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To perform a single unit review of surgical approaches to the pineal region, looking to ascertain if trends were identifiable regarding the extent of resection and the rate of post-operative complications between approaches. We hypothesised that each approach would offer different exposure of the pineal region which may result in poor access to certain areas of the tumour. This may lead to residual tumour in reliable and predictable locations, and an awareness of these regions could help with pre-operative planning and lead to higher levels of suspicion when inspecting these regions intraoperatively. We performed a single centre, retrospective review of all adult and paediatric patients who underwent surgical debulking of pineal region tumours between 2008 and 2019. Patient demographics, pre- and post- operative radiological tumour volume data, histology and complication rates were compared between the two groups. The occipital transtentorial approach resulted in a significantly lower extent of resection when compared to the supracerebellar infratentorial approach (p = 0.04), even after multivariate analysis (p = 0.006). There was no significant difference between the location of residual tumour relative to the superior colliculi between the two approaches (p = 1.00). There was a significant incidence of radiological occipital lobe ischaemia from the occipital transtentorial approach (p = 0.04). Within our series, we did not demonstrate a consistent location of residual tumour relative to the surgical approach chosen. Whilst there was a significant difference with regards to the extent of resection between approaches, in the context of small comparative groups this is difficult to draw far-reaching conclusions from. [ABSTRACT FROM AUTHOR]

To synchronize with the fluctuating environment, organisms have evolved an endogenous time tracking mechanism referred to as the biological clock(s). This clock machinery has been identified in almost all cells of vertebrates and categorized as central and peripheral clocks. In birds, three independent circadian clocks have been identified in the hypothalamus, the pineal and the retina which interact and generate circadian time at a functional level. However, there is a limited knowledge of molecular clockwork and integration between central and peripheral clocks in birds. Therefore, we studied the daily expression of clock genes (Bmal1, Clock, Per2, Cry1, Npas2, Rev-Erbα, E4bp4, Pparα, Hlf and Tef) in three central circadian clocks (hypothalamus, pineal and retina), other brain areas (cerebellum, optic tectum and telencephalon) and in the peripheral tissues (liver, intestine, muscle and blood) of white-rumped munia. Adult birds were exposed to equinox photoperiod (12 L:12D) for 2 weeks and were then sampled (N = 5 per time point) at six-time points (ZT1, ZT5, ZT9, ZT13, ZT17 and ZT21). Daily expressions of clock genes were studied using qPCR. We observed daily variations and tissue-specific expression patterns for clock genes. These results are consistent with the autoregulatory circadian feedback loop proposed for the mammalian system and thus suggest a conserved tissue-level circadian time generation in white-rumped munia. [ABSTRACT FROM AUTHOR]

Effects of different photoperiods (9L-15D, 12L-12D and 15L-9D at a constant temperature 25 ± 1°C) and simulated temperatures (15°C, 25°C and 35°C under a common photoperiod 12L-12D) were investigated on the circadian rhythms of plasma levels of thyroid hormones [thyroxine (T4) and triiodothyronine (T3)] and pineal arylalkylamine N-acetyltransferase (AANAT) activity in the fish, Clarias gariepinus during winter and summer seasons. Irrespective of the seasons, plasma levels of thyroid hormones (THs) and pineal AANAT activity exhibited circadian rhythm under all the photoperiodic regimes and simulated temperatures. The levels of THs were found to be directly related to the length of photoperiod as well as temperature. In contrast, pineal AANAT activity was inversely related to the length of photoperiod and temperature. On the basis of these findings, we suggest that photoperiod and temperature jointly regulate the inverse temporal relationship between the circadian rhythms of plasma levels of THs and pineal AANAT activity in C. gariepinus. [ABSTRACT FROM AUTHOR]

Arecoline is known to cause endocrine dysfunction. In the current article role of arecoline on pineal–testis activity was investigated in hypothyroid rats induced by propylthiouracil (PTU). PTU treatment caused thyroid dysfunction ultrastructurally with a fall in T3 and T4 levels followed by a rise of thyroid stimulating hormone (TSH) level. Pineal activity was impaired by PTU treatment, as evident from degenerated synaptic ribbons and mitochondria of the pinealocytes with depletion of pineal and serum N-acetyl serotonin and melatonin levels. Leydig cell function was suppressed, evident from reduced smooth endoplasmic reticulum and depletion of testosterone level. Sex accessories function was impaired by showing scanty rough endoplasmic reticulum with depletion of fructose and sialic acid levels. Arecoline treatment that caused pineal dysfunction and testicular stimulation in control rats, suppressed both pineal and testis functions after PTU treatment. The findings suggest that arecoline inhibits pineal–testis function in experimentally induced hypothyroid rats. [ABSTRACT FROM AUTHOR]

