gene is hypothesised to be potentially involved in the sleep disturbances seen in these patients. Melatonin is a hormone secreted by the pineal gland. SMS patients are reported to have fewer sleep disturbances when given a night time dose of this sleep inducing hormone.
METHODS—Urinary excretion of 6-sulphatoxymelatonin (aMT6s), the major hepatic metabolite of melatonin, in 19 SMS patients were measured in conjunction with 24 hour sleep studies in 28 SMS patients. Five of the 28 patients did not have the common SMS deletion. To investigate a potential correlation of COPS3 haploinsufficiency and disturbed melatonin excretion, we performed fluorescence in situ hybridisation (FISH) using two BACs containing coding exons of COPS3.
RESULTS—All SMS patients show significant sleep disturbances when assessed by objective criteria. Abnormalities in the circadian rhythm of aMT6s were observed in all but one SMS patient. Interestingly this patient did not have the common deletion. All patients studied, including the one patient with a normal melatonin rhythm, were haploinsufficient for COPS3.
CONCLUSIONS—Our data indicate a disturbed circadian rhythm in melatonin and document the disturbed sleep pattern in Smith-Magenis syndrome. Our findings suggest that the

  8. Inhibition of cell proliferation: a mechanism likely to mediate the prevention of neuronal cell death by melatonin.

    PubMed

    Mayo, J C; Sainz, R M; Uría, H; Antolín, I; Estéban, M M; Rodríguez

    1998-08-01

    In a previous work we demonstrated that melatonin is able to prevent apoptosis induced by low doses of 6-hydroxydopamine (6-OHDA) in undifferentiated and neuronal PC12 cells. We also reported how this neurohormone was able to prevent the decrease in the mRNA for antioxidant enzymes caused by 6-OHDA. Although the antioxidant capability of melatonin seems to be clearly implicated in its antiapoptotic activity, literature suggests that its antiproliferative property could also be involved in its prevention of apoptosis. In the present work we demonstrated that melatonin is able to inhibit cell proliferation in undifferentiated PC12 cells, decreasing cell number and the total amount of DNA, and the mRNA for the histone H4, which are known to increase during DNA synthesis. Melatonin does not decrease the number of cells in nonproliferating PC12 cells, indicating that it does not cause cell death. Additionally, we demonstrate that other inhibitors of cell proliferation, as well as other antioxidants, are able to mimic the antiapoptotic effect of melatonin. This is interpreted to mean that melatonin acts by both mechanisms to inhibit apoptosis caused by 6-OHDA and the findings support the hypothesis of a relationship between oxidative stress and regulation of the cell cycle.

  9. Role of Exogenous Melatonin on Cell Proliferation and Oxidant/Antioxidant System in Aluminum-Induced Renal Toxicity.

    PubMed

    Karabulut-Bulan, Omur; Bayrak, Bertan Boran; Arda-Pirincci, Pelin; Sarikaya-Unal, Guner; Us, Huseyin; Yanardag, Refiye

    2015-11-01

    Aluminum has toxic potential on humans and animals when it accumulates in various tissues. It was shown in a number of studies that aluminum causes oxidative stress by free radical formation and lipid peroxidation in tissues and thus may cause damage in target organs. Although there are numerous studies investigating aluminum toxicity, biochemical mechanisms of the damage caused by aluminum have yet to be explained. Melatonin produced by pineal gland was shown to be an effective antioxidant. Since kidneys are target organs for aluminum accumulation and toxicity, we have studied the role of melatonin against aluminum-induced renal toxicity in rats. Wistar albino rats were divided into five groups. Group I served as control, and received only physiological saline; group II served as positive control for melatonin, and received ethanol and physiological saline; group III received melatonin (10 mg/kg); group IV received aluminum sulfate (5 mg/kg) and group V received aluminum sulfate and melatonin (in the same dose), injected three times a week for 1 month. Administration of aluminum caused degenerative changes in renal tissues, such as increase in metallothionein immunoreactivity and decrease in cell proliferation. Moreover, uric acid and lipid peroxidation levels and xanthine oxidase activity increased, while glutathione, catalase, superoxide dismutase, paraoxonase 1, glucose-6-phosphate dehydrogenase, and sodium potassium ATPase activities decreased. Administration of melatonin mostly prevented these symptoms. Results showed that melatonin is a potential beneficial agent for reducing damage in aluminum-induced renal toxicity.

  10. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

    PubMed Central

    Delagrange, Philippe; Krause, Diana N.; Sugden, David; Cardinali, Daniel P.; Olcese, James

    2010-01-01

    The hormone melatonin (5-methoxy-N-acetyltryptamine) is synthesized primarily in the pineal gland and retina, and in several peripheral tissues and organs. In the circulation, the concentration of melatonin follows a circadian rhythm, with high levels at night providing timing cues to target tissues endowed with melatonin receptors. Melatonin receptors receive and translate melatonin's message to influence daily and seasonal rhythms of physiology and behavior. The melatonin message is translated through activation of two G protein-coupled receptors, MT1 and MT2, that are potential therapeutic targets in disorders ranging from insomnia and circadian sleep disorders to depression, cardiovascular diseases, and cancer. This review summarizes the steps taken since melatonin's discovery by Aaron Lerner in 1958 to functionally characterize, clone, and localize receptors in mammalian tissues. The pharmacological and molecular properties of the receptors are described as well as current efforts to discover and develop ligands for treatment of a number of illnesses, including sleep disorders, depression, and cancer. PMID:20605968

  11. Urinary Excretion of Melatonin and Association with Breast Cancer: Meta-Analysis and Review of the Literature

    PubMed Central

    Basler, Michelle; Jetter, Alexander; Fink, Daniel; Seifert, Burkhardt; Kullak-Ublick, Gerd A.; Trojan, Andreas

    2014-01-01

    Summary Background Melatonin is an endocrine hormone secreted by the pineal gland during night hours that provides several biological functions in the circadian rhythm of humans. Due to anti-estrogenic properties, melatonin is considered to exhibit a protective role against the development of breast cancer (BC). Moreover, disruption of melatonin production through environmental influences, such as night work, is assumed to be a risk factor for BC. Materials and Methods We reviewed recent findings concerning biological effects of melatonin on BC and conducted a meta-analysis to evaluate the association between melatonin and BC incidence. In random and fixed effects statistical models, concentrations (tertiles, quartiles) of the primary urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), were tested for the assumption that women with the highest values would exhibit a lower risk of BC. Results Statistical analysis of data from 5 prospective case-control studies indicates an inverse association between BC risk and the highest levels of urinary aMT6s. This effect seems to be influenced by lag intervals between aMT6s collection and the occurrence of BC, timing and methods of urine sampling, as well as genetic and environmental factors. Conclusion On the basis of the results of our meta-analysis, melatonin is likely to affect BC occurrence in women. However, methodological dissonances may require further studies. PMID:25177260

  12. Melatonin and Oral Cavity

    PubMed Central

    Cengiz, Murat İnanç; Cengiz, Seda; Wang, Hom-Lay

    2012-01-01

    While initially the oral cavity was considered to be mainly a source of various bacteria, their toxins and antigens, recent studies showed that it may also be a location of oxidative stress and periodontal inflammation. Accordingly, this paper focuses on the involvement of melatonin in oxidative stress diseases of oral cavity as well as on potential therapeutic implications of melatonin in dental disorders. Melatonin has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue, and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a coadjuvant in the treatment of certain conditions of the oral cavity. However, the most important effect of melatonin seems to result from its potent antioxidant, immunomodulatory, protective, and anticancer properties. Thus, melatonin could be used therapeutically for instance, locally, in the oral cavity damage of mechanical, bacterial, fungal, or viral origin, in postsurgical wounds caused by tooth extractions and other oral surgeries. Additionally, it can help bone formation in various autoimmunological disorders such as Sjorgen syndrome, in periodontal diseases, in toxic effects of dental materials, in dental implants, and in oral cancers. PMID:22792106

  13. Seasonal postembryonic maturation of the diurnal rhythm of serotonin in the chicken pineal gland.

    PubMed

    Piesiewicz, Aneta; Kedzierska, Urszula; Turkowska, Elzbieta; Adamska, Iwona; Majewski, Pawel M

    2015-02-01

    Previously, we have demonstrated the postembryonic development of chicken (Gallus gallus domesticus L.) pineal gland functions expressed as changes in melatonin (MEL) biosynthesis. Pineal concentrations of MEL and its precursor serotonin (5-HT) were shown to increase between the 2nd and 16th day of life. We also found that levels of the mRNAs encoding the enzymes participating in the final two steps of MEL biosynthesis from 5-HT: arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), as well as their enzymatic activities, were raised during postembryonic development. Moreover, the manner of these changes was season-of-hatch dependent, even in animals kept under constant laboratory conditions (L:D 12:12). The most pronounced changes were seen in the concentrations of 5-HT and MEL, as well as in Aanat mRNA level and its enzymatic activity. The high daily variability in 5-HT content suggested that season- and age-dependent changes in the activity of the chicken pineal gland might rely on the availability of 5-HT, i.e. it may be limited by changes in pineal tryptophan (TRP) and/or 5-hydroxytryptophan (5-HTP) levels as well as by the activity of tryptophan hydroxylase (TPH) and aromatic l-amino acid decarboxylase (AADC): two enzymes participating in the conversion of TRP to 5-HT. The present study was undertaken with the following objectives: (1) to examine whether the pineal concentration of the 5-HT precursors TRP and 5-HTP exhibit age- and season-related changes; (2) to look for season-related differences in the transcription of the Tph1 and Ddc genes encoding enzymes TPH and AADC; (3) to identify the step(s) in postembryonic development in which these season-related variations in pineal gland function are most pronounced. Male Hy-line chickens hatched in the summer or winter, from eggs laid by hens held in L:D 16:8 conditions were kept from the day of hatch in L:D 12:12 conditions. At the age of 2 or 9 days, animals were sacrificed

  14. Protective effect of melatonin against zonisamide-induced reproductive disorders in male rats

    PubMed Central

    Abdu, Faiza

    2013-01-01

    Introduction Zonisamide (ZNS) is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. The pineal hormone melatonin is involved in the regulation of reproductive function, including the timing of the luteinizing hormone (LH) surge. The aim of the present work was to study the protective effect of melatonin against the potential suppression impact of ZNS on reproductive activity. Material and methods Ninety adult albino male rats were allocated to several groups treated with melatonin (10 mg/kg BW), ZNS (10, 20 and 50 mg/kg BW) and 10 mg/kg of melatonin plus ZNS (10, 20 or 50 mg/kg BW, respectively). Reproductive hormones (testosterone, LH and follicle-stimulating hormone (FSH)) levels were measured in animal serum. Sperm abnormalities and DNA fragmentation in testis tissues as well as expression alteration of several reproductive-related genes were analyzed. Results The results revealed that ZNS decreased the levels of serum free testosterone, LH, and FSH and expression of their encoding genes in male rats. In addition, ZNS treatment increased the sperm abnormalities and DNA fragmentation and inducible nitric oxide synthase (iNOS) in testis tissues as well as GABA level in liver tissues. However, melatonin supplementation inhibited the negative symptoms of ZNS in which it increased the levels of reproductive hormones and expression of their encoding genes in the ZNS-treated rats. Moreover, melatonin decreased the sperm abnormalities, DNA fragmentation, iNOS activity and GABA level in ZNS-treated rats. Conclusions The data obtained in this study suggest that melatonin administration confers protection against toxicity inflicted by ZNS, and support the contention that melatonin protection is achieved by its ability as a scavenger for free radicals generated by ZNS. PMID:26170862

  15. Evidence for a direct effect of melatonin on mitochondrial genome expression of Siberian hamster brown adipocytes.

    PubMed

    Prunet-Marcassus, B; Ambid, L; Viguerie-Bascands, N; Pénicaud, L; Casteilla, L

    2001-03-01

    Photoperiod variations are known to participate in the regulation of energy balance in different rodent species via melatonin, a neurosecretory product synthesized by the pineal gland during the night. A direct effect of melatonin on adipose tissue has been suggested since binding sites for the indole have been described on brown adipocytes. The aim of this study was to investigate a genetic effect of melatonin on isolated Siberian hamster brown adipocytes using differential display RT-PCR (DDRT-PCR). Brown adipose cells were isolated from brown adipose tissue and treated for 3 hr with 0.1 and 10 microM melatonin. Total RNA was extracted and DDRT-PCR experiments were performed. A differential band, which disappeared after melatonin treatment, was detected. After confirmation and cloning, the corresponding cDNA fragment B18 was sequenced. B18 had 85 and 81% similarity with a portion of rat and mouse cytochrome b mRNA, respectively, suggesting that B18 corresponds to hamster cytochrome b. This hypothesis was confirmed by the close parallel between the changes in mRNA content, detected by B18, and by cytochrome b mRNA content, detected by a rat probe. Cytochrome b mRNA is encoded by the mitochondrial genome, suggesting a similar effect of melatonin on the whole mitochondrial transcripts. Indeed, 3 hr of treatment with melatonin (10 nM and 0.1 microM) decreased by 44% mitochondrial transcript contents. This work constitutes the first evidence of a direct biological effect of melatonin on Siberian hamster brown adipocytes.

  16. Plasma melatonin and urinary 6-hydroxymelatonin levels in patients with pulmonary tuberculosis.

    PubMed

    Ozkan, Esin; Yaman, Halil; Cakir, Erdinc; Deniz, Omer; Oztosun, Muzaffer; Gumus, Seyfettin; Akgul, Emin Ozgur; Agilli, Mehmet; Cayci, Tuncer; Kurt, Yasemin Gulcan; Aydin, Ibrahim; Arslan, Yakup; Ilhan, Nevin; Ilhan, Necip; Erbil, Mehmet Kemal

    2012-08-01

    Tuberculosis (TB) is the second most frequent cause of death in the world, after AIDS. Delay in diagnosing TB is an important worldwide problem. It seriously threatens public health. Cell-mediated immune responses play an important role in the pathogenesis of TB infection. The course of Mycobacterium tuberculosis (MTb) infection is regulated by two distinct T cell cytokine patterns. Melatonin is a biomolecule (mainly secreted by the pineal gland) with free radical scavenging, antioxidant and immunoregulatory properties. Melatonin has both its direct and indirect immunomodulatory effects on the immune system. In this study, we measured plasma melatonin and urine 6-hydroxy melatonin sulphate (6-HMS) concentrations in patients with newly diagnosed TB for the purpose of investigating whether there was a relationship between their levels and MTb infection. Thirty-one newly diagnosed patients presenting with active TB and 31 healthy subjects as the control group were included in this study. Blood and 24-h urine samples were collected from all individuals. Plasma melatonin levels and urine 6-HMS were measured. Our results show that in patients with TB, mean melatonin and 6-HMS concentrations were significantly lower than in the control subjects (p = 0.037, p < 0.001, respectively). We believe that the treatment of TB patients with melatonin might result in a wide range of health benefits including improved quality of life and reduced severity of infection in these patients. Supplementation with melatonin may be considered as an adjunctive therapy to classic treatment of pulmonary TB, especially during the acute phase of infection.