Almost all organisms live in a fluctuating environment. To achieve synchrony with the fluctuating environment, organisms have evolved with time-tracking mechanism commonly known as biological clocks. This circadian clock machinery has been identified in almost all cells of vertebrates and categorized as central and peripheral clocks. In birds, three independent circadian clocks reside within the nervous tissues in the hypothalamus, pineal and retina, which interact with each other and produce circadian time at a functional level. There is limited knowledge available of the molecular clockwork, and of integration between central and peripheral clocks in birds. Here, we studied daily expression of canonical clock genes (Bmal1, Clock, Per2, Per3, Cry1 and Cry2) and clock-controlled gene (Npas2) in all three central tissues (hypothalamus, pineal and retina) and in peripheral tissues (liver, intestine and muscle). Wild caught adult male tree sparrows were exposed to equinox photoperiod (12L:12D) for 2 weeks and after that birds were sacrificed (N = 5 per time point) at six time points (ZT1, ZT5, ZT9, ZT13, ZT17 and ZT21; ZT0 is lights on). Daily expression of clock genes was studied using qPCR. Bmal1, Clock, Per2, Per3, Cry1, Cry2 and Npas2 showed daily oscillation in all tissues except Cry2 in hypothalamus, pineal and intestine. We observed tissue-specific expression pattern for all clock and clock-controlled genes. Bmal1 transcripts expressed during early phase of night. Clock acrophase was observed during middle or late day time in the central clock while during early-to-middle phase of night in peripheral tissues. Npas2 expression pattern was similar to Bmal1. Per genes peaked either late at night or early during day time. However, Cry genes were peaked either at late day time (Cry1in retina, liver and intestine; Cry2 in liver and intestine) or at early night phase (Cry1 in hypothalamus, pineal and muscle; Cry2 in hypothalamus, pineal, retina and muscle). Our results are consistent with the autoregulatory circadian feedback loop, and suggest a conserved tissue-level circadian time generation in tree sparrows. Change in peak expression timing of these genes in different tissues implicates tissue-specific contribution of individual clock genes in the circadian time generation. [ABSTRACT FROM AUTHOR]

Plasma levels of thyroid hormones (T4 and T3) and pineal AANAT activity exhibited prominent diurnal rhythms during all the four phases (quiescent, progressive, breeding, and regressive) of the fish, Clarias gariepinus. During all the four phases, we observed that (i) the acrophase (peak) of the circadian rhythm of both T3 and T4 occurred around midday, while the acrophase of AANAT activity rhythm was recorded during midnight, (ii) a significant negative correlation existed between plasma levels of the thyroid hormones and AANAT activity, and (iii) a direct relationship existed between water temperature/daylength and plasma levels of thyroid hormones, and an inverse relationship between water temperature/daylength and AANAT activity. On the basis of these findings, we conclude that an inverse relationship exists between the diurnal rhythms in plasma levels of thyroid hormones and pineal AANAT activity. The observed inverse relationship between the levels of thyroid hormones and pineal AANAT activity seems to be maintained by seasonal changes in water temperature and daylength. [ABSTRACT FROM AUTHOR]

Millions of people consume betel nut for increased capacity to work and for stress reduction. The nut contains arecoline, which has multiple side effects on endocrine functions. Objective of the work is to investigate pineal–testicular responses to noise and after arecoline treatment in noise in rats. Noise exposure (100 dB, 6 h daily, 10 days) caused pineal stimulation ultrastructurally and at indoleamines level. Leydig cell dysfunction with fall of testosterone level and suppression of sex accessories were noticed. In contrast, pineal activity was inhibited and reproductive functions were stimulated after arecoline administration, confirmed from reversed changes to those of noise. Arecoline treatment in noise exposure showed same results as in noise both in pineal and in reproductive functions. It is concluded that noise causes testicular dysfunction probably by gonadotropin suppression induced by pineal melatonin in noise. Furthermore, arecoline cannot prevent it in noise in rats. [ABSTRACT FROM AUTHOR]

Melatonin (N-acetyl-5-methoxy tryptamine), following discovery from the extracts of bovine pineal gland, has been detected in the pineal as well as several extra-pineal tissues/organs of different vertebrates including fish. The unique feature of melatonin in the pineal gland is its rhythmic biosynthesis and release in blood in synchronization with the environmental light-–dark cycle. Accordingly, melatonin produced in the pineal of an animal living in a changing environment is implicated to the regulation of seasonal reproduction by acting as a hormone at one or more levels of hypothalamo-hypophyseal-gonadal axis. Additionally, melatonin is known to act as a potent free-radical scavenger or antioxidant to influence maturation of oocytes. However, possible relationship between extra-pineal melatonin and seasonality of reproduction in any animal remains enigmatic. Perhaps, carp is the only known animal in which temporal patterns of melatonin levels in the serum as well as in the extracts of pineal, retina, ovary, gut, and liver have been studied in relation to the reproductive events in an annual cycle. The purpose of current review is to bring those fascinating, and arguably most important data together to underline their significance in the control of seasonal reproduction in subtropical fish in general and in carp in particular. [ABSTRACT FROM AUTHOR]