  17. Melatonin, a potent agent in antioxidative defense: Actions as a natural food constituent, gastrointestinal factor, drug and prodrug

    PubMed Central

    Hardeland, Rüdiger; Pandi-Perumal, SR

    2005-01-01

    Melatonin, originally discovered as a hormone of the pineal gland, is also produced in other organs and represents, additionally, a normal food constituent found in yeast and plant material, which can influence the level in the circulation. Compared to the pineal, the gastrointestinal tract contains several hundred times more melatonin, which can be released into the blood in response to food intake and stimuli by nutrients, especially tryptophan. Apart from its use as a commercial food additive, supraphysiological doses have been applied in medical trials and pure preparations are well tolerated by patients. Owing to its amphiphilicity, melatonin can enter any body fluid, cell or cell compartment. Its properties as an antioxidant agent are based on several, highly diverse effects. Apart from direct radical scavenging, it plays a role in upregulation of antioxidant and downregulation of prooxidant enzymes, and damage by free radicals can be reduced by its antiexcitatory actions, and presumably by contributions to appropriate internal circadian phasing, and by its improvement of mitochondrial metabolism, in terms of avoiding electron leakage and enhancing complex I and complex IV activities. Melatonin was shown to potentiate effects of other antioxidants, such as ascorbate and Trolox. Under physiological conditions, direct radical scavenging may only contribute to a minor extent to overall radical detoxification, although melatonin can eliminate several of them in scavenger cascades and potentiates the efficacy of antioxidant vitamins. Melatonin oxidation seems rather important for the production of other biologically active metabolites such as N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), which have been shown to also dispose of protective properties. Thus, melatonin may be regarded as a prodrug, too. AMK interacts with reactive oxygen and nitrogen species, conveys protection to mitochondria, inhibits and downregulates

  18. Melatonin and Other Tryptophan Metabolites Produced by Yeasts: Implications in Cardiovascular and Neurodegenerative Diseases

    PubMed Central

    Hornedo-Ortega, Ruth; Cerezo, Ana B.; Troncoso, Ana M.; Garcia-Parrilla, M. Carmen; Mas, Albert

    2016-01-01

    Yeast metabolism produces compounds derived from tryptophan, which are found in fermented beverages, such as wine and beer. In particular, melatonin and serotonin, may be relevant due to their bioactivity in humans. Indeed, the former is a neurohormone related to circadian rhythms, which also has a putative protective effect against degenerative diseases. Moreover, serotonin is a neurotransmitter itself, in addition to being a precursor of melatonin synthesis. This paper summarizes data reported on fermented beverages, to evaluate dietary intake. Additionally, the article reviews observed effects of yeast amino acid metabolites on the prevention of neurodegenerative diseases (Alzheimer’s and Parkinson’s) and angiogenesis, focusing on evidence of the molecular mechanism involved and identification of molecular targets. PMID:26834716

  19. Inhibition of isoproterenol-induced lipolysis in rat inguinal adipocytes in vitro by physiological melatonin via a receptor-mediated mechanism.

    PubMed

    Zalatan, F; Krause, J A; Blask, D E

    2001-09-01

    Because the pineal hormone melatonin has been implicated in affecting adiposity in rats and fatty acid transport in certain rat tumor models, we tested whether melatonin regulates lipolysis in a normal cell system in vitro. Adipocytes were isolated from the inguinal fat pads (i.e. sc fat) of Sprague Dawley male rats during mid-light phase. Lipolysis was stimulated with isoproterenol (3 microM), and cells were incubated for 4 h in the presence or absence of a physiological circulating concentration of melatonin (1 nM). Lipolysis was measured by determining the amount of glycerol present in the incubation buffer, expressed as nmol glycerol/mg cellular fatty acid. We observed a 20- to 30-fold stimulation of basal lipolysis by isoproterenol, and this stimulation was inhibited 50--70% by melatonin. Melatonin exhibited this effect over a wide range of concentrations tested (100 pM-1 microM) with an IC(50) of approximately 500 pM. The effect by melatonin (1 nM) was completely blocked by pertussis toxin (50 ng/ml), by 8-bromo-cAMP (10 nM), and by the melatonin receptor antagonist S-20928 (1 nM). These results suggest that the antilipolytic effect occurs through one of the G(i) protein-coupled melatonin receptors because we have shown that both the mt(1) (Mel 1a) and MT(2) (Mel 1b) melatonin receptors are expressed in inguinal adipocytes. Melatonin inhibition of lipolysis was not observed in adipocytes isolated from rat epididymal fat pads (i.e. visceral fat), even though these cells also express both the mt(1) and MT(2) receptors. The results indicate that physiological circulating concentrations of melatonin inhibit isoproterenol-induced lipolysis in rat adipocytes via a G protein-coupled melatonin receptor-mediated signal transduction pathway in a site-specific manner.

  20. Diffusion characteristics of pediatric pineal tumors

    PubMed Central

    Whitehead, Matthew T; Siddiqui, Adeel; Klimo, Paul; Boop, Frederick A

    2015-01-01

    Background Diffusion weighted imaging (DWI) has been shown to be helpful in characterizing tumor cellularity, and predicting histology. Several works have evaluated this technique for pineal tumors; however studies to date have not focused on pediatric pineal tumors. Objective We evaluated the diffusion characteristics of pediatric pineal tumors to confirm if patterns seen in studies using mixed pediatric and adult populations remain valid. Materials and methods This retrospective study was performed after Institutional Review Board approval. We retrospectively evaluated all patients 18 years of age and younger with pineal tumors from a single institution where preoperative diffusion weighted imaging as well as histologic characterization was available. Results Twenty patients (13 male, 7 female) with pineal tumors were identified: seven with pineoblastoma, four with Primitive Neuroectodermal Tumor (PNET), two with other pineal tumors, and seven with germ cell tumors including two germinomas, three teratomas, and one mixed germinoma-teratoma. The mean apparent diffusion coefficient (ADC) values in pineoblastoma (544 ± 65 × 10–6 mm2/s) and pineoblastoma/PNET (595 ± 144 × 10–6 mm2/s) was lower than that of the germ cell tumors (1284 ± 334 × 10–6 mm2/s; p < 0.0001 vs pineoblastoma). One highly cellular germinoma had an ADC value of 694 × 10–6 mm2/s. Conclusion ADC values can aid in differentiation of pineoblastoma/PNET from germ cell tumors in a population of children with pineal masses. PMID:25963154

  1. Pineal cyst: a review of clinical and radiological features.

    PubMed

    Choy, Winward; Kim, Won; Spasic, Marko; Voth, Brittany; Yew, Andrew; Yang, Isaac

    2011-07-01

    Pineal cysts (PCs) are benign and often asymptomatic lesions of the pineal region that are typically small and do not change in size over time. PCs appear as small, well circumscribed, unilocular masses that either reside within or completely replace the pineal gland. This article reviews and discusses the characteristic features of PCs-clinical, histological, and identifiable by various imaging modalities-which assist clinicians in narrowing the differential diagnosis for pineal lesions. PMID:21801982

  2. Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

    PubMed Central

    Lin, Gu-Jiun; Huang, Shing-Hwa; Chen, Shyi-Jou; Wang, Chih-Hung; Chang, Deh-Ming; Sytwu, Huey-Kang

    2013-01-01

    Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease. PMID:23727938

  3. Melatonin role preventing steatohepatitis and improving liver transplantation results.

    PubMed

    Esteban-Zubero, Eduardo; García-Gil, Francisco Agustín; López-Pingarrón, Laura; Alatorre-Jiménez, Moisés Alejandro; Ramírez, José Manuel; Tan, Dun-Xian; García, José Joaquín; Reiter, Russel J

    2016-08-01

    Liver steatosis is a prevalent process that is induced due to alcoholic or non-alcoholic intake. During the course of these diseases, the generation of reactive oxygen species, followed by molecular damage to lipids, protein and DMA occurs generating organ cell death. Transplantation is the last-resort treatment for the end stage of both acute and chronic hepatic diseases, but its success depends on ability to control ischemia-reperfusion injury, preservation fluids used, and graft quality. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other because of its efficacy in organs; melatonin has been investigated to improve the outcome of organ transplantation by reducing ischemia-reperfusion injury and due to its synergic effect with organ preservation fluids. Moreover, this indolamine also prevent liver steatosis. That is important because this disease may evolve leading to an organ transplantation. This review summarizes the observations related to melatonin beneficial actions in organ transplantation and ischemic-reperfusion models. PMID:27022943

  4. Melatonin and sleep in humans.

    PubMed

    Dawson, D; Encel, N

    1993-08-01

    Early studies on the physiological effects of melatonin typically reported hypnotic 'side-effects'. Later studies, specifically addressing this action, failed to reliably replicate hypnotic effects using standard polysomnography. This difference may be related to differences in the basic physiological action of melatonin compared with more conventional hypnotics. It is suggested that melatonin exerts a hypnotic effect through thermoregulatory mechanisms. By lowering core body temperature, melatonin reduces arousal and increases sleep-propensity. Thus, in humans, one role of melatonin is to transduce the light-dark cycle and define a window-of-opportunity in which sleep-propensity is enhanced. As such, melatonin is likely to be an effective hypnotic agent for sleep disruption associated with elevated temperature due to low circulating melatonin levels. The combined circadian and hypnotic effects of melatonin suggest a synergistic action in the treatment of sleep disorders related to the inappropriate timing of sleep and wakefulness. Adjuvant melatonin may also improve sleep disruption caused by drugs known to alter normal melatonin production (e.g., beta-blockers and benzodiazepines). If melatonin is to be developed as a successful clinical treatment, differences between the pharmacological profile following exogenous administration and the normal endogenous rhythm should be minimized. Continued development as a useful clinical tool requires control of both the amplitude and duration of the exogenous melatonin pulse. There is a need to develop novel drug delivery systems that can reliably produce a square-wave pulse of melatonin at physiological levels for 8-10 hr duration.

  5. HDAC1 inhibition by melatonin leads to suppression of lung adenocarcinoma cells via induction of oxidative stress and activation of apoptotic pathways.

    PubMed

    Fan, Chongxi; Pan, Yunhu; Yang, Yang; Di, Shouyin; Jiang, Shuai; Ma, Zhiqiang; Li, Tian; Zhang, Zhipei; Li, Weimiao; Li, Xiaofei; Reiter, Russel J; Yan, Xiaolong

    2015-10-01

    Melatonin is an indoleamine synthesized in the pineal gland that shows a wide range of physiological and pharmacological functions, including anticancer effects. In this study, we investigated the effect of melatonin on drug-induced cellular apoptosis against the cultured human lung adenocarcinoma cells and explored the role of histone deacetylase (HDAC) signaling in this process. The results showed that melatonin treatment led to a dose- and time-dependent decrease in the viability of human A549 and PC9 lung adenocarcinoma cells. Additionally, melatonin exhibited potent anticancer activity in vitro, as evidenced by reductions of the cell adhesion, migration, and the intracellular glutathione (GSH) level and increases in the apoptotic index, caspase 3 activity, and reactive oxygen species (ROS) in A549 and PC9 cells. Melatonin treatment also influenced the expression of HDAC-related molecules (HDAC1 and Ac-histone H3), upregulated the apoptosis-related molecules (PUMA and Bax), and downregulated the proliferation-related molecule (PCNA) and the anti-apoptosis-related molecule (Bcl2). Furthermore, the inhibition of HDAC signaling using HDAC1 siRNA or SAHA (a potent pan-inhibitor of HDACs) sensitized A549 and PC9 cells to the melatonin treatment. In summary, these data indicate that in vitro-administered melatonin is a potential suppressor of lung adenocarcinoma cells by the targeting of HDAC signaling and suggest that melatonin in combination with HDAC inhibitors may be a novel therapeutic intervention for human lung adenocarcinoma.

  6. The midline pineal "eye": MR and CT characteristics of the pineal gland with and without benign cyst formation.

    PubMed

    Jinkins, J R; Xiong, L; Reiter, R J

    1995-09-01

    The purpose of this study was to evaluate the magnetic resonance imaging characteristics of pineal cysts and pineal calcifications and to determine the incidence of benign pineal cysts. Two-hundred-fifty magnetic resonance examinations were retrospectively examined for the incidence of pineal cysts. In addition, 60 collected cases of pineal cysts were evaluated with regard to cross sectional diameter and magnetic resonance signal characteristics. Finally, the magnetic resonance signal characteristics of pineal tissue in 50 patients were compared to companion computed tomographic scans that were scrutinized for the presence or absence of calcification. The incidence of pineal cysts as revealed by magnetic resonance imaging in this study was 10.8%. The minimal and maximal measurements ranged from a low of 2 x 2 x 2 mm to a high of 10 x 12 x 10 mm. The magnetic resonance signal intensities of pineal cyst as compared to cerebrospinal fluid were iso- or hyperintense on all magnetic resonance sequences in the majority of cases. Calcifications of the pineal gland as revealed by computed tomography tended to be isointense to gray matter if the calcifications were small and hypointense to gray matter if large on all magnetic resonance acquisitions. A careful analysis of the magnetic resonance signal characteristics enables the recognition of moderate- to large-sized pineal calcifications and their differentiation from large pineal cysts. However, small cysts of the pineal gland can be difficult or impossible to distinguish on magnetic resonance imaging from calcifications without comparison with computed tomography. PMID:8609598

  7. Role of photoperiod and melatonin in seasonal acclimatization of the djungarian hamster, Phodopus sungorus

    NASA Astrophysics Data System (ADS)

    Steinlechner, S.; Heldmaier, G.

    1982-12-01

    The Djungarian hamster, Phodopus sungorus, shows a clear annual cycle in some thermogenic parameters such as nonshivering thermogenesis (NST) and cold resistance. These seasonal changes were found to be basically controlled by natural changes in photoperiod. Further support for this view was obtained by exposing the hamsters to artificial long and short photoperiods. Implantation of melatonin during fall and winter results in an increased thermogenic capacity in both short and long day hamsters comparable to that shown by values of control hamsters exposed to short photoperiods during winter. This thermotropic action of melatonin and of short photoperiod could be found only in fall and winter whereas during spring and summer, melatonin, like photoperiod, had no influence on thermogenic capacities. These results show that the actions of melatonin and photoperiod vary with the season and that they depend upon the photoperiodic history of the hamsters. Our results further indicate that the pineal gland with its hormone melatonin is involved in mediation of photoperiodic control of seasonal acclimatization.