The aim of this work was to study the variations in the interference of neuroendocrine pineal gland and metabolically active thyroid gland in a tropical bird, Perdicula asiatica. Maximum pineal gland activity (pineal weight and melatonin level), minimum thyroid gland activity (weight, T3/T4 and thymidine kinase activity) along with less oxidative load (MDA level, SOD, CAT and ABTS activity) were observed during reproductively inactive phase (RIP) was observed. Further, a robust and significant rhythmicity was noted in melatonin levels during RIP and RAP, but no significant rhythmicity was noted in T4/T3 level by cosinor analysis. Overall, melatonin and thyroid circadian profile suggested that melatonin might be acting as an antioxidant molecule with time of the day effect in rescuing thyroid gland from free radical load in birds. [ABSTRACT FROM AUTHOR]

Irisin was first identified in muscle cells. We detected irisin immunoreactivity in various organs of the crested porcupine(Hystrix cristata). In the epidermis, irisin immunoreactivity was localized mainly in stratum basale, stratum spinosum and stratum granulosum layers; immunoreactivity was not observed in the stratum corneum. In the dermis, irisin was found in the external and internal root sheath, cortex and medulla of hair follicles, and in sebaceous glands. Irisin immunoreactivity was found in the neural retina and skeletal muscle fibers associated with the eye. The pineal and thyroid glands also exhibited irisin immunoreactivity. [ABSTRACT FROM AUTHOR]

Depression and biological rhythms disturbances are strongly associated. Agomelatine is an antidepressant with melatoninergic MT1-MT2 agonist and serotoninergic 5-HT2c antagonist properties. Both melatonin and 5-HT are known to modulate circadian rhythmicity controlled by the endogenous clock located in the suprachiasmatic nuclei (SCN). The aim of the present study was to compare the effect of an acute injection of agomelatine (Ago), melatonin (MLT) or an antagonist 5-HT2c (S32006), on the rhythms of two robust clock outputs: the pineal MLT secretion and the body temperature rhythm ( Tc). Daily endogenous MLT profiles were measured using transpineal microdialysis over 4 consecutive days in rats maintained on a 12 h light/12 h dark cycle. Simultaneously, Tc was recorded. The drugs were injected subcutaneously at three doses (1, 2.5 or 5 mg/kg) at the onset of darkness. Both Ago and MLT, at the dose of 2.5 mg/kg, increased the amplitude of the peak of MLT secretion and this effect was observed 2 d after injection. Moreover, both drugs induced a dose-dependent advance of the rhythm onset which resulted in lengthening of the MLT peak. S32006 had no effect on the rhythm of MLT. Ago, MLT and S32006 increased the amplitude of the rhythm of Tc. These data suggest a central action of Ago, directly on the SCN, via melatoninergic receptors responsible for both the increased amplitude of MLT rhythm and the phase advance. The increase in the amplitude of the body temperature could involve both MLT agonist and/or 5-HT2c antagonist properties of Ago. [ABSTRACT FROM AUTHOR]

A temporal relationship between the daily and seasonal profiles of melatonin (N-acetyl-5-methoxytryptamine) in three different parts of gut, pineal, and serum as well as the density of arylalkylamineN-acetyltransferase (AANAT) protein, the key regulator of melatoninergic pathway in the pineal and respective regions of gut has been sought in a tropical carpCatla catlaunder natural photo-thermal conditions. The tissue samples were collected at four different clock hours in a daily cycle and the same was repeated in four different seasons in an annual cycle. In a daily cycle, concentrations of melatonin as well as the band intensity of a ∼23 kDa AANAT protein in each segment of gut, irrespective of sampling months, exhibited a peak at midday, while both the variables in the pineal and melatonin in serum showed a peak either in late dark phase (in March) or at midnight (in the remaining seasons). The simple correlation coefficient analysis of values revealed a negative correlation between the melatoninergic system in the gut and the pineal. Notably, seasonal fluctuations of photoperiod as well as water temperature exhibited a negative correlation with the daily peak values of pineal and serum melatonin, but no significant correlation with the respective values of gut melatonin. In conclusion, attainment of a daily peak in melatonin in the gut, unlike in the pineal and serum, does not seem to be a dark-dependent phenomenon. [ABSTRACT FROM PUBLISHER]

The role of extra-gonadal hormones on the induction of circadian ovarian cycle of the grey mulletMugil cephalusL. was investigated. The findings revealed that thyroid hormones (T3and T4) showed their peak with lowest thyroid stimulating hormone level in pre-spawning, with another peak in April during post-spawning phase. Serum cortisol, epinephrine and norepinephrine concentrations were highest in spawning phase. Insulin level was the highest followed by the lowest blood glucose level in the spawning phase. But, pinealN-acetyl serotonin (NAS) and melatonin (MEL) levels were least with the highest level of serotonin in spawning phase. The findings suggest that (a) T3and T4are involved probably to trigger oocyte growth and vitellogenesis. (b) Whereas, cortisol, epinephrine, norepinephrine and insulin synergistically help to induce final maturation in the spawning phase. (c) Pineal hormonal profiles (NAS and MEL) were reversely altered to those of spawning, indicating negative role of these hormones especially on oocyte growth, vitellogenesis and oocyte maturation in the mullet. Thus, all the extra-gonadal hormones, except pineal, have a role in regulation of circannual ovarian cycle in the flat head grey mullet. [ABSTRACT FROM PUBLISHER]

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 cycle which leads to geomagnetic disturbances and could facilitate seasonal aMT6s rhythmicity during specific years. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

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 (Ca2++) 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 Ca2++ in the pineal revealed stimulatory effects of both adrenergic (α1 and β1) and dopaminergic (D1) 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 α2-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 (α1 and β1, but not α2) and dopaminergic signals are stimulatory, whereas cholinergic signals are inhibitory. This study also provides indications, though arguably not conclusive evidence, that in either case the neuronal mechanisms follow a signal-transduction pathway in which Ca2++ and cAMP may act as the intracellular messengers. It also appears that proteasomal proteolysis is a conserved event in the regulation of AANAT activity in vertebrates. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

Young adult male domestic pigeons were exposed to artificial long photoperiod (LP, 200 watt; 20 hr light, L : 4 hr dark, D), short photoperiod (SP; 4 L : 20 D) and administration of exogenous testosterone propionate (TP) at a daily dose of 1 mg/100 g body weight for 60 consecutive days in primary breeding and regressive phases-I. Administration of TP in LP and SP during primary breeding phase decreased both the adrenal and pineal gland weight. In the TP-LP treatment during breeding phase, adreno-cortical cord width, nuclear diameter of sub-capsular zone (SCZ), central zone (CZ), and pinealocytes decreased significantly. Cholesterol, ascorbic acid level, and side-chain cleavage enzyme (SCC) within the CZ regions also decreased. Lipid granules increased in the SCZ but decreased in the CZ region, and alkaline and acid phosphatases levels increased significantly. Dark and broad cristae and numbers of mitochondria (mt) decreased within the adreno-cortical regions. But lipid droplets and rough endoplasmic reticulum (rER) increased. Large numbers of dark and dead mitochondria and less number of free ribosomes were also found within the pinealocytes cytoplasm. Whereas, in TP-SP treatment groups during breeding phase, weight of adrenal and pineal glands decreased. Alkaline and acid phophatases levels also decreased. But, cholesterol and ascorbic acid level and intensity of lipids droplets increased within the SCZ region. On the other hand, owing to TP-LP treatment during regressive phase-I, weight of adrenal gland, adreno-cortical cord widths, and nuclear diameter of SCZ and CZ regions increased significantly. High intensities of SCC enzymes were found in both the SCZ and CZ regions as well. Lipid droplets and rER decreased but mitochondria increased in the adreno-cortical region. Cholesterol and ascorbic acid level and intensity of lipids droplets in both the SCZ and CZ regions decreased. But alkaline and acid phophatases levels increased. And weight of pineal gland and its nuclear diameter decreased. Here, free ribosomes and the number of mitochondria decreased. In the TP-SP treatment groups, there is no major change within the adrenal gland, adrenocortical regions, and SCC enzymes. Intensity of lipids droplets increased within the CZ region. The nuclear diameters of pinealocytes were smaller than control. Cholesterol and ascorbic acid levels also decreased and alkaline and acid phophatases levels increased when compared to that in control. The number of mitochondria, smooth endoplasmic reticulum (sER), and Golgi complex was the same as in control groups in both the adrenal and pineal glands. But mitochondria and rER increased in both the adrenal and pineal gland cytoplasm. The present studies on the male domestic pigeons clearly indicate that the activities of the adrenal and pineal glands during the regressive phases-I showed a clear relationship with the breeding birds. However, TP treatment in the birds during breeding phases showed some depressive results due to melatonin rhythm like the non-breeding or regressive phase of adult birds. [ABSTRACT FROM AUTHOR]