  8. Melatonin treatment prevents modulation of cell-mediated immune response induced by propoxur in rats.

    PubMed

    Suke, Sanvidhan G; Pathak, Rahul; Ahmed, Rafat S; Tripathi, A K; Banerjee, B D

    2008-08-01

    The effect of melatonin, a major secretory product of the pineal gland, in attenuation of propoxur (2-isopropoxy phenyl N-methyl carbamate)-induced modulation of cell-mediated immune (CMI) response was studied in rats. Male Wistar albino rats were exposed to propoxur (a widely used pesticide) orally (10 mg/kg) and/or melatonin (10 mg/kg) orally for 4 weeks. CMI was measured by delayed-type hypersensitivity (DTH), leucocyte and macrophage migration inhibition (LMI and MMI) responses and estimation of cytokines TNF-alpha and IFN-gamma levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-alpha and IFN-gamma production significantly. Administration of melatonin alone caused a significant increase in DTH response. Although there were no changes in the LMI and MMI response, the cytokine levels were significantly increased, as compared to control. Co-administration of melatonin along with propoxur significantly nullified the effect of the pesticide on the CMI response, except DTH and reversed levels of cytokines to near control/normal values. Thus, melatonin treatment considerably attenuated immunomodulation caused by sub-chronic treatment of propoxur in experimental animals.

  9. Cytoprotective Effects of Melatonin Against Amitriptyline-Induced Toxicity in Isolated Rat Hepatocytes

    PubMed Central

    Taziki, Shohreh; Sattari, Mohammad Reza; Dastmalchi, Siavoush; Eghbal, Mohammad Ali

    2015-01-01

    Purpose: Amitriptyline, one of the commonly used tricyclic antidepressants, caused rare but severe hepatotoxicity in patients who received it continuously. Previous findings showed that the intermediate metabolites of amitriptyline produced by CYP450 are involved in hepatic injury. Melatonin is an antiaging and antioxidant hormone synthesized from pineal gland. The aim of present study was to evaluate the protective role of melatonin in an in vitro model of isolated rat hepatocytes. Methods: Markers such as cell viability, reactive oxygen species formation, lipid peroxidation, mitochondrial membrane potential, and hepatocytes glutathione content were evaluated every 60 minutes for 180 minutes. Results: Present results indicated that administration of 1mM of melatonin effectively reduced the cell death, ROS formation and lipid peroxidation, mitochondrial membrane potential collapse, and reduced cellular glutathione content caused by amitriptyline. Conclusion: Our results indicated that melatonin is an effective antioxidant in preventing amitriptyline-induced hepatotoxicity. We recommend further in vivo animal and clinical trial studies on the hepatoprotective effects of melatonin in patients receiving amitriptyline. PMID:26504754

  10. Retention and metabolic fate of [3H]-melatonin in the spotted skunk.

    PubMed

    Berria, M; Mead, R A

    1990-01-01

    Two experiments were designed to determine which tissues accumulate [3H]-melatonin and the metabolic fate of this hormone in the spotted skunk. Tritiated melatonin was injected into the jugular vein of 10 anesthetized skunks 1-3 h before the onset of darkness and allowed to circulate for 22 min before the vasculature was flushed with saline to clear radioactivity from the blood. Selected tissues were removed from five skunks and oxidized in a Packard Biological Oxidizer which yielded 95 +/- 5% recovery of radioactivity. Relatively high amounts of radioactivity were found in the pineal (367 +/- 304 dpm/mg tissue), ovary (69 +/- 38 dpm/mg), pituitary (89 +/- 56 dpm/mg), liver (107 +/- 29 dpm/mg), and kidney (63 +/- 15 dpm/mg). Relatively small amounts of [3H] were found in different brain regions (approximately 6-7 dpm/mg). The uterus, pancreas, and temporalis muscle also accumulated radioactivity (approximately 13 dpm/mg). The lung retained the least amount of radioactivity (4 +/- 1.3 dpm/mg). In the second experiment, hypothalami, pituitaries, and ovaries were removed from the remaining five females. Radioactivity from these tissues was extracted and subjected to thin-layer chromatography. Melatonin accounted for approximately 70% of the radioactivity recovered while 6-hydroxymelatonin and unidentified more polar compounds made up the majority of the melatonin metabolites. These data indicate that tissues other than the hypothalamus are able to accumulate [3H]-melatonin.

  11. Pineal parenchymal tumor of intermediate differentiation.

    PubMed

    Patil, Meena; Karandikar, Manjiri

    2015-01-01

    The 2007 World Health Organization classification of tumors of the central nervous system identified "pineal parenchymal tumor of intermediate differentiation" (PPTID) as a new pineal parenchymal neoplasm, located between pineocytoma and pineoblastoma as grade II or III. Because of the small number of reported cases, the classification of PPT is still a matter of controversy. We report a case of PPTID. A 25-year-old female patient was admitted to hospital with complaints of a headache, nausea, vomiting since 1-year. Computed tomography/magnetic resonance imaging of the brain showed well-defined, mildly enhancing lesion in the region of the pineal gland with areas of calcification. The tumor was excised. After 3 years, she presented with metastasis in thoracic and lumbosacral spinal region. This is a rare event. PMID:26549088

  12. CT and MR of pineal region tumors.

    PubMed

    Gouliamos, A D; Kalovidouris, A E; Kotoulas, G K; Athanasopoulou, A K; Kouvaris, J R; Trakadas, S J; Vlahos, L J; Papavasiliou, C G

    1994-01-01

    Magnetic Resonance (MR) imaging features of pineal region tumors were analyzed in 14 oncologic cases. The tumors were classified as germ-cell tumors, glial tumors, pineal parenchymal tumors, meningiomas, and cysts. They demonstrated different MR signal characteristics on precontrast scans and nodular or ring type enhancement with occasional central lucencies, except for benign cysts, which have not shown enhancement. MR images were useful in defining the relationship of the tumor to the posterior third ventricle, sylvian aqueduct, vein of Galen, and tentorium. Although CT can demonstrate in more evident fashion displacement of the original pineal calcification as well as tumor calcifications, MR imaging demonstrates different signal characteristics in germinomas and pineoblastomas which can be a useful adjunct in the evaluation and differential diagnosis of these tumors. PMID:8295504

  13. Pineal anlage tumour - a rare entity with divergent histology.

    PubMed

    Ahuja, Arvind; Sharma, Mehar Chand; Suri, Vaishali; Sarkar, Chitra; Sharma, B S; Garg, Ajay

    2011-06-01

    Pineal anlage tumour is a rare tumour of the pineal gland that is not listed in the 2007 World Health Organization classification of tumours of the central nervous system. Pineal anlage has been defined as a primary pineal tumour with both neuroepithelial and ectomesenchymal differentiation but without endodermal differentiation. We report a pineal anlage tumour in a 4-month-old boy, the youngest patient reported with this rare tumour, with a brief review of the literature. Clinicians and neuropathologists should be aware of this entity as it is likely to be misdiagnosed as a teratoma or a melanocytic tumour of the central nervous system.

  14. Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells.

    PubMed

    Jumnongprakhon, Pichaya; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

    2016-09-01

    Melatonin is a neurohormone and has high potent of antioxidant that is widely reported to be active against methamphetamine (METH)-induced toxicity to neuron, glial cells, and brain endothelial cells. However, the role of melatonin on the inflammatory responses which are mostly caused by blood-brain barrier (BBB) impairment by METH administration has not been investigated. This study used the primary rat brain microvascular endothelial cells (BMVECs) to determine the protective mechanism of melatonin on METH-induced inflammatory responses in the BBB via nuclear factor-ĸB (NF-κB) and nuclear factor erythroid 2-related factor-2 (Nrf2) signaling. Herein, we demonstrated that melatonin reduced the level of the inflammatory mediators, including intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, matrix metallopeptidase (MMP)-9, inducible nitric oxide synthase (iNOS), and nitric oxide (NO) caused by METH. These responses were related to the decrease of the expression and translocation of the NF-κB p65 subunit and the activity of NADPH oxidase (NOX)-2. In addition, melatonin promoted the antioxidant processes, modulated the expression and translocation of Nrf2, and also increased the level of heme oxygenase (HO)-1, NAD (P) H: quinone oxidoreductase (NQO)-1, γ-glutamylcysteine synthase (γ-GCLC), and the activity of superoxide dismutase (SOD) through NOX2 mechanism. In addition, we found that the protective role of melatonin in METH-induced inflammatory responses in the BBB was mediated through melatonin receptors (MT1/2). We concluded that the interaction of melatonin with its receptor prevented METH-induced inflammatory responses by suppressing the NF-κB signaling and promoting the Nrf2 signaling before BBB impairment. PMID:27268413

  15. Melatonin and derived l-tryptophan metabolites produced during alcoholic fermentation by different wine yeast strains.

    PubMed

    Fernández-Cruz, E; Álvarez-Fernández, M A; Valero, E; Troncoso, A M; García-Parrilla, M C

    2017-02-15

    Melatonin is a neurohormone involved in the regulation of circadian rhythms in humans. Evidence has recently been found of its occurrence in wines and its role in the winemaking process. The yeast Saccharomyces cerevisiae is consequently thought to be important in Melatonin synthesis, but limited data and reference texts are available on this synthetic pathway. This paper aims to elucidate whether the synthetic pathway of Melatonin in Saccharomyces and non-Saccharomyces strains involves these intermediates. To this end, seven commercial strains comprising Saccharomyces cerevisiae (Red Fruit, ES488, Lalvin QA23, Uvaferm BC, and Lalvin ICV GRE) and non-Saccharomyces (Torulaspora delbrueckii and Metschnikowia pulcherrima) were monitored, under controlled fermentation conditions, in synthetic must, for seven days. Samples were analysed using a UHPLC-HRMS system (Qexactive). Five out of the seven strains formed Melatonin during the fermentation process: three S. cerevisiae strains and the two non-Saccharomyces. Additionally, other compounds derived from l-tryptophan occurred during fermentation. PMID:27664655

  16. Melatonin suppresses cerebral edema caused by middle cerebral artery occlusion/reperfusion in rats assessed by magnetic resonance imaging.

    PubMed

    Torii, Kunio; Uneyama, Hisayuki; Nishino, Hitoo; Kondoh, Takashi

    2004-01-01

    Melatonin, a pineal secretory product synthesized from tryptophan, has been found to be effective against neurotoxicity. The present study was aimed at demonstrating the effectiveness of melatonin in vivo in reducing ischemia-induced cerebral edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.) just prior to 1 hr of MCA occlusion and 1 day after the surgery. T2-weighted multislice spin-echo images were acquired 1 day after the surgery. In the saline-treated control rats, increases in T2-weighted signals (water content) were clearly observed in the striatum and in the cerebral cortex. In the melatonin-treated group, total volume of edema was reduced by 51.6% compared with control group (P < 0.01). The protective effect of melatonin against edema was more clearly observed in the cerebral cortex (reduced by 59.8%, P < 0.01) than in the striatum (reduced by 34.2%, P < 0.05). Edema volume in a coronal slice was the greatest at the level of the bregma. Suppression of cerebral edema by melatonin was more effective posterior than anterior to the bregma. Melatonin appeared to reduce the volume of the edematous sites rather than to shift the signal intensity distribution. The present MRI study clearly demonstrates the effectiveness of melatonin against cerebral edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments associated with ischemic stroke.

  17. Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma.

    PubMed

    Li, Jun; Wang, Ping; Wang, Bin

    2016-05-01

    Pineal metastasis is uncommon and most metastatic pineal lesions are asymptomatic. To our knowledge the herein reported case is the first in which the pineal gland was confirmed as the metastatic site of a bladder carcinoma.The patient reported in this case is a 59-year-old man who suffered from headache and delirium for 4 days after surgical treatment for removal of a bladder carcinoma 1 year ago. Magnetic resonance imaging (MRI) revealed a solid tumor involving the pineal gland with significant enhancement.The patient underwent surgical treatment for removal of the neoplastic lesion in the pineal gland. Histopathological examination confirmed invasion of the pineal gland by metastatic urothelial carcinoma.This case highlighted that the presence of pineal lesions in patient with known malignancy should raise suspicion of metastatic involvement.

  18. Unique Case Report of Pineal Gland Metastasis From Bladder Carcinoma

    PubMed Central

    Li, Jun; Wang, Ping; Wang, Bin

    2016-01-01

    Abstract Pineal metastasis is uncommon and most metastatic pineal lesions are asymptomatic. To our knowledge the herein reported case is the first in which the pineal gland was confirmed as the metastatic site of a bladder carcinoma. The patient reported in this case is a 59-year-old man who suffered from headache and delirium for 4 days after surgical treatment for removal of a bladder carcinoma 1 year ago. Magnetic resonance imaging (MRI) revealed a solid tumor involving the pineal gland with significant enhancement. The patient underwent surgical treatment for removal of the neoplastic lesion in the pineal gland. Histopathological examination confirmed invasion of the pineal gland by metastatic urothelial carcinoma. This case highlighted that the presence of pineal lesions in patient with known malignancy should raise suspicion of metastatic involvement. PMID:27149501

  19. Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans

    PubMed Central

    Rajaratnam, Shantha M W; Middleton, Benita; Stone, Barbara M; Arendt, Josephine; Dijk, Derk-Jan

    2004-01-01

    The rhythm of plasma melatonin originating from the pineal gland and driven by the circadian pacemaker located in the suprachiasmatic nucleus is closely associated with the circadian (approximately 24 h) variation in sleep propensity and sleep spindle activity in humans. We investigated the contribution of melatonin to variation in sleep propensity, structure, duration and EEG activity in a protocol in which sleep was scheduled to begin during the biological day, i.e. when endogenous melatonin concentrations are low. The two 14 day trials were conducted in an environmental scheduling facility. Each trial included two circadian phase assessments, baseline sleep and nine 16 h sleep opportunities (16.00–08.00 h) in near darkness. Eight healthy male volunteers (24.4 ± 4.4 years) without sleep complaints were recruited, and melatonin (1.5 mg) or placebo was administered at the start of the first eight 16 h sleep opportunities. During melatonin treatment, sleep in the first 8 h of the 16 h sleep opportunities was increased by 2 h. Sleep per 16 h was not significantly different and approached asymptotic values of 8.7 h in both conditions. The percentage of rapid eye movement (REM) sleep was not affected by melatonin, but the percentage of stage 2 sleep and sleep spindle activity increased, and the percentage of stage 3 sleep decreased. During the washout night, the melatonin-induced advance in sleep timing persisted, but was smaller than on the preceding treatment night and was consistent with the advance in the endogenous melatonin rhythm. These data demonstrate robust, direct sleep-facilitating and circadian effects of melatonin without concomitant changes in sleep duration, and support the use of melatonin in the treatment of sleep disorders in which the circadian melatonin rhythm is delayed relative to desired sleep time. PMID:15459246

  20. Melatonin Improves Mitochondrial Function by Promoting MT1/SIRT1/PGC-1 Alpha-Dependent Mitochondrial Biogenesis in Cadmium-Induced Hepatotoxicity In Vitro

    PubMed Central

    Guo, Pan; Pi, Huifeng; Xu, Shangcheng; Zhang, Lei; Li, Yuming; Li, Min; Cao, Zhengwang; Tian, Li; Xie, Jia; Li, Renyan; He, Mindi; Lu, Yonghui; Liu, Chuan; Duan, Weixia; Yu, Zhengping; Zhou, Zhou