The molecular circadian clock mechanism is highly conserved between mammalian and avian species. Avian circadian timing is regulated at multiple oscillatory sites, including the retina, pineal, and hypothalamic suprachiasmatic nucleus (SCN). Based on the authors' previous studies on the rat ovary, it was hypothesized that ovarian clock timing is regulated by the luteinizing hormone (LH) surge. The authors used the chicken as a model to test this hypothesis, because the timing of the endogenous LH surge is accurately predicted from the time of oviposition. Therefore, tissues can be removed before and after the LH surge, allowing one to determine the effect of LH on specific clock genes. The authors first examined the 24-h expression patterns of the avian circadian clock genes of Bmal1, Cry1, and Per2 in primary oscillatory tissues (hypothalamus and pineal) as well as peripheral tissues (liver and ovary). Second, the authors determined changes in clock gene expression after the endogenous LH surge. Clock genes were rhythmically expressed in each tissue, but LH influenced expression of these clock genes only in the ovary. The data suggest that expression of ovarian circadian clock genes may be influenced by the LH surge in vivo and directly by LH in cultured granulosa cells. LH induced rhythmic expression of Per1 and Bmal1 in arrhythmic, cultured granulosa cells. Furthermore, LH altered the phase and amplitude of clock gene rhythms in serum-shocked granulosa cells. Thus, the LH surge may be a mechanistic link for communicating circadian timing information from the central pacemaker to the ovary. (Author correspondence: stischkau@siumed.edu) [ABSTRACT FROM AUTHOR]

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 (g Aanat-2) and HIOMT-2 (g Hiomt-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 g Aanat-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 g Aanat-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 g Aanat-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 liver of the goldfish. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

The importance of light in the temporal organization of photoreceptor proteins and melatonin-producing system has been investigated for the first time in the pineal of a tropical fish. In this study, an identical experimental paradigm was followed during the four distinct phases of an annual cycle in adult carps ( Catla catla) maintained either under natural photoperiod (NP) or continuous illumination (LL) or darkness (DD) for 30 days. At the end of each experiment, the pineal from fish in each experimental group was collected either at 06:00, 12:00, 18:00, or 24:00 in a daily cycle and assessed by Western blot analysis for pineal rod-like opsin, α-transducin, and AANAT. The same animals were also used for measurement of serum melatonin levels, and the serum as well as intra-pineal Ca++ levels at each timepoint. The study revealed a daily rhythmicity with a peak at 12:00 h and nadir at 24:00 h in the band intensity of pineal rod-like opsin and α-transducin in NP fish, while the band intensities of these photo-pigment proteins remained high under LL and low under DD, irrespective of clock hour during the 24 h cycle. The band intensity of pineal AANAT, levels of serum melatonin, and both serum Ca++ and intra-pineal Ca++ were maximum at 24:00 h and minimum at 12:00h in NP fish, and they were significantly lower under LL and higher under DD at each point of study. The results showed loss of daily rhythm in each studied variable in both LL and DD carps, suggesting that their circadian organization is dependent on the external light-dark conditions, rather than an endogenous circadian oscillator in the pineal. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

This study investigates the relative strengths of food and light zeitgebers in synchronization of circadian rhythms of Indian weaver birds and the role of the pineal gland in food-induced synchronization of the circadian activity rhythms. Two experiments were performed. In the first experiment, six birds were concurrently exposed for 10 days to PA 12/12 (12 h food present: 12 h food absent) and LD 12/12 (12 h light: 12 h dark). Then, the PA 12/12 cycle was reversed: food was present during the dark period of the LD 12/12 cycle. After 15 days, birds were released into constant dim light (LLdim). During exposure to overlapping light and food availability periods, birds were active only during the daytime. When light and food availability periods were presented in antiphase, two of six birds became night active. However, with the removal of the light zeitgeber (i.e., under LLdim), all birds were synchronized with reversed PA 12/12; hence, they were active during the subjective night (i.e., the period corresponding to darkness [ZT12-0] of the preceding LD 12/12). The second experiment examined whether the pineal contributed to the food-induced synchronization. After two weeks of concurrent PA 12/12 and LD 12/12 exposure, six birds were released into LLdim for 2.5 weeks. Under LLdim, five of six birds were synchronized to PA 12/12 with the circadian period (tau, τ) = 24 h. The LD 12/12 was restored, and after seven days, birds were pinealectomized (pinx). After 2.5 weeks, pinx birds were again released into LLdim for 2.5 weeks. Under LLdim, pinx birds did not become arrhythmic; instead, they appeared synchronized to PA 12/12 with τ = 24 h (n = 4) or ∼24 h (n = 2). We conclude that both food and light act as zeitgebers, although light appears to be the relatively stronger cue when the two are present together, as in the natural environment. We also found that the pineal is not necessary for food-induced synchronization. The findings suggest that food cycles could act as the synchronizer of circadian rhythmicity in biological functions in individuals held in an aperiodic environment. [ABSTRACT FROM AUTHOR]

Arylalkylamine N-acetyltransferase (AA-NAT) is the rhythm-generating enzyme for the synthesis of pineal melatonin. Molecular investigations have revealed two biological models for the activation of AA-NAT. In rodent species, Aa-nat gene transcription is turned off during the daytime and markedly activated at night. In primates, sheep, and cows, the Aa-nat gene is constitutively transcripted with no visible daily variations. This inter-species difference in Aa-nat gene regulation leads to different daily profiles in melatonin synthesis and release. Thus, the nighttime onset of the rise in circulating melatonin is delayed and slow in rodents, whereas it is fast and sharp in sheep. In the camel (Camelus dromedarius), we have observed that circulating melatonin rises immediately after sunset, suggesting AA-NAT activity is regulated at the post-transcriptional level. In agreement with this hypothesis, we report herein the amount of Aa-nat mRNA in the camel pineal gland is high, during both the day and night with no daily variations, while melatonin concentration in the same pineal tissue is five times higher during the night than daytime. (Author correspondence: simonneaux@neurochem.u-strasbg.fr) [ABSTRACT FROM AUTHOR]

The purpose of this work was to investigate the circadian melatonin system in two tropical teleost species characterized by different behavioral habits, Nile tilapia (diurnal) and African catfish (nocturnal). To do so, fish were subjected to either a control photoperiod (12L:12D), continuous light (LL) or darkness (DD), or a 6L:6D photoperiod. Under 12L:12D, plasma melatonin levels were typically low during the photophase and high during the scotophase in both species. Interestingly, in both species, melatonin levels significantly decreased prior to the onset of light, which in catfish reached similar basal levels to those during the day, demonstrating that melatonin production can anticipate photic changes probably through circadian clocks. Further evidence for the existence of such pacemaker activity was obtained when fish were exposed to DD, as a strong circadian melatonin rhythm was maintained. Such an endogenous rhythm was sustained for at least 18 days in Nile tilapia. A similar rhythm was shown in catfish, although DD was only tested for four days. Under LL, the results confirmed the inhibitory effect of light on melatonin synthesis already reported in other species. Finally, when acclimatized to a short photo-cycle (6L:6D), no endogenous melatonin rhythm was observed in tilapia under DD, with melatonin levels remaining high. This could suggest that the circadian clocks cannot entrain to such a short photocycle. Additional research is clearly needed to further characterize the circadian axis in teleost species, identify and localize the circadian clocks, and better understand the environmental entrainment of fish physiology. [ABSTRACT FROM AUTHOR]

The aim of the current investigation was to study the effect of lithium on circadian rhythms of pineal – testicular hormones by quantitations of pineal and serum serotonin, N-acetylserotonin and melatonin, and serum testosterone at four time points (06.00, 12.00, 18.00 and 24.00) of a 24-hr period under normal photoperiod (L:D), reversed photoperiod (D:L), constant light (L:L) and constant dark phase (D:D) in rats. Circadian rhythms were observed in pineal hormones in all the combinations of photoperiodic regimens, except in constant light, and in testosterone levels in all the photoperiodic combinations. Pineal and serum N-acetylserotonin and melatonin levels were higher than serotonin at night (24.00 hr), in natural L:D cycle, in reversed L:D cycle or similar to normal L:D cycle in constant dark phase, without any change in constant light. In contrast, testosterone level was higher in light phase (12.00 hr through 18.00 hr) than in the dark phase (24.00 hr through 06.00 hr) in normal L:D cycle, in reversed L:D cycle, similar to normal L:D cycle in constant dark (D:D), and reversed to that of the normal L:D cycle in constant light (L:L). Lithium treatment (2 mEq/kg body weight daily for 15 days) suppressed the magnitude of circadian rhythms of pineal and serum serotonin, N-acetylserotonin and melatonin, and testosterone levels by decreasing their levels at four time points of a 24-hr period in natural L:D or reversed D:L cycle and in constant dark (D:D). Pineal indoleamine levels were reduced after lithium treatment even in constant light (L:L). Moreover, lithium abolished the melatonin rhythms in rats exposed to normal (L:D) and reversed L:D (D:L) cycles, and sustained the rhythms in constant dark. But testosterone rhythm was abolished after lithium treatment in normal (L:D)/reversed L:D (D:L) cycle or even in constant light/dark. The findings indicate that the circadian rhythm exists in pineal hormones in alternate light – dark cycle (L:D/D:L) and in constant dark (D:D), but was absent in constant light phase (L:L) in rats. Lithium not only suppresses the circadian rhythms of pineal hormones, but abolishes the pineal melatonin rhythm only in alternate light – dark cycles, but sustains it in constant dark. The testosterone rhythm is abolished after lithium treatment in alternate light – dark cycle and constant light/dark. It is suggested that (a) normal circadian rhythms of pineal hormones are regulated by pulse dark phase in normal rats, (b) lithium abolishes pineal hormonal rhythm only in pulse light but sustains it in constant dark phase, and (c) circadian testosterone rhythm occurs in both pulse light or pulse dark phase in normal rats, and lithium abolishes the rhythm in all the combinations of the photoperiod. The differential responses of circadian rhythms of pineal and testicular hormones to pulse light or pulse dark in normal and lithium recipients are discussed. [ABSTRACT FROM AUTHOR]