    2014-01-01

    Melatonin is an indolamine synthesized in the pineal gland that has a wide range of physiological functions, and it has been under clinical investigation for expanded applications. Increasing evidence demonstrates that melatonin can ameliorate cadmium-induced hepatotoxicity. However, the potentially protective effects of melatonin against cadmium-induced hepatotoxicity and the underlying mechanisms of this protection remain unclear. This study investigates the protective effects of melatonin pretreatment on cadmium-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. We exposed HepG2 cells to different concentrations of cadmium chloride (2.5, 5, and 10μM) for 12 h. We found that Cd stimulated cytotoxicity, disrupted the mitochondrial membrane potential, increased reactive oxygen species production, and decreased mitochondrial mass and mitochondrial DNA content. Consistent with this finding, Cd exposure was associated with decreased Sirtuin 1 (SIRT1) protein expression and activity, thus promoted acetylation of PGC-1 alpha, a key enzyme involved in mitochondrial biogenesis and function, although Cd did not disrupt the interaction between SIRT1 and PGC-1 alpha. However, all cadmium-induced mitochondrial oxidative injuries were efficiently attenuated by melatonin pretreatment. Moreover, Sirtinol and SIRT1 siRNA each blocked the melatonin-mediated elevation in mitochondrial function by inhibiting SIRT1/ PGC-1 alpha signaling. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to promote SIRT1/ PGC-1 alpha signaling. In summary, our results indicate that SIRT1 plays an essential role in the ability of moderate melatonin to stimulate PGC-1 alpha and improve mitochondrial biogenesis and function at least partially through melatonin receptors in cadmium-induced hepatotoxicity. PMID:25159133

  1. Developmental and light-entrained expression of melatonin and its relationship to the circadian clock in the sea anemone Nematostella vectensis

    PubMed Central

    2014-01-01

    Background The primary hormone of the vertebrate pineal gland, melatonin, has been identified broadly throughout the eukaryotes. While the role for melatonin in cyclic behavior via interactions with the circadian clock has only been reported in vertebrates, comparative research has shown that the transcription-translation loops of the animal circadian clock likely date to the cnidarian-bilaterian ancestor, leaving open significant questions about the evolutionary origin of melatonin signaling in circadian behavior by interacting with the molecular clock. Results Expression of melatonin in adult anemones showed peak expression at the end of light period (zeitgeber time (ZT) = 12) when cultured under diel conditions, coinciding with expression of genes and enzyme activity for members of the melatonin synthesis pathway (tryptophan hydroxylase and hydroxyindol-O-methyltransferase), which also showed rhythmic expression. During embryogenesis and juvenile stages, melatonin showed cyclic oscillations in concentration, peaking in midday. Spatial (in situ hybridization) and quantitative (real-time PCR) transcription of clock genes during development of N. vectensis showed these ‘clock’ genes are expressed early in the development, prior to rhythmic oscillations, suggesting functions independent of a function in the circadian clock. Finally, time-course studies revealed that animals transferred from diel conditions to constant darkness lose circadian expression for most of the clock genes within 4 days, which can be reset by melatonin supplementation. Conclusions Our results support an ancient role for melatonin in the circadian behavior of animals by showing cyclic expression of this hormone under diel conditions, light-dependent oscillations in genes in the melatonin synthesis pathway, and the function of melatonin in initiating expression of circadian clock genes in the cnidarian N. vectensis. The differences in expression melatonin and the circadian clock gene

  2. Relation between residential magnetic fields, light-at-night, and nocturnal urine melatonin levels in women: Volume 1 -- Background and purpose, methods, results, discussion. Final report

    SciTech Connect

    Kaune, W.; Davis, S.; Stevens, R.

    1997-11-01

    Scientists have postulated a link between exposure to magnetic fields and reduced blood melatonin levels. This EPRI study was designed to supplement a National Cancer Institute study (NCI-BC) of magnetic fields, light-at-night, and the risk of breast cancer. By expanding the exposure assessment of the NCI-BC and collecting data on urine melatonin levels, this project provides new insight into a possible magnetic field-melatonin link. It has been proposed that exposure to 60-Hz (power frequency) magnetic fields may increase the risk of breast cancer by suppressing the normal nocturnal rise in melatonin production in the pineal gland. It remains unknown whether the human pineal gland is reproducibly responsive or sensitive to magnetic field exposure, and whether such exposures could alter elements of the endogenous hormonal environment in women that might be important in the etiology of breast cancer. The objective of this research was to investigate whether exposure to power-frequency magnetic fields and/or light-at-night is associated with levels of the primary urinary melatonin metabolite in women without a history of breast cancer.

  3. Relation between residential magnetic fields, light-at-night, and nocturnal urine melatonin levels in women: Volume 2 -- Magnetic field exposure analysis. Final report

    SciTech Connect

    Kaune, W.; Davis, S.; Stevens, R.

    1997-11-01

    Scientists have postulated a link between exposure to magnetic fields and reduced blood melatonin levels. This EPRI study was designed to supplement a National Cancer Institute study (NCI-BC) of magnetic fields, light-at-night, and the risk of breast cancer. By expanding the exposure assessment of the NCI-BC and collecting data on urine melatonin levels, this project provides new insight into a possible magnetic field-melatonin link. It has been proposed that exposure to 60-Hz (power frequency) magnetic fields may increase the risk of breast cancer by suppressing the normal nocturnal rise in melatonin production in the pineal gland. It remains unknown whether the human pineal gland is reproducibly responsive or sensitive to magnetic field exposure, and whether such exposures could alter elements of the endogenous hormonal environment in women that might be important in the etiology of breast cancer. The objective of this research was to investigate whether exposure to power-frequency magnetic fields and/or light-at-night is associated with levels of the primary urinary melatonin metabolite in women without a history of breast cancer.

  4. The daily melatonin pattern in Djungarian hamsters depends on the circadian phenotype.

    PubMed

    Schöttner, Konrad; Simonneaux, Valérie; Vuillez, Patrick; Steinlechner, Stephan; Pévet, Paul; Weinert, Dietmar

    2011-12-01

    Djungarian hamsters (Phodopus sungorus) bred at the Institute of Halle reveal three different circadian phenotypes. The wild type (WT) shows normal locomotor activity patterns, whereas in hamsters of the DAO (delayed activity onset) type, the activity onset is continuously delayed. Since the activity offset in those hamsters remains coupled to "light-on," the activity time becomes compressed. Hamsters of the AR (arrhythmic) type are episodically active throughout the 24 h. Previous studies showed that a disturbed interaction of the circadian system with the light-dark (LD) cycle contributes to the phenomenon observed in DAO hamsters. To gain better insight into the underlying mechanisms, the authors investigated the daily melatonin rhythm, as it is a reliable marker of the circadian clock. Hamsters were kept individually under standardized laboratory conditions (LD 14:10, T=22°C±2°C, food and water ad libitum). WT, DAO (with exactly 5 h delay of activity onset), and AR hamsters were used for pineal melatonin and urinary 6-sulfatoxymelatonin (aMT6s) measurement. Pineal melatonin content was determined at 3 time points: 4 h after "light-off" [D+4], 1 h before "light-on" [L-1], and 1h after "light-on" [L+1]). The 24-h profile of melatonin secretion was investigated by transferring the animals to metabolic cages for 27?h to collect urine at 3-h intervals for aMT6s analysis. WT hamsters showed high pineal melatonin content during the dark time (D+4, L-1), which significantly decreased at the beginning of the light period (L+1). In contrast, DAO hamsters displayed low melatonin levels during the part of the dark period when animals were still resting (D+4). At the end of the dark period (L-1), melatonin content increased significantly and declined again when light was switched on (L+1). AR hamsters showed low melatonin levels, comparable to daytime values, at all 3 time points. The results were confirmed by aMT6s data. WT hamsters showed a marked circadian pattern of

  5. Glutamate Transporter-Mediated Glutamate Secretion in the Mammalian Pineal Gland

    PubMed Central

    Kim, Mean-Hwan; Uehara, Shunsuke; Muroyama, Akiko; Hille, Bertil; Moriyama, Yoshinori; Koh, Duk-Su

    2008-01-01

    Glutamate transporters are expressed throughout the central nervous system where their major role is to clear released glutamate from presynaptic terminals. Here we report a novel function of the transporter in rat pinealocytes. This electrogenic transporter conducted inward current in response to L-glutamate and L- or D-aspartate and depolarized the membrane in patch clamp experiments. Ca2+ imaging demonstrated that the transporter-mediated depolarization induced a significant Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ rise finally evoked glutamate exocytosis as detected by carbon-fiber amperometry and by high-performance liquid chromatography. In pineal slices with densely packed pinealocytes, glutamate released from the cells effectively activated glutamate transporters in neighboring cells. The Ca2+ signal generated by KCl depolarization or acetylcholine propagated through several cell layers by virtue of the regenerative ‘glutamate-induced glutamate release’. Therefore we suggest that glutamate transporters mediate synchronized elevation of L-glutamate and thereby efficiently down-regulate melatonin secretion via previously identified inhibitory metabotropic glutamate receptors in the pineal gland. PMID:18945893

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

    PubMed

    Haldar, C; Guchhait, P

    2000-07-01

    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.

  7. Day and Night GSH and MDA Levels in Healthy Adults and Effects of Different Doses of Melatonin on These Parameters.

    PubMed

    Chakravarty, Shilpa; Rizvi, Syed Ibrahim

    2011-01-01

    The pineal secretory product melatonin (chemically, N-acetyl-5-methoxytryptamine) acts as an effective antioxidant and free-radical scavenger and plays an important role in several physiological functions such as sleep induction, immunomodulation, cardiovascular protection, thermoregulation, neuroprotection, tumor-suppression and oncostasis. Membrane lipid-peroxidation in terms of malondialdehyde (MDA) and intracellular glutathione (GSH) is considered to be a reliable marker of oxidative stress. The present work was undertaken to study the modulating effect of melatonin on MDA and GSH in human erythrocytes during day and night. Our observation shows the modulation of these two biomarkers by melatonin, and this may have important therapeutic implications. In vitro dose-dependent effect of melatonin also showed variation during day and night. We explain our observations on the basis of melatonin's antioxidative function and its effect on the fluidity of plasma membrane of red blood cells. Rhythmic modulation of MDA and GSH contents emphasized the role of melatonin as an antioxidant and its function against oxidative stress.

  8. Mapping of the gene for the Mel{sub 1a}-melatonin receptor to human chromosome 4 (MTNR1A) and mouse chromosome 8 (Mtnr1a)

    SciTech Connect

    Slaugenhaupt, S.A. |; Liebert, C.B.; Altherr, M.R.

    1995-05-20

    The pineal hormone melatonin elicits potent circadian and reproductive effects in mammals. The authors report the chromosomal location of the gene for the Mel{sub 1a}-melatonin receptor that likely mediates these circadian and reproductive actions. PCR analysis of human-rodent somatic cell hybrids showed that the receptor gene (MTNR1A) maps to human chromosome 4q35.1. An interspecific backcross analysis revealed that the mouse gene (Mtnr1a) maps to the proximal portion of chromosome 8. These loci may be involved in genetically based circadian and neuroendocrine disorders. 14 refs., 1 fig.

  9. POTENTIAL USE OF MELATONIN IN PROCEDURAL ANXIETY AND PAIN IN CHILDREN UNDERGOING BLOOD WITHDRAWAL.

    PubMed

    Marseglia, L; Manti, S; D'Angelo, G; Arrigo, T; Cuppari, C; Salpietro, C; Gitto, E

    2015-01-01

    The recognition of the value of pain, especially in the pediatric population, has increased over the last decade. It is known that pain-related anxiety can increase perceived pain intensity. There are several different approaches to the treatment of pre-procedural anxiety and procedural pain in children. Melatonin, a neurohormone with the profile of a novel hypnotic-anaesthetic agent, plays an important role in anxiolysis and analgesia. This study investigated the effects of oral melatonin premedication to reduce anxiety and pain in children having blood samples taken. The investigations were carried out on 60 children, aged 1-14 years, divided into 2 equal groups. Using a computer-generated randomization schedule, patients were given either melatonin orally (0.5 mg/kg BW, max 5 mg) or placebo 30 min before blood draw. Pre-procedural anxiety was assessed using the scale from the Children’s Anxiety and Pain Scales, while procedural pain used the Face, Legs, Activity, Cry and Consolability assessment tool for children under the age of 3 years, Faces Pain Scale-Revised for children aged 3-8 years and Numeric Rating Scale for children over the age of 8 years. Oral administration of melatonin before the blood withdrawal procedure significantly reduced both anxiety (p<0.0005) and pain levels than placebo (p<0.0002 for children under 3 years and p<0.0039 for children over 3 years). These data support the use of melatonin for taking blood samples due to its anxiolytic and analgesic properties. Further studies are needed to support the routine use of melatonin to alleviate anxiety and pain in pediatric patients having blood samples taken.

  10. Subthreshold Concentrations of Melatonin and Galantamine Improves Pathological AD-Hallmarks in Hippocampal Organotypic Cultures.

    PubMed

    Buendia, I; Parada, E; Navarro, E; León, R; Negredo, P; Egea, J; López, M G

    2016-07-01

    Melatonin is a neurohormone whose levels are significantly reduced or absent in Alzheimer's disease (AD) patients. In these patients, acetylcholinesterase inhibitors (AChEI) are the major drug class used for their treatment; however, they present unwanted cholinergic side effects and have provided limited efficacy in clinic. Because combination therapy is being extensively used to treat different pathological diseases such as cancer or acquired immune deficiency syndrome, we posed this study to evaluate if melatonin in combination with an AChEI, galantamine, could provide beneficial properties in a novel in vitro model of AD. Thus, we subjected organotypic hippocampal cultures (OHCs) to subtoxic concentrations of β-amyloid (0.5 μM βA) plus okadaic acid (1 nM OA), for 4 days. This treatment increased by 95 % cell death, which was mainly apoptotic as shown by positive TUNEL staining. In addition, the combination of βA/OA increased Thioflavin S aggregates, hyperphosphorylation of Tau, oxidative stress (increased DCFDA fluorescence), and neuroinflammation (increased IL-1β and TNFα). Under these experimental conditions, melatonin (1-1000 nM) and galantamine (10-1000 nM), co-incubated with the toxic stimuli, caused a concentration-dependent neuroprotection; maximal neuroprotective effect was achieved at 1 μM of melatonin and galantamine. Most effective was the finding that combination of sub-effective concentrations of melatonin (1 nM) and galantamine (10 nM) provided a synergic anti-apoptotic effect and reduction of most of the AD-related pathological hallmarks observed in the βA/OA model. Therefore, we suggest that supplementation of melatonin in combination with lower doses of AChEIs could be an interesting strategy for AD patients. PMID:26081146

  11. Effects of melatonin on DNA damage induced by cyclophosphamide in rats

    PubMed Central

    Ferreira, S.G.; Peliciari-Garcia, R.A.; Takahashi-Hyodo, S.A.; Rodrigues, A.C.; Amaral, F.G.; Berra, C.M.; Bordin, S.; Curi, R.; Cipolla-Neto, J.