Objective : Pineal function has been considered particularly as a neuroendocrine modulator in hormone responsive tumors, like the hormone-dependent mammary tumors. The complexity of the gland function, moreover, is denoted by the presence of a local renin-angiotensin-system (RAS) that regulates melatonin biosynthesis. Classically, angiotensin II (Ang II) has been considered as the effector peptide of the RAS, but Ang II is not the only active peptide. Several of its degradation products, including angiotensin III (Ang III) and angiotensin IV (Ang IV) also possess biological functions. These peptides are formed via the activity of several aminopeptidases. Our aim is to know their role in the regulation of pineal RAS and breast cancer. Design : Aminopeptidase N (APN), aminopeptidase B (APB) and aminopeptidase A (aspartyl- and glutamyl-aminopeptidase, APA) activities are measured in the pineal gland of rats with breast cancer induced by N-methyl nitrosourea (NMU). Methods : Aminopeptidase activities were measured fluorimetrically using their corresponding aminoacyl-ß-naphthylamides as substrates. Results : Specific APN and APB activities in pineal gland of controls and NMU-treated rats were not modified. Aspartyl aminopeptidase activity significantly decreased in NMU-treated rats when compared with control group. On the contrary, glutamyl aminopeptidase activity did not show significant differences between groups. Conclusions : We propose that the local RAS in pineal gland is modified in rats with breast cancer induced by NMU through the inhibition of AspAP activity, which may lead to increased levels of Ang II. Ang II could be responsible of the overproduction of melatonin, supporting a mechanism to restrain the promotion and/or progression of breast cancer. [ABSTRACT FROM AUTHOR]

The perivascular space of the rat pineal gland is known to contain phagocytic cells that are immunoreactive for leukocyte antigens, and thus they appear to belong to the macrophage/microglial cell line. These cells also contain MHC class II proteins. We investigated this cell type in the pineal gland of mice. Actively phagocytosing cells with a prominent lysosomal system were found in the pericapillary spaces of the mouse pineal gland following intravenous injection of horseradish peroxidase. The cells also exhibited strong acid phosphatase activity. Perivascular cells were immunopositive for MHC class II protein and for CD68, a marker of monocytes/phagocytes. This study verifies that perivascular phagocytes with antigen‐presenting properties are present in the mouse pineal gland. [ABSTRACT FROM AUTHOR]

The defining feature of the pineal gland is the capacity to function as a melatonin factory that operates on a ∼⃒24 h schedule, reflecting the unique synthetic capacities of the pinealocyte. Melatonin synthesis is typically elevated at night and serves to provide the organism with a signal of nighttime. Melatonin levels can be viewed as hands of the clock. Issues relating to the evolutionary events leading up to the immergence of this system have not received significant attention. When did melatonin synthesis appear in the evolutionary line leading to vertebrates? When did a distinct pineal gland first appear? What were the forces driving this evolutionary trend? As more knowledge has grown about the pinealocyte and the relationship it has to retinal photoreceptors, it has become possible to generate a plausible hypothesis to explain how the pineal gland and the melatonin rhythm evolved. At the heart of the hypothesis is the melatonin rhythm enzyme arylalkylamine N‐acetyltransferase (AANAT). The advances supporting the hypothesis will be reviewed here and expanded beyond the original foundation; the hypothesis and its implications will be addressed. [ABSTRACT FROM AUTHOR]