    2013-01-01

    The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy. PMID:23471360

  12. Melatonin reduces cerebral edema formation caused by transient forebrain ischemia in rats.

    PubMed

    Kondoh, Takashi; Uneyama, Hisayuki; Nishino, Hitoo; Torii, Kunio

    2002-12-20

    Reduction of cerebral edema, an early symptom of ischemia, is one of the most important remedies for reducing subsequent chronic neural damage in stroke. Melatonin, a metabolite of tryptophan released from the pineal gland, has been found to be effective against neurotoxicity in vitro. The present study was aimed to demonstrate the effectiveness of melatonin in vivo in reducing ischemia-induced edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.): just prior to 1 h MCA occlusion and 1 day after the surgery. T2-weighted multislice spin-echo images were acquired 1 day after the surgery. Increases in T2-weighted signals in ischemic sites of the brain were clearly observed after MCA occlusion. The signal increase was found mainly in the striatum and in the cerebral cortex in saline-treated control rats. In the melatonin-treated group, the total volume of cerebral edema was reduced by 45.3% compared to control group (P < 0.01). The protective effect of melatonin against cerebral edema was more clearly observed in the cerebral cortex (reduced by 56.1%, P < 0.01), while the reduction of edema volume in the striatum was weak (reduced by 23.0%). The present MRI study clearly demonstrated that melatonin is effective in reducing edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments.

  13. Melatonin Activates Endoplasmic Reticulum Stress and Apoptosis in Rats with Diethylnitrosamine-Induced Hepatocarcinogenesis

    PubMed Central

    Moreira, Andrea Janz; Ordoñez, Raquel; Cerski, Carlos Thadeu; Picada, Jaqueline Nascimento; García-Palomo, Andrés; Marroni, Norma Possa; Mauriz, Jose L.; González-Gallego, Javier

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most lethal human cancers worldwide because of its high incidence, its metastatic potential and the low efficacy of conventional treatment. Inactivation of apoptosis is implicated in tumour progression and chemotherapy resistance, and has been linked to the presence of endoplasmic reticulum stress. Melatonin, the main product of the pineal gland, exerts anti-proliferative, pro-apoptotic and anti-angiogenic effects in HCC cells, but these effects still need to be confirmed in animal models. Male Wistar rats in treatment groups received diethylnitrosamine (DEN) 50 mg/kg intraperitoneally twice/once a week for 18 weeks. Melatonin was given in drinking water at 1 mg/kg/d, beginning 5 or 12 weeks after the start of DEN administration. Melatonin improved survival rates and successfully attenuated liver injury, as shown by histopathology, decreased levels of serum transaminases and reduced expression of placental glutathione S-transferase. Furthermore, melatonin treatment resulted in a significant increase of caspase 3, 8 and 9 activities, polyadenosine diphosphate (ADP) ribose polymerase (PARP) cleavage, and Bcl-associated X protein (Bax)/Bcl-2 ratio. Cytochrome c, p53 and Fas-L protein concentration were also significantly enhanced by melatonin. Melatonin induced an increased expression of activating transcription factor 6 (ATF6), C/EBP-homologous protein (CHOP) and immunoglobulin heavy chain-binding protein (BiP), while cyclooxygenase (COX)-2 expression decreased. Data obtained suggest that induction of apoptosis and ER stress contribute to the beneficial effects of melatonin in rats with DEN-induced HCC. PMID:26656265

  14. Melatonin concentrations in the sudden infant death syndrome

    NASA Technical Reports Server (NTRS)

    Sturner, W. Q.; Lynch, H. J.; Deng, M. H.; Gleason, R. E.; Wurtman, R. J.

    1990-01-01

    To examine a possible relationship between pineal function and the sudden infant death syndrome (SIDS), samples of whole blood, ventricular cerebrospinal fluid (CSF) and/or vitreous humor (VH) were obtained at autopsy from 68 infants (45 male, 23 female) whose deaths were attributed to either SIDS (n = 32, 0.5-5.0 months of age; mean plus or minus S.E.M., 2.6 plus or minus 0.2 months) or other causes (non-SIDS, n = 36, 0.3-8.0 months of age 4.3 plus or minus 0.3 months). The melatonin concentrations were measured by radioimmunoassay. A significant correlation was observed for melatonin levels in different body fluids from the same individual. After adjusting for age differences, CSF melatonin levels were significantly lower among the SIDS infants (91 plus or minus 29 pmol/l; n = 32) than among those dying from other causes (180 plus or minus 27; n = 35, P less than 0.05). A similar, but non-significant trend was also noted in blood (97 plus or minus 23, n = 30 vs. 144 plus or minus 22 pmol/l, n = 33) and vitreous humor (68 plus or minus 21, n = 10 vs. 81 plus or minus 17 pmol/l, n = 15). These differences do not appear to be explainable in terms of the interval between death and autopsy, gender, premortem infection, or therapeutic measures instituted prior to death. Diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.

  15. Endodermal cyst in pineal region: Rare location

    PubMed Central

    Lopez-Gonzalez, Miguel Angel; Dolan, Eugen

    2016-01-01

    Background: Pineal tumors are very uncommon intracranial lesions, and endodermal cysts in this location are extremely rare. Case Description: A 49-year-old right-handed female presented with 3 weeks history of progressive dizziness and imbalance. Imaging studies showed 1.8 cm × 1.7 cm × 1.8 cm pineal lesion with small enhancing mural component displacing ventrally the quadrigeminal plate and narrowing of aqueduct of Sylvius without hydrocephalus. In addition, she was found with small interhemispheric lipoma, and small posterior falx possible meningioma. Cerebrospinal fluid markers obtained by lumbar puncture were all negative. She underwent tumor resection, and final pathology reported endodermal cyst. No new deficits were encountered, and her gait imbalance improved significantly by 3 months follow-up. Conclusions: With evidence of enlargement or symptomatic pineal lesions, surgical consideration is necessary. Among pineal lesions, endodermal cysts are extremely uncommon and although benign pathology, long-term follow-up is advised due to unknown chronic behavior. PMID:27217965

  16. Human melatonin in magnetic fields: Second study. Final report

    SciTech Connect

    Graham, C.; Cook, M.R.; Cohen, H.D.

    1995-11-01

    Melatonin (MLT) is a hormone secreted primarily at night by the pineal gland in the brain. A number of studies suggest it is part of the body`s natural defenses against cancer. This hormone is reported to stimulate immune function and has been implicated in the control of cell proliferation, the growth of transplanted tumors, and the promotion and/or co-promotion of mammary tumors. MLT also plays a key role in the regulation of reproductive hormones implicated in a number of carcinogenic processes. Studies with rodents, although not always consistent, suggest that nocturnal MLT levels may be suppressed by electric or magnetic field (EMF) exposure. This relationship has been proposed as a possible biological mechanism to account for epidemiological reports linking chronic EMF exposure and increased cancer risk. Research was needed to determine if a similar suppression of MLT occurs when humans are exposed to magnetic fields at night.

  17. Symptomatic glial cysts of the pineal gland.

    PubMed

    Fain, J S; Tomlinson, F H; Scheithauer, B W; Parisi, J E; Fletcher, G P; Kelly, P J; Miller, G M

    1994-03-01

    Small asymptomatic cysts of the pineal gland represent a common incidental finding in adults undergoing computerized tomography or magnetic resonance (MR) imaging or at postmortem examination. In contrast, large symptomatic pineal cysts are rare, being limited to individual case reports or small series. The authors have reviewed 24 cases of large pineal cysts. The mean patient age at presentation was 28.7 years (range 15 to 46 years); 18 were female and six male. Presenting features in 20 symptomatic cases included: headache in 19; nausea and/or vomiting in seven; papilledema in five; visual disturbances in five (diplopia in three, "blurred vision" in two, and unilateral partial oculomotor nerve palsy in one); Parinaud's syndrome in two; hemiparesis in one; hemisensory aberration in one; and seizures in one. Four lesions were discovered incidentally. Magnetic resonance imaging typically demonstrated a 0.8- to 3.0-cm diameter mass (mean 1.7 cm) with homogeneous decreased signal intensity on T1-weighted images, increased signal intensity on T2-weighted images, and a distinct margin. Hydrocephalus was present in eight cases. The cysts were surgically excised via an infratentorial/supracerebellar approach (23 cases) or stereotactically biopsied (one case). Histological examination revealed a cyst wall 0.5 to 2.0 mm thick comprised of three layers: an outer fibrous layer, a middle layer of pineal parenchymal cells with variable calcification, and an inner layer of hypocellular glial tissue often exhibiting Rosenthal fibers and/or granular bodies. Evidence of prior hemorrhage, mild astrocytic degenerative atypia, and disorganization of pineal parenchyma were often present. Postoperative follow-up review in all 24 cases (range 3 months to 10 years) revealed no complications in 21, mild ocular movement deficit in one, gradually resolving Parinaud's syndrome in one, and radiographic evidence of a postoperative venous infarct of the superior cerebellum with ataxia of 1 week

  18. Cytologic features of the normal pineal gland on squash preparations.

    PubMed

    Murro, Diana; Alsadi, Alaa; Nag, Sukriti; Arvanitis, Leonidas; Gattuso, Paolo

    2014-11-01

    As primary pineal lesions are extremely rare, many surgical pathologists are unfamiliar with normal pineal cytologic features. We describe cytologic features of the normal pineal gland in patients of varying ages and identify common diagnostic pitfalls. We performed a retrospective review of pineal gland biopsies performed at our institution, where approximately 30,000 surgical specimens are accessioned yearly, for the last 23 years. Only two pineal gland biopsies were found. Although both cases were initially diagnosed as low-grade gliomas on frozen section, the final diagnosis was benign pineal tissue based on light microscopy and immunohistochemistry results. Additionally, we performed squash preparations of five normal pineal gland autopsy specimens with Papanicolaou and Diff-Quik® (Dade Behring, Newark, DE) stains. Infant preparations were highly cellular smears composed of numerous, uniform, single cells with indistinct cytoplasm, small round-to-oval nuclei, fine chromatin, and absent nucleoli and calcifications. The vague microfollicular pattern mimicked a pineocytoma and the fine fibrillary background mimicked a glial neoplasm. Young adult smears were similar; however, microcalcifications were present with fewer background single cells. Older patients had much less cellular smears composed of small clusters of cells with fusiform-to-spindle nuclei, a fine chromatin pattern, and indistinct cytoplasmic borders. There were fewer background single cells and more microcalcifications. The cytologic features of the native pineal gland vary with age. Normal pineal tissue can be confused with a pineocytoma or low-grade glioma. Familiarity with normal pineal gland cytological features will help to avoid a potential misdiagnosis.

  19. The Gordon Wilson Lecture: Neurohormonal Signaling Pathways That Link Cardiac Growth and Death

    PubMed Central

    Dorn, Gerald W.

    2007-01-01

    Far from being a simple muscular pump, the heart senses changes in hemodynamic forces and neurohormonal signaling, and responds by elaborating autocrine and paracrine factors that self-regulate cardiomyocyte contraction, growth, and programmed death. Interference with the afferent or efferent arms of this stress-response mechanism, as with inhibition of the β-adrenergic or renin/angiotensin systems, is a mainstay of pharmacological therapy for heart failure. However, despite striking group-mean effects showing mortality benefits of neurohormonal antagonists, inter-individual variability in the therapeutic response to these agents suggests a pharmacogenomic interaction, where common sequence variations of genes that regulate neurohormonal signaling modify the individual response to treatment. Furthermore, there is increasing evidence that, depending upon physiological milieu, conventional neurohormone receptor-ligand pairs can activate non-traditional signaling pathways, with pathological consequences. Recently, studies that integrate the findings from human gene polymorphism discovery, recombinant gene variant expression in cell and animal models, and outcome or risk analysis of polymorphisms in human disease have provided additional understanding into adaptive and maladaptive events that are the consequence of the cardiac stress-response sequence. PMID:18528498

  20. Phosphodiesterase 10A in the rat pineal gland: localization, daily and seasonal regulation of expression and influence on signal transduction.

    PubMed

    Spiwoks-Becker, Isabella; Wolloscheck, Tanja; Rickes, Oliver; Kelleher, Debra K; Rohleder, Nils; Weyer, Veronika; Spessert, Rainer

    2011-01-01

    The cyclic nucleotide phosphodiesterase 10A (PDE10A) is highly expressed in striatal spiny projection neurons and represents a therapeutic target for the treatment of psychotic symptoms. As reported previously [J Biol Chem 2009; 284:7606-7622], in this study PDE10A was seen to be additionally expressed in the pineal gland where the levels of PDE10A transcript display daily changes. As with the transcript, the amount of PDE10A protein was found to be under daily and seasonal regulation. The observed cyclicity in the amount of PDE10A mRNA persists under constant darkness, is blocked by constant light and is modulated by the lighting regime. It therefore appears to be driven by the master clock in the suprachiasmatic nucleus (SCN). Since adrenergic agonists and dibutyryl-cAMP induce PDE10A mRNA, the in vitro clock-dependent control of Pde10a appears to be mediated via a norepinephrine → β-adrenoceptor → cAMP/protein kinase A signaling pathway. With regard to the physiological role of PDE10A in the pineal gland, the specific PDE10A inhibitor papaverine was seen to enhance the adrenergic stimulation of the second messenger cAMP and cGMP. This indicates that PDE10A downregulates adrenergic cAMP and cGMP signaling by decreasing the half-life of both nucleotides. Consistent with its effect on cAMP, PDE10A inhibition also amplifies adrenergic induction of the cAMP-inducible gene arylalkylamine N-acetyltransferase (Aanat) which codes the rate-limiting enzyme in pineal melatonin formation. The findings of this study suggest that Pde10a expression is under circadian and seasonal regulation and plays a modulatory role in pineal signal transduction and gene expression.

  1. Review of Disrupted Sleep Patterns in Smith-Magenis Syndrome and Normal Melatonin Secretion in a Patient with an Atypical Interstitial 17p11.2 Deletion

    PubMed Central

    Boudreau, Eilis A.; Johnson, Kyle P.; Jackman, Angela R.; Blancato, Jan; Huizing, Marjan; Bendavid, Claude; Jones, MaryPat; Chandrasekharappa, Settara C.; Lewy, Alfred J.; Smith, Ann C. M.; Magenis, R. Ellen

    2009-01-01

    Smith-Magenis syndrome (SMS) is a disorder characterized by multiple congenital anomalies and behavior problems, including abnormal sleep patterns. It is most commonly due to a 3.5 Mb interstitial deletion of chromosome 17 band p11.2. Secretion of melatonin, a hormone produced by the pineal gland, is the body’s signal for nighttime darkness. Published reports of 24-hour melatonin secretion patterns in two independent SMS cohorts (US & France) document an inverted endogenous melatonin pattern in virtually all cases (96%), suggesting that this finding is pathognomic for the syndrome. We report on a woman with SMS due to an atypical large proximal deletion (∼6Mb; cen<->TNFRSFproteinB) of chromosome band (17)(p11.1p11.2) who presents with typical sleep disturbances but a normal pattern of melatonin secretion. We further describe a melatonin light suppression test in this patient. This is the second reported patient with a normal endogenous melatonin rhythm in SMS associated with an atypical large deletion. These two patients are significant because they suggest that the sleep disturbances in SMS cannot be solely attributed to the abnormal diurnal melatonin secretion versus the normal nocturnal pattern. PMID:19530184

  2. The melatonin-sensitive circadian clock of the enteric bacterium Enterobacter aerogenes.

    PubMed

    Paulose, Jiffin K; Cassone, Vincent M

    2016-09-01

    Circadian clocks are fundamental properties of all eukaryotic organisms and at least some prokaryotic organisms. Recent studies in our laboratory have shown that the gastrointestinal system contains a circadian clock that controls many, if not all, aspects of gastrointestinal function. We now report that at least one species of intestinal bacteria, Enterobacter aerogenes, responds to the pineal and gastrointestinal hormone melatonin by an increase in swarming activity. This swarming behavior is expressed rhythmically, with a period of approximately 24 hrs. Transformation of E. aerogenes to express luciferase with a MotA promoter reveals circadian patterns of bioluminescence that are synchronized by melatonin and whose periods are temperature compensated from 26°C to 40°C. Bioinformatics suggest similarities between the E. aerogenes and cyanobacterial clocks, suggesting the circadian clock may have evolved very early in the evolution of life. They also point to a coordination of host circadian clocks with those residing in the microbiota themselves. PMID:27387841

  3. [The circadian system in man: From the internal clock to melatonin secretion].

    PubMed

    Touitou, Y

    2016-09-01

    The internal or biological clock which is located in the suprachiasmatic nuclei of the anterior hypothalamus is controlled by clock genes and environmental factors which are able to synchronize the clock to 24h. Rhythm desynchronization (shiftwork and nightwork, transmeridian flights, aging, some psychiatric diseases, blindness, intake of some drugs…) occurs when the internal clock does no longer work in harmony with the astronomical time i.e. our watch. The circadian system consists of three major elements, which are the clock, the retinohypothalamic tract and melatonin which is secreted by the pineal gland and considered as the arrow of the clock. Both light and melatonin present a phase response curve useful for the treatment of sleep circadian disorders.

  4. The melatonin-sensitive circadian clock of the enteric bacterium Enterobacter aerogenes.

    PubMed

    Paulose, Jiffin K; Cassone, Vincent M

    2016-09-01

    Circadian clocks are fundamental properties of all eukaryotic organisms and at least some prokaryotic organisms. Recent studies in our laboratory have shown that the gastrointestinal system contains a circadian clock that controls many, if not all, aspects of gastrointestinal function. We now report that at least one species of intestinal bacteria, Enterobacter aerogenes, responds to the pineal and gastrointestinal hormone melatonin by an increase in swarming activity. This swarming behavior is expressed rhythmically, with a period of approximately 24 hrs. Transformation of E. aerogenes to express luciferase with a MotA promoter reveals circadian patterns of bioluminescence that are synchronized by melatonin and whose periods are temperature compensated from 26°C to 40°C. Bioinformatics suggest similarities between the E. aerogenes and cyanobacterial clocks, suggesting the circadian clock may have evolved very early in the evolution of life. They also point to a coordination of host circadian clocks with those residing in the microbiota themselves.

  5. Supplementation of Slow-Release Melatonin Improves Recovery of Ovarian Cyclicity and Conception in Summer Anoestrous Buffaloes (Bubalus bubalis).

    PubMed

    Kumar, A; Mehrotra, S; Singh, G; Maurya, V P; Narayanan, K; Mahla, A S; Chaudhari, R K; Singh, M; Soni, Y K; Kumawat, B L; Dabas, S K; Srivastava, N

    2016-02-01

    The role of melatonin as a protective neurohormone against restoring cyclicity in summer anoestrous animals in photoperiod species has gained wider acceptance. This study was designed to uncover the evidence the slow-release melatonin (MLT) has on initiation of ovarian cyclicity and conception rate (CR) in summer anoestrous buffaloes. Thus, buffaloes diagnosed as summer anoestrous (absence of overt signs of oestrus, concurrent rectal examination and radioimmunoassay for serum progesterone at 10 days interval) were grouped as untreated (Group I, sterilized corn oil, n = 8) and treated (Group II, single subcutaneous injection of MLT @18 mg/50 kg bwt in sterilized corn oil, n = 20). Animals treated and detected in oestrus were artificially inseminated (AI) followed by division into Group III (second dose of MLT on 5th day post-AI, n = 8) and Group IV (no melatonin administration, n = 10). Blood samples were collected at 4 days interval for estimation of serum MLT, progesterone and oestrogen using radioimmunoassay kit. Mean oestrous induction rate (OIR), oestrous induction interval (OII), interoestrous interval (IOI) and CR were estimated. Compared to control, concentration of melatonin was significantly (p < 0.05) higher in treated group ranging from 14.34 ± 1.72 to 412.31 ± 14.47 pg/ml whereas other two hormones did not show any concentration difference. Melatonin-administered buffaloes showed significantly (p < 0.05) higher (90%) OIR with OII of 18.06 ± 1.57 days. Results showed improvement in conception rate in buffaloes administered with post-insemination melatonin. It can be concluded from the study that slow-release melatonin supplementation restored cyclicity in summer anoestrous animals resulting in improvement in conception rate in buffaloes.

  6. Melatonin Signal Transduction Pathways Require E-Box-Mediated Transcription of Per1 and Per2 to Reset the SCN Clock at Dusk

    PubMed Central

    Kandalepas, Patty C.; Mitchell, Jennifer W.; Gillette, Martha U.

    2016-01-01

    Melatonin is released from the pineal gland into the circulatory system at night in the absence of light, acting as “hormone of darkness” to the brain and body. Melatonin also can regulate circadian phasing of the suprachiasmatic nucleus (SCN). During the day-to-night transition, melatonin exposure advances intrinsic SCN neural activity rhythms via the melatonin type-2 (MT2) receptor and downstream activation of protein kinase C (PKC). The effects of melatonin on SCN phasing have not been linked to daily changes in the expression of core genes that constitute the molecular framework of the circadian clock. Using real-time RT-PCR, we found that melatonin induces an increase in the expression of two clock genes, Period 1 (Per1) and Period 2 (Per2). This effect occurs at CT 10, when melatonin advances SCN phase, but not at CT 6, when it does not. Using anti-sense oligodeoxynucleotides (α ODNs) to Per 1 and Per 2, as well as to E-box enhancer sequences in the promoters of these genes, we show that their specific induction is necessary for the phase-altering effects of melatonin on SCN neural activity rhythms in the rat. These effects of melatonin on Per1 and Per2 were mediated by PKC. This is unlike day-active non-photic signals that reset the SCN clock by non-PCK signal transduction mechanisms and by decreasing Per1 expression. Rather, this finding extends roles for Per1 and Per2, which are critical to photic phase-resetting, to a nonphotic zeitgeber, melatonin, and suggest that the regulation of these clock gene transcripts is required for clock resetting by diverse regulatory cues. PMID:27362940

  7. Long noncoding RNA H19 mediates melatonin inhibition of premature senescence of c-kit(+) cardiac progenitor cells by promoting miR-675.

    PubMed

    Cai, Benzhi; Ma, Wenya; Bi, Chongwei; Yang, Fan; Zhang, Lai; Han, Zhenbo; Huang, Qi; Ding, Fengzhi; Li, Yuan; Yan, Gege; Pan, Zhenwei; Yang, Baofeng; Lu, Yanjie

    2016-08-01

    Melatonin, a hormone secreted by the pineal gland, possesses multiple biological activities such as antitumor, antioxidant, and anti-ischemia. C-kit(+) cardiac progenitor cells (CPCs) have emerged as a promising tool for the treatment of heart diseases. However, the senescence of CPCs due to pathological stimuli leads to the decline of CPCs' functions and regenerative potential. This study was conducted to demonstrate whether melatonin antagonizes the senescence of CPCs in response to oxidative stress. Here, we found that the melatonin treatment markedly inhibited the senescent characteristics of CPCs after exposed to sublethal concentration of H2 O2 , including the increase in senescence-associated β-galactosidase (SA-β-gal)-positive CPCs, senescence-associated heterochromatin loci (SAHF), secretory IL-6 level, and the upregulation of p53 and p21 proteins. Senescence-associated proliferation reduction was also attenuated by melatonin in CPCs. Luzindole, the melatonin membrane receptor blocker, may block the melatonin-mediated suppression of premature senescence in CPCs. Interestingly, we found that long noncoding RNA H19 and its derived miR-675 were downregulated by H2 O2 in CPCs, but melatonin treatment could counter this alteration. Furthermore, knockdown of H19 or miR-675 blocked antisenescence actions of melatonin on H2 O2 -treated CPCs. It was further verified that H19-derived miR-675 targeted at the 3'UTR of USP10, which resulted in the downregulation of p53 and p21 proteins. In summary, melatonin antagonized premature senescence of CPCs via H19/miR-675/USP10 pathway, which provides new insights into pharmacological actions and potential applications of melatonin on the senescence of CPCs.

  8. Measurement of Serum Melatonin in Intensive Care Unit Patients: Changes in Traumatic Brain Injury, Trauma, and Medical Conditions

    PubMed Central

    Seifman, Marc A.; Gomes, Keith; Nguyen, Phuong N.; Bailey, Michael; Rosenfeld, Jeffrey V.; Cooper, David J.; Morganti-Kossmann, Maria Cristina

    2014-01-01

    Melatonin is an endogenous hormone mainly produced by the pineal gland whose dysfunction leads to abnormal sleeping patterns. Changes in melatonin have been reported in acute traumatic brain injury (TBI); however, the impact of environmental conditions typical of the intensive care unit (ICU) has not been assessed. The aim of this study was to compare daily melatonin production in three patient populations treated at the ICU to differentiate the role of TBI versus ICU conditions. Forty-five patients were recruited and divided into severe TBI, trauma without TBI, medical conditions without trauma, and compared to healthy volunteers. Serum melatonin levels were measured at four daily intervals at 0400 h, 1000 h, 1600 h, and 2200 h for 7 days post-ICU admission by commercial enzyme linked immunosorbent assay. The geometric mean concentrations (95% confidence intervals) of melatonin in these groups showed no difference being 8.3 (6.3–11.0), 9.3 (7.0–12.3), and 8.9 (6.6–11.9) pg/mL, respectively, in TBI, trauma, and intensive care cohorts. All of these patient groups demonstrated decreased melatonin concentrations when compared to control patients. This study suggests that TBI as well as ICU conditions, may have a role in the dysfunction of melatonin. Monitoring and possibly substituting melatonin acutely in these settings may assist in ameliorating long-term sleep dysfunction in all of these groups, and possibly contribute to reducing secondary brain injury in severe TBI. PMID:25477861

  9. Endogenous melatonin provides an effective circadian message to both the suprachiasmatic nuclei and the pars tuberalis of the rat.

    PubMed

    Agez, Laurence; Laurent, Virginie; Guerrero, Hilda Y; Pévet, Paul; Masson-Pévet, Mireille; Gauer, François

    2009-01-01

    The suprachiasmatic nuclei (SCN) distribute the circadian neural message to the pineal gland which transforms it into a humoral circadian message, the nocturnal melatonin synthesis, which in turn modulates tissues expressing melatonin receptors such as the SCN or the pars tuberalis (PT). Nuclear orphan receptors (NOR), including rorbeta and rev-erbalpha, have been presented as functional links between the positive and negative loops of the molecular clock. Recent findings suggest that these NOR could be the initial targets of melatonin's chronobiotic message within the SCN. We investigated the role of these NOR in the physiological effect of endogenous melatonin on these tissues. We monitored rorbeta and rev-erbalpha mRNA expression levels by quantitative in situ hybridization after pinealectomy. Pinealectomy had no effect on NOR circadian expression rhythms in the SCN in 8-day pinealectomized (PX) animals. However in animals PX for 3 months, significant desynchronization between per1 and per2 transcription patterns appeared. These results suggest that endogenous melatonin could sustain the circadian rhythmicity and the phase relationship between the molecular partners of the SCN circadian system on a long-term basis. On the other hand, pinealectomy decreased the level and abolished the rhythmicity of NOR mRNA expression in the PT. These effects were partially prevented by daily melatonin administration in the drinking water. These results show that NOR can be regulated by the melatonin circadian rhythm in the PT and could be the link between the physiological action of melatonin and the core of the molecular circadian clock in this tissue.

  10. [Consensus document on the clinical use of melatonin in children and adolescents with sleep-onset insomnia].

    PubMed

    Pin Arboledas, G; Merino Andreu, M; de la Calle Cabrera, T; Hidalgo Vicario, M I; Rodríguez Hernández, P J; Soto Insuga, V; Madrid Pérez, J A

    2014-11-01

    Sleep problems are highly prevalent among our children and adolescents. Its treatment is mainly based on cognitive behavioural therapies and habit modification procedures. However, the use of sleep promoting drugs and substances is widespread without being supported by clinical guidelines. Exogenous melatonin is a neurohormone marketed as a nutritional supplement that is being increasingly used in the management of sleep problems, and with no control over its use. The consensus document is presented on the use of melatonin in sleep-onset insomnia prepared by representatives of the Spanish Paediatric Association, the Spanish Society of Sleep, the Spanish Society of Paediatric Outpatients and Primary Care, the Spanish Society for Adolescent Medicine, the Spanish Society of Child Psychiatry, and the Spanish Society of Paediatric Neurology.

  11. [Consensus document on the clinical use of melatonin in children and adolescents with sleep-onset insomnia].

    PubMed

    Pin Arboledas, G; Merino Andreu, M; de la Calle Cabrera, T; Hidalgo Vicario, M I; Rodríguez Hernández, P J; Soto Insuga, V; Madrid Pérez, J A

    2014-11-01

    Sleep problems are highly prevalent among our children and adolescents. Its treatment is mainly based on cognitive behavioural therapies and habit modification procedures. However, the use of sleep promoting drugs and substances is widespread without being supported by clinical guidelines. Exogenous melatonin is a neurohormone marketed as a nutritional supplement that is being increasingly used in the management of sleep problems, and with no control over its use. The consensus document is presented on the use of melatonin in sleep-onset insomnia prepared by representatives of the Spanish Paediatric Association, the Spanish Society of Sleep, the Spanish Society of Paediatric Outpatients and Primary Care, the Spanish Society for Adolescent Medicine, the Spanish Society of Child Psychiatry, and the Spanish Society of Paediatric Neurology. PMID:24768501

  12. Pineal Gland Lymphoma: Case Report and Literature Review.

    PubMed

    Gupta, Akshya; Johnson, Mahlon; Hussain, Ali

    2015-01-01

    A 65-year-old male presented to our institution with acute-onset headache. Imaging studies demonstrated a mass in the region of the pineal gland, with subsequent histopathology findings being consistent with large B cell lymphoma. The patient was treated with methotrexate, but ultimately did not survive. Primary central nervous system (CNS) lymphoma rarely involves the pineal gland, but should be considered in the differential diagnosis of pineal gland tumors in the appropriate clinical setting.