In the rat pineal gland, the steady‐state level of arylalkylamine N ‐acetyltransferase (AANAT) protein is controlled by transcriptional and translational mechanisms as well as by proteasome‐mediated degradation. Studies with proteasome inhibitors, MG132 and clasto‐lactacystin β‐lactone (c‐lact), show two opposite effects of proteasomal inhibition on norepinephrine (NE)‐induction of Aanat . Addition of MG132 or c‐lact following NE stimulation causes an increase in AANAT protein level and enzyme activity without affecting the level of Aanat mRNA. In contrast, addition of inhibitors prior to NE stimulation reduces the NE‐stimulated Aanat mRNA, AANAT protein, and enzyme activity. The inhibitory effect of proteasomal inhibition on adrenergic‐induced Aanat transcription appears specific for Aanat because it has no effect on the adrenergic induction of mitogen‐activated protein kinase phosphatase‐1 ( mkp‐1 ). The effects of the proteasome inhibitors on NE‐stimulated Aanat induction appear to be mediated by accumulation of a protein repressor. [ABSTRACT FROM AUTHOR]

Circadian rhythms of amphibians and reptiles in the field and under semi-natural conditions and the underlying mechanisms, including the ways of entrainment to environmental cues and the oscillators driving the rhythms, have been reviewed. Studies on the behavioral rhythms in the field are meager in both amphibians and reptiles. In anuran amphibians, Xenopus adults showed more robust nocturnal locomotor activity than did tadpoles. This indicates the ecological significance of the differences in activity pattern shown by amphibians at different life stages, because differences between adults and young in the same environment may serve to isolate partially the young from the adults' cannibalism. In reptiles, free-running rhythms are more robust and continue for a longer time compared to amphibians. In both amphibians and reptiles, multi-photoreceptors are involved in photo-entrainment of circadian rhythms. The eyes, pineal complex and deep brain comprise a multi-oscillator system as well as a multi-photoreceptor system. [ABSTRACT FROM AUTHOR]

A clock is conceptualized as comprising an input-pacemaker-output system. An overtly measured output, such as the rhythm of activity, feeding or secretion of melatonin, is the consequence of underlying activity of genes at all three levels (input, pacemaker and output) of the clock system. Molecular biochemical studies suggest that the rhythmicity is generated intrinsically within specialized tissues (pacemaker cells) by autoregulatory feedback loops involving gene transcription and post-translational modifications of the 'clock proteins'. Each tissue that can generate oscillations and produce a stable rhythmic output in synchronization with external (environmental) signals is called a clock, and birds appear to have multiple clocks. Independent input-pacemaker-output systems are present at a minimum of three levels -- the retina of the eyes, the pineal gland, and the hypothalamus. This is different from mammals in which input, pacemaker and output are localized in different structures. Further, in birds, each clock interacts with one or more other clocks, and, together, these clocks form a centralized clocking system (CCS). The degree of interdependence between the components of the CCS can vary greatly between species as well as between seasons within an individual. All these properties make the avian CCS a highly complex and diverse timing system. In this article, we will first summarize evidence for the possession of clocks at the three levels (the retina of the eye, the pineal gland, and the hypothalamus), and then present examples that show the complexity and diversity of the avian CCS. We will also analyze how the avian CCS is integrated to produce stable and yet highly adaptive short- and long-term periodic functions. [ABSTRACT FROM AUTHOR]

The pineal complex of reptiles is a morphologically and functionally connected set of organs that originates as an evagination of the roof of the diencephalon. It is formed by two structures: the pineal organ and the parietal eye. The pineal gland is present in Chelonia, Squamata and Rhynchocephalia, but not in Crocodilia. The parietal eye is present in some species of lizards (Squamata) and in the tuatara (Rhynchocephalia). Both the pineal gland and the parietal eye are photosensitive. In particular, the parietal eye is an highly organized photoreceptive structure, with a well-defined lens, cornea and retina. The most important (and studied) secretory product of this complex is the hormone melatonin which is synthesized by both organs (pineal and parietal eye). The pineal organ is believed to be the neuroendocrine transducer of changes in photoperiod and environmental temperature and it has been demonstrated to have a functional role in many aspects of reptilian biology. Melatonin has an influence on the mechanisms controlling thermoregulation (behavioral and physiological), because its manipulation or removal may produce significant alterations of behavioral and physiological thermoregulatory parameters. The reptilian pineal complex may also possess self-sustained circadian oscillators which are involved in the circadian organization of these animals and in their reproduction. It is believed that many of the roles played by the pineal complex are mediated by the hormone melatonin, since exogenous administration of melatonin may affect the animal's physiology and/or behavior. The present paper will review the current knowledge about the neuroendocrinology and functional roles of the reptilian pineal complex. [ABSTRACT FROM PUBLISHER]