  13. Pineal Gland Lymphoma: Case Report and Literature Review

    PubMed Central

    Gupta, Akshya; Johnson, Mahlon; Hussain, Ali

    2015-01-01

    A 65-year-old male presented to our institution with acute-onset headache. Imaging studies demonstrated a mass in the region of the pineal gland, with subsequent histopathology findings being consistent with large B cell lymphoma. The patient was treated with methotrexate, but ultimately did not survive. Primary central nervous system (CNS) lymphoma rarely involves the pineal gland, but should be considered in the differential diagnosis of pineal gland tumors in the appropriate clinical setting. PMID:26605125

  14. [Participation of pineal gland in antistressor activity of adaptogenic drugs].

    PubMed

    Arushanian, É B; Beĭer, É V

    2015-01-01

    Chronic stress produces some morphological changes in rats, including thymus weight reduction, adrenal hypertrophy, and peptic ulcers in stomach. Repeated administration of phytoadaptogenic drugs (ginseng and bilobil) decreased these stress-induced disorders. The antistressor activity of drugs was attenuated upon by removal of the pineal gland. Histochemical and morphometric investigation of pineal tissues in stressed animals showed that that the pharmacological effect was accompanied by increasing functional activity of the pineal gland. It is suggested that pineal mobilization may participate in antistressor activity of phytoadaptogenic drugs.

  15. Pineal region tumors: computed tomographic-pathologic spectrum

    SciTech Connect

    Futrell, N.N.; Osborn, A.G.; Cheson. B.D.

    1981-11-01

    While several computed tomographic (CT) studies of posterior third ventricular neoplasms have included descriptions of pineal tumors, few reports have concentrated on these uncommon lesions. Some authors have asserted that the CT appearance of many pineal tumors is virtually pathognomonic. A series of nine biopsy-proved pineal gland and eight other presumed tumors is presented that illustrates their remarkable heterogeneity in both histopathologic and CT appearance. These tumors included germinomas, teratocarcinomas, hamartomas, and other varieties. They had variable margination, attentuation, calcification, and suprasellar extension. Germinomas have the best response to radiation therapy. Biopsy of pineal region tumors is now feasible and is recommended for treatment planning.

  16. The prevalence of pineal cyst in patients with cerebral palsy

    PubMed Central

    Özmen, Evrim; Derinkuyu, Betül; Samancı, Cesur; Ünlü, Havva Akmaz; Demirkan, Tülin Hakan; Haşıloğlu, Zehra Işık; Kuruoğlu, Sebuh; Adaletli, İbrahim

    2015-01-01

    PURPOSE Pineal cysts are common incidental findings during magnetic resonance imaging (MRI) examinations. The etiology of pineal cyst development is still unclear. We aimed to determine whether there is an association between periventricular leukomalacia and pineal cyst prevalence. METHODS Clinical and MRI data of 201 patients with periventricular leukomalacia (110 female, 91 male; mean age, 6 years; range, 2–18 years) and 687 control patients (355 female, 332 male; mean age, 6 years¸ range, 2–18 years) who did not have any evidence of periventricular leukomalacia were independently evaluated by two radiologists for presence or absence of pineal cyst. RESULTS Pineal cysts were detected in 32.3% of the study group (65/201) and 8.4% of the control group (58/687) (P < 0.001). Patients with periventricular leukomalacia were more likely to have a pineal cyst. In terms of pineal cyst detection on MRI, interobserver reliability was high between the two radiologists. CONCLUSION The prevalence of pineal cysts is higher in patients with periventricular leukomalacia. We suggest that an ischemic process may have a role in the etiopathogenesis of pineal cyst development. PMID:25858521

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

    PubMed

    Finger, S

    1995-01-01

    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. PMID:11619024

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

    PubMed

    Finger, S

    1995-01-01

    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.

  19. [Participation of pineal gland in antistressor activity of adaptogenic drugs].

    PubMed

    Arushanian, É B; Beĭer, É V

    2015-01-01

    Chronic stress produces some morphological changes in rats, including thymus weight reduction, adrenal hypertrophy, and peptic ulcers in stomach. Repeated administration of phytoadaptogenic drugs (ginseng and bilobil) decreased these stress-induced disorders. The antistressor activity of drugs was attenuated upon by removal of the pineal gland. Histochemical and morphometric investigation of pineal tissues in stressed animals showed that that the pharmacological effect was accompanied by increasing functional activity of the pineal gland. It is suggested that pineal mobilization may participate in antistressor activity of phytoadaptogenic drugs. PMID:25826867

  20. Melatonin: Buffering the Immune System

    PubMed Central

    Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

    2013-01-01

    Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

  1. Short-wavelength enrichment of polychromatic light enhances human melatonin suppression potency.

    PubMed

    Brainard, George C; Hanifin, John P; Warfield, Benjamin; Stone, Marielle K; James, Mary E; Ayers, Melissa; Kubey, Alan; Byrne, Brenda; Rollag, Mark

    2015-04-01

    The basic goal of this research is to determine the best combination of light wavelengths for use as a lighting countermeasure for circadian and sleep disruption during space exploration, as well as for individuals living on Earth. Action spectra employing monochromatic light and selected monochromatic wavelength comparisons have shown that short-wavelength visible light in the blue-appearing portion of the spectrum is most potent for neuroendocrine, circadian, and neurobehavioral regulation. The studies presented here tested the hypothesis that broad spectrum, polychromatic fluorescent light enriched in the short-wavelength portion of the visible spectrum is more potent for pineal melatonin suppression in healthy men and women. A total of 24 subjects were tested across three separate experiments. Each experiment used a within-subjects study design that tested eight volunteers to establish the full-range fluence-response relationship between corneal light irradiance and nocturnal plasma melatonin suppression. Each experiment tested one of the three types of fluorescent lamps that differed in their relative emission of light in the short-wavelength end of the visible spectrum between 400 and 500 nm. A hazard analysis, based on national and international eye safety criteria, determined that all light exposures used in this study were safe. Each fluence-response curve demonstrated that increasing corneal irradiances of light evoked progressively increasing suppression of nocturnal melatonin. Comparison of these fluence-response curves supports the hypothesis that polychromatic fluorescent light is more potent for melatonin regulation when enriched in the short-wavelength spectrum.

  2. NMR and molecular dynamics studies of the interaction of melatonin with calmodulin

    PubMed Central

    Turjanski, Adrián G.; Estrin, Darío A.; Rosenstein, Ruth E.; McCormick, John E.; Martin, Stephen R.; Pastore, Annalisa; Biekofsky, Rodolfo R.; Martorana, Vincenzo

    2004-01-01

    Pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is thought to modulate the calcium/calmodulin signaling pathway either by changing intracellular Ca2+ concentration via activation of its G-protein–coupled membrane receptors, or through a direct interaction with calmodulin (CaM). The present work studies the direct interaction of melatonin with intact calcium-saturated CaM both experimentally, by fluorescence and nuclear magnetic resonance spectroscopies, and theoretically, by molecular dynamics simulations. The analysis of the experimental data shows that the interaction is calcium-dependent. The affinity, as obtained from monitoring 15N and 1H chemical shift changes for a melatonin titration, is weak (in the millimolar range) and comparable for the N- and C-terminal domains. Partial replacement of diamagnetic Ca2+ by paramagnetic Tb3+ allowed the measurement of interdomain NMR pseudocontact shifts and residual dipolar couplings, indicating that each domain movement in the complex is not correlated with the other one. Molecular dynamics simulations allow us to follow the dynamics of melatonin in the binding pocket of CaM. Overall, this study provides an example of how a combination of experimental and theoretical approaches can shed light on a weakly interacting system of biological and pharmacological significance. PMID:15498938

  3. Influence of Melatonin on the Immune System of Fish: A Review

    PubMed Central

    Esteban, M. Ángeles; Cuesta, Alberto; Chaves-Pozo, Elena; Meseguer, José

    2013-01-01

    Endocrine-immune system interactions have been widely demonstrated in mammals, whereas in fish, these relationships remain unclear. Of the organs that constitute the endocrine system, the pineal gland and its secretory product melatonin act in the synchronization of daily and seasonal rhythms in most vertebrates, including fish. Seasonal differences in immunocompetence and disease prevalence have been well documented in humans. Seasonality also strongly influences the life history of fish by controlling the timing of physiological events, such as reproduction, food intake, locomotor activity, and growth performance. Apart from its synchronizing capabilities, the role of melatonin in physiological processes in fish is not thoroughly understood. The purpose of this review is to summarize current studies on the effects of melatonin on the fish immune system. These studies suggest that melatonin represents an important component of fish endocrine-immune system interactions. The elucidation of the defense mechanisms of fish will facilitate the development of health management tools to support the growing finfish aquaculture industry as well as address questions concerning the origins and evolution of the immune system in vertebrates. PMID:23579958

  4. Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

    NASA Technical Reports Server (NTRS)

    Zeitzer, J. M.; Ayas, N. T.; Shea, S. A.; Brown, R.; Czeisler, C. A.

    2000-01-01

    The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

  5. Role of Melatonin in Traumatic Brain Injury and Spinal Cord Injury

    PubMed Central

    Naseem, Mehar; Parvez, Suhel

    2014-01-01

    Brain and spinal cord are implicated in incidences of two of the most severe injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a devastating neurological deficit involving primary and secondary injury cascades. The primary and secondary mechanisms include complex consequences of activation of proinflammatory cytokines, cerebral edema, upregulation of NF-κβ, disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury (SCI) includes primary and secondary injury cascades. Primary injury leads to secondary injury in which generation of free radicals and oxidative or nitrative damage play an important pathophysiological role. The indoleamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. It has a special characteristic of crossing BBB. Melatonin has neuroprotective role in the injured part of the CNS after TBI and SCI. A number of studies have successfully shown its therapeutic value as a neuroprotective agent in the treatment of neurodegenerative diseases. Here in this review we have compiled the literature supporting consequences of CNS injuries, TBI and SCI, and the protective role of melatonin in it. PMID:25587567

  6. Genetic deletion of MT₁/MT₂ melatonin receptors enhances murine cognitive and motor performance.

    PubMed

    O'Neal-Moffitt, G; Pilli, J; Kumar, S S; Olcese, J

    2014-09-26

    Melatonin, an indoleamine hormone secreted into circulation at night primarily by the brain's pineal gland, has been shown to have a wide variety of actions on the development and physiology of neurons in the CNS. Acting via two G-protein-coupled membrane receptors (MT1 and MT2), melatonin modulates neurogenesis, synaptic functions, neuronal cytoskeleton and gene expression. In the present studies, we sought to characterize the behavior and neuronal biology of transgenic mice lacking both of these melatonin receptors as a way to understand the hormone's receptor versus non-receptor-mediated actions in CNS-dependent activities, such as learning and memory, anxiety, general motor performance and circadian rhythmicity. Assessment of these behaviors was complemented by molecular analyses of gene expression in the brain. Our results demonstrate mild behavioral hyperactivity and a lengthened circadian period of free-running motor activity in melatonin receptor-deficient mice as compared to receptor-intact control mice beginning at an early age. Significant improvement in cognitive performance was found using the Barnes Maze and the Y-Maze. No behavioral changes in anxiety levels were found. Electrophysiological measures in hippocampal slices revealed a clear enhancement of long-term potentiation in mice lacking melatonin receptors with no significant differences in paired-pulse facilitation. Quantitative analysis of brain protein expression levels of phosphoCREB and phosphoERK1/2 and key markers of synaptic activity (synapsin, glutamate receptor 1, spinophilin, and glutamic acid decarboxylase 1) revealed significant differences between the double-knockout and wild-type animals, consistent with the behavioral findings. Thus, genetic deletion of melatonin receptors produces mice with enhanced cognitive and motor performance, supporting the view that these receptors play an important role in neurobehavioral development.

  7. Combination of Pitavastatin and melatonin shows partial antineoplastic effects in a rat breast carcinoma model.

    PubMed

    Kubatka, Peter; Bojková, Bianka; Kassayová, Monika; Orendáš, Peter; Kajo, Karol; Výbohová, Desanka; Kružliak, Peter; Adamicová, Katarína; Péč, Martin; Stollárová, Nadežda; Adamkov, Marián

    2014-10-01

    Our previous results indicated significant tumor-suppressive effects of different statins in rat mammary carcinogenesis. The purpose of this experiment was to examine the chemopreventive effects of Pitavastatin alone and in combination with the pineal hormone melatonin in the model of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female Sprague-Dawley rats. Pitavastatin was administered dietary (10mg/kg) and melatonin in an aqueous solution (20μg/ml). Chemoprevention began 7 days prior to carcinogen administration and subsequently continued for 15 weeks until autopsy. At autopsy, mammary tumors were removed and prepared for histopathological and immunohistochemical analysis. Compared to controls, Pitavastatin alone reduced average tumor volume by 58% and lengthened latency by 8 days; on the other hand, the drug increased tumor frequency by 23%. Combined administration of Pitavastatin with melatonin decreased tumor frequency by 23%, tumor volume by 44% and lengthened tumor latency by 5.5 days compared to control animals. The analysis of carcinoma cells showed significant increase in caspase-3 expression in both treated groups and a tendency of increased caspase-7 expression after Pitavastatin treatment alone. Significant expression decrease of Ki67 was found in carcinoma cells from both treated groups. Compared to control carcinoma cells, Pitavastatin alone increased VEGF expression by 41%, however melatonin totally reversed its undesirable effect. Pitavastatin combined with melatonin significantly increased femur compact bone thickness in animals. Pitavastatin alone decreased plasma triglycerides and total cholesterol levels, however it significantly increased levels of glucose. In summary, our results show a partial antineoplastic effect of Pitavastatin combined with melatonin in the rat mammary gland carcinoma model. PMID:25450902

  8. The role of the pineal gland in the photoperiodic control of bird song frequency and repertoire in the house sparrow, Passer domesticus.

    PubMed

    Wang, Gang; Harpole, Clifford E; Paulose, Jiffin; Cassone, Vincent M

    2014-04-01

    Temperate zone birds are highly seasonal in many aspects of their physiology. In mammals, but not in birds, the pineal gland is an important component regulating seasonal patterns of primary gonadal functions. Pineal melatonin in birds instead affects seasonal changes in brain song control structures, suggesting the pineal gland regulates seasonal song behavior. The present study tests the hypothesis that the pineal gland transduces photoperiodic information to the control of seasonal song behavior to synchronize this important behavior to the appropriate phenology. House sparrows, Passer domesticus, expressed a rich array of vocalizations ranging from calls to multisyllabic songs and motifs of songs that varied under a regimen of different photoperiodic conditions that were simulated at different times of year. Control (SHAM) birds exhibited increases in song behavior when they were experimentally transferred from short days, simulating winter, to equinoctial and long days, simulating summer, and decreased vocalization when they were transferred back to short days. When maintained in long days for longer periods, the birds became reproductively photorefractory as measured by the yellowing of the birds' bills; however, song behavior persisted in the SHAM birds, suggesting a dissociation of reproduction from the song functions. Pinealectomized (PINX) birds expressed larger, more rapid increases in daily vocal rate and song repertoire size than did the SHAM birds during the long summer days. These increases gradually declined upon the extension of the long days and did not respond to the transfer to short days as was observed in the SHAM birds, suggesting that the pineal gland conveys photoperiodic information to the vocal control system, which in turn regulates song behavior.

  9. Primary Malignant Melanoma in the Pineal Region

    PubMed Central

    Hong, Yong-Kil

    2014-01-01

    A 59-year-old male patient had 5-month history of gait disturbance and memory impairment. His initial brain computed tomography scan showed 3.5×2.8 cm sized mass with high density in the pineal region. The tumor was hypointense on T2 weighted magnetic resonance images and hyperintense on T1 weighted magnetic resonance images with heterogenous enhancement of central portion. The tumor was totally removed via the occipital transtentorial approach. Black mass was observed in the operation field, and after surgery, histopathological examination confirmed the diagnosis of malignant melanoma. Whole spine magnetic resonance images and whole body 18-fluoro-deoxyglucose positron emission tomography could not demonstrate the primary site of this melanoma. Scrupulous physical examination of his skin and mucosa was done and dark pigmented lesion on his left leg was found, but additional studies including magnetic resonance images and skin biopsy showed negative finding. As a result, final diagnosis of primary pineal malignant melanoma was made. He underwent treatment with the whole brain radiotherapy and extended local boost irradiation without chemotherapy. His preoperative symptoms were disappeared, and no other specific neurological deficits were founded. His follow-up image studies showed no recurrence or distant metastasis until 26 weeks after surgery. Primary pineal malignant melanomas are extremely rare intracranial tumors, and only 17 cases have been reported since 1899. The most recent case report showed favorable outcome by subtotal tumor resection followed by whole brain and extended local irradiation without chemotherapy. Our case is another result to prove that total tumor resection with radiotherapy can be the current optimal treatment for primary malignant melanoma in the pineal region. PMID:25628812

  10. [Primary teratocarcinoma of the pineal region].

    PubMed

    Masini, T; Tarocchi, A; Cappricci, E; Gullotta, F

    1989-01-01

    Primary Teratocarcinoma of Pineal Region. A case of a 12 year old boy admitted for intracranial hypertension of sudden onset has been reported. CT scanning and MR showed a triventricular hydrocephalus due to a space-occupying lesion of the pineal region. Tonic-clonic fits of the upper limbs and Parinaud syndrome were followed by loss of consciousness. Intervention I: ventriculo-peritoneal shunt with sampling of CSF and assay for beta-HCG, alpha FP and CEA, which proved negative. Cytology for neoplastic cells in cerebrospinal fluid was negative. Intervention II: grossly total removal of the tumor. This was followed by partial remission of Parinaud syndrome, total remission of the hypertensive symptoms and discharge on day 12. The 3 cm. whitish-pink tumor of rubbery consistency proved on histological examination to be a teratocarcinoma. The patient was further submitted to chemioterapy and irradiation but died 7 months after the second intervention. This is a rare tumor, much more than teratoma of the pineal gland, which is relatively frequent. It is interesting histologically because of the presence not only of chondroid and mesenchymal portions but also of adamantinomatous rudiments and of epithelial zones resembling embryonal carcinoma of the testis.

  11. Neuroendoscopic management of pineal region tumours.

    PubMed

    Ferrer, E; Santamarta, D; Garcia-Fructuoso, G; Caral, L; Rumià, J

    1997-01-01

    The management of pineal tumours remains controversial. During 1994 we treated four consecutive adults (16-44 yrs) harbouring a pineal tumour with a neuroendoscopic procedure. All of them presented with hydrocephalus. Pre-operative workup included cranial computerized tomography (CT), craniospinal magnetic resonance imaging (MRI) and serum levels of biological tumour markers. The endoscopic procedure consisted of a third ventriculostomy followed by biopsy with a flexible, steerable neuroendoscope. Histological diagnosis was achieved in three patients who no longer required a shunt device. Recorded complications were: bleeding during ventriculostomy that prevented us from obtaining a good sample for biopsy, short-term memory loss that cleared over a two-week period, and transient increase of pre-operative hemiparesis. Complications and morbidity are emphasized so as to be avoided with further technical experience. Neuroendoscopy affords a minimally invasive way of reaching three objectives by one-step surgery in the management of pineal region lesions: 1) CSF sample for analysis of tumour markers. 2) Treatment of hydrocephalus by third ventriculostomy. 3) Several biopsy specimens can be obtained identifying tumours which will require further open surgery or adjuvant radiation and/or chemotherapy. PMID:9059706

  12. Effect of the photoperiod and administration of melatonin on the pars tuberalis of viscacha (Lagostomus maximus maximus): an ultrastructural study.

    PubMed

    Romera, Edith Perez; Mohamed, Fabian; Fogal, Teresa; Dominguez, Susana; Piezzi, Ramón; Scardapane, Luis

    2010-05-01

    The pituitary pars tuberalis (PT) is a glandular zone exhibiting well-defined structural characteristics. Morphologically, it is formed by specific secretory cells, folliculostellate cells, and migratory cells coming from the pars distalis. The purpose of this work was to investigate differences in specific cellular characteristics in the PT of viscachas captured in summer (long photoperiod) and winter (short photoperiod), as well as the effects of chronic melatonin administration in viscachas captured in summer and kept under long photoperiod. In summer, the PT-specific cells exhibited cell-like characteristics with an important secretory activity and a moderate amount of glycogen. In winter, the PT-specific granulated cells showed ultrastructural variations with signs of a reduced synthesis activity. Also, PT showed a high amount of glycogen and a great number of cells in degeneration. After melatonin administration, the ultrastructural characteristics were similar to those observed in winter, but the amount of glycogen was higher. These results suggest possible functional implications as a result of morphological differences between long and short photoperiods, and are in agreement with the variations of the pituitary-gonadal axis, probably in response to the natural photoperiod changes through the pineal melatonin. The ultrastructural differences observed in PT, after melatonin administration, were similar to those observed in the short photoperiod, thus supporting the hypothesis that these cytological changes are induced by melatonin.

  13. Investigation of Solar about 5-Month Cycle in Human Circulating Melatonin: Signature of Weather in Extraterrestrial Space?

    NASA Astrophysics Data System (ADS)

    Cornélissen, G.; Tarquini, R.; Perfetto, F.; Otsuka, K.; Gigolashvili, M.; Halberg, F.

    2009-12-01

    Melatonin, produced mainly in the pineal and the gut, is often thought of as the "dark hormone" as its concentration in the circulation is high during darkness and low during light in diurnally- and nocturnally-active mammals in health. About-daily and about-yearly periodicities can thus be anticipated to characterize melatonin, matching the two major photic environmental cycles. Non-photic solar influences have also been observed, melatonin being depressed in association with magnetic storms. While less stable than the daily and yearly changes, non-photic solar dynamics also undergo various periodicities. Among them is an about 0.42-year (about 5-month or 154-day) cycle, reported by several physicists in relation to Zürich relative sunspot numbers and to solar flares. This putative signature of solar activity was found in the incidence pattern of sudden cardiac death in Minnesota, USA, among other geographic locations. A cycle with a period of about 0.42 year is here reported in data on circulating melatonin of 172 patients studied between Oct 1992 and Dec 1995 in Florence, Italy. Melatonin may mediate some of the Sun's effects upon the biosphere in certain frequency-windows such as a cis-half-year of about 5 months.

  14. Different neural melatonin-target tissues are critical for encoding and retrieving day length information in Siberian hamsters.

    PubMed

    Teubner, B J W; Freeman, D A

    2007-02-01

    Siberian hamsters exhibit several seasonal rhythms in physiology and behaviour, including reproduction, energy balance, body mass, and pelage colouration. Unambiguous long- and short day lengths stimulate and inhibit reproduction, respectively. Whether gonadal growth or regression occurs in an intermediate day length (e.g. 14 h L : 10 h D; 14L), depends on whether the antecedent day lengths were shorter (10L) or longer (16L). Variations in day length are encoded by the duration of nocturnal pineal melatonin secretion, which is decoded at several neural melatonin target tissues to control testicular structure and function. We assessed participation of three such structures in the acquisition and retrieval of day length information. Elimination of melatonin signalling to the nucleus reuniens (NRe), but not to the suprachiasmatic nucleus (SCN) or paraventricular thalamus (PVt), interfered with the acquisition of a long day reproductive response, whereas the obscuring of melatonin signals to the SCN and the NRe, but not to the PVt, interfered with the photoperiod history response. The SCN and NRe contribute in different ways to the melatonin-based system that mediates seasonal rhythms in male reproduction.

  15. Expression of the melatonin receptor Mel(1c) in neural tissues of the reef fish Siganus guttatus.

    PubMed

    Park, Yong-Ju; Park, Ji-Gweon; Jeong, Hyung-Bok; Takeuchi, Yuki; Kim, Se-Jae; Lee, Young-Don; Takemura, Akihiro

    2007-05-01

    The golden rabbitfish, Siganus guttatus, is a reef fish exhibiting a restricted lunar-related rhythm in behavior and reproduction. Here, to understand the circadian rhythm of this lunar-synchronized spawner, a melatonin receptor subtype-Mel(1c)-was cloned. The full-length Mel(1c) melatonin receptor cDNA comprised 1747 bp with a single open reading frame (1062 bp) that encodes a 353-amino acid protein, which included 7 presumed transmembrane domains. Real-time PCR revealed high Mel(1c) mRNA expression in the retina and brain but not in the peripheral tissues. When the fish were reared under light/dark (LD 12:12) conditions, Mel(1c) mRNA in the retina and brain was expressed with daily variations and increased during nighttime. Similar variations were noted under constant conditions, suggesting that Mel(1c) mRNA expression is regulated by the circadian clock system. Daily variations of Mel(1c) mRNA expression with a peak at zeitgeber time (ZT) 12 were observed in the cultured pineal gland under LD 12:12. Exposure of the cultured pineal gland to light at ZT17 resulted in a decrease in Mel(1c) mRNA expression. When light was obstructed at ZT5, the opposite effect was obtained. These results suggest that light exerts certain effects on Mel(1c) mRNA expression directly or indirectly through melatonin actions.

  16. MT1 melatonin receptors mediate somatic, behavioral, and reproductive neuroendocrine responses to photoperiod and melatonin in Siberian hamsters (Phodopus sungorus).

    PubMed

    Prendergast, Brian J

    2010-02-01

    Environmental day length drives nocturnal pineal melatonin secretion, which in turn generates or entrains seasonal cycles of physiology, reproduction, and behavior. In mammals, melatonin (MEL) binds to a number of receptor subtypes including high-affinity (MT1 and MT2) and low-affinity (MT3, nuclear orphan receptors) binding sites, which are distributed throughout the central nervous system and periphery. The MEL receptors that mediate photoperiodic reproductive and behavioral responses to MEL have not been identified in a reproductively photoperiodic species. Here I tested the hypothesis that MT1 receptors are necessary and sufficient to engage photoperiodic responses by challenging male Siberian hamsters (Phodopus sungorus), a species that does not express functional MT2 receptors, with ramelteon (RAM), a specific MT1/MT2 receptor agonist. In hamsters housed in a long-day photoperiod, late-afternoon RAM treatment inhibited gonadotropin secretion, induced gonadal regression, and suppressed food intake and body mass, mimicking effects of MEL. In addition, chronic (24 h/d) RAM infusions were sufficient to obscure endogenous MEL signaling, and these treatments attenuated gonadal regression in short days. Together, the outcomes indicate that signaling at the MT1 receptor is sufficient and necessary to mediate the effects of photoperiod-driven changes in MEL on behavior and reproductive function in a reproductively photoperiodic mammal.

  17. [MELATONIN CONCENTRATION IN THE BLOOD OF VITILIGO PATIENTS WITH STRESS IN ANAMNESIS].

    PubMed

    Tsiskarishvili, N I; Katsitadze, A; Tsiskarishvili, N V; Tsiskarishvil, Ts; Chitanava, L

    2016-05-01

    In recent years, despite some progress in the study of vitiligo many aspects of pathogenesis and treatment of this dermatosis remain unsolved or are highly controversial. It is believed that progression of disease is associated with a genetic predisposition, autoimmune processes and oxidative stress, but the concrete role of stress on the processes having place in the organism of vitiligo patients so far is not investigated. As we know, epiphysis is the main regulator of adaptation of the individual to the environment. An important product of secretion of the pineal gland is the hormone melatonin - a universal regulator of vital functions and biorhythms of the body. Psychoses, neuroses, depression, immunopathology are aspects of disturbances in circadian, seasonal and annual rhythms of the synthesis of this hormone. Clinical and experimental studies indicate that the hormone melatonin, which is one of the links in a stress defense mechanism of the body, has antioxidant and immunomodulatory properties. The purpose of this study was to determine plasma level of melatonin in the blood of vitiligo patients (with stress in anamnesis), depending on the clinical form and duration of the disease. 41 patients with vitiligo (16 with segmental and 25 with non-segmental form) with stress in anamnesis and duration of disease from several months to 20 years were under observation. The level of melatonin in the blood plasma was determined by ELISA (IBL - international - reagent), the results were expressed in units of pg/ml. According to the results of our study, 8 patients with segmental vitiligo had the normal level of plasma melatonin concentration (in the range of 20.2-31.1 pg/ml), in 2 cases - the level was near the norm (19.2 pg/ml). In the group of patients with non-segmental vitiligo, the level of melatonin was below the norm (12.5 pg/ml) and in 2 cases, the content of melatonin was very low - 4.05 pg / ml. Correlation analysis of melatonin levels with duration of disease

  18. The Role of Melatonin as a Hormone and an Antioxidant in the Control of Fish Reproduction.

    PubMed

    Maitra, Saumen Kumar; Hasan, Kazi Nurul

    2016-01-01

    Reproduction in most fish is seasonal or periodic, and the spawning occurs in an appropriate season to ensure maximum survival of the offspring. The sequence of reproductive events in an annual cycle is largely under the control of a species-specific endogenous timing system, which essentially relies on a well-equipped physiological response mechanism to changing environmental cues. The duration of solar light or photoperiod is one of the most predictable environmental signals used by a large number of animals including fish to coordinate their seasonal breeding. In vertebrates, the pineal gland is the major photoneuroendocrine part of the brain that rhythmically synthesizes and releases melatonin (N-acetyl-5-methoxytryptamine) into the circulation in synchronization with the environmental light-dark cycle. Past few decades witnessed an enormous progress in understanding the mechanisms by which melatonin regulates seasonal reproduction in fish and in other vertebrates. Most studies emphasized hormonal actions of melatonin through its high-affinity, pertussis toxin-sensitive G-protein (guanine nucleotide-binding protein)-coupled receptors on the hypothalamus-pituitary-gonad (HPG) axis of fish. However, the discovery that melatonin due to its lipophilic nature can easily cross the plasma membrane of all cells and may act as a potent scavenger of free radicals and stimulant of different antioxidants added a new dimension to the idea explaining mechanisms of melatonin actions in the regulation of ovarian functions. The basic concept on the actions of melatonin as an antioxidant emerged from mammalian studies. Recently, however, some new studies clearly suggested that melatonin, apart from playing the role of a hormone, may also be associated with the reduction in oxidative stress to augment ovaria