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Besides life extension in mice and fruit flies, Epithalon effects include the postponing vision loss in Campbell rats with hereditary pigmental dystrophy. A uniting aspect of such a range of activities might be the participation of transcription factors, since they are often highly conservative in evolution and, on the other hand, may be strictly tissue-specific. The targets of Epithalon may include transfactors that in mammals are specific for the pineal gland and retina and exhibit impaired functions in the aged pineal gland. Circadian Regulation of Pineal Gland Rhythmicity. PubMed Central.

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.

The review analyzed morphology, molecular and functional aspects of pineal gland aging and methods of it correction.

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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.


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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. The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light.

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In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression.


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  5. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model. Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas.

    The purpose of this research was to study age-related changes in functioning of pineal and pancreatic glands of non-human primates, rhesus monkeys, and to elucidate the possibility of their corrections with the help of epitalon, a synthetic analogue of the pharmacopoeia drug epithalamin. In old years animals, the basal plasma levels of glucose and insulin were found to be higher, while the night melatonin level was lower in comparison with years young animals.

    After the glucose administration to old monkeys, a larger area under the curve of the plasma glucose response, a reduced glucose 'disappearance' rate, and a reduced insulin peak 5 min after the glucose administration were observed in comparison with young animals in similar experiments. The epitalon administration to old monkeys caused the decrease in the basal levels of glucose and insulin and the increase in the basal night melatonin level. Additionally, in the case of old monkeys, epitalon decreased the area under the plasma glucose response curve, markedly increased the glucose 'disappearance' rate and normalized the plasma insulin dynamics in response to glucose administration.

    Yet, it has not affected the hormonal and metabolic changes in young animals. Thus, epitalon is a promising factor for restoring the age-related endocrine dysfunctions of primates. Among the rhythms under SCN Lymphopoiesis in the chicken pineal gland. 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 da pineal glands of both breeds. Descartes and the pineal gland in animals: a frequent misinterpretation.

    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.

    A modulatory role of the Rax homeobox gene in mature pineal gland function : Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse. The retinal and anterior neural fold homeobox gene Rax controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland , a forebrain structure devoted to melatonin synthesis.

    The role of Rax in pineal function is unknown. In order to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal -specific Rax conditional knockout mouse.

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    Deletion of Rax in the pineal gland did not affect morphology of the gland , suggesting that Rax is not essential for pineal gland development. In contrast, deletion of Rax in the eye generated an anophthalmic phenotype. In addition to the loss of central visual pathways, the suprachiasmatic nucleus of the hypothalamus housing the circadian clock was absent, indicating that the retinohypothalamic tract is required for the nucleus to develop.

    Telemetric analyses confirmed the lack of a functional circadian clock. Arylalkylamine N-acetyltransferase Aanat transcripts, encoding the melatonin rhythm-generating enzyme, were undetectable in the pineal gland of the Rax conditional knockout under normal conditions, whereas the paired box 6 homeobox gene, known to regulate pineal development, was up-regulated. By injecting isoproterenol, which mimics a nocturnal situation in the pineal gland , we were able to induce pineal expression of Aanat in the Rax conditional knockout mouse, but Aanat transcript levels were significantly lower than those of Rax-proficient mice.

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    Our data suggest that Rax controls pineal gene expression and via Aanat may modulate melatonin synthesis. 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.

    In addition to miR, miR and miR are also highly enriched in the pineal gland , a distinctive pattern also found in the retina. During development, the abundance of most pineal gland -enriched miRNAs increases; however, there is a marked decrease in at least one, miR Additionally, a miR targeted antagonist increased melatonin synthesis in neonatal pinealocytes. These observations support the hypothesis that miR suppresses Aanat mRNA levels during development and that the developmental decrease in miR abundance promotes melatonin synthesis.

    The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body.

    Pineal calcification jeopardizes melatonin's synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation.

    The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.

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    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. The pineal gland CP is located centrally in the brain and produces melatonin. Cysts and concrements are frequent findings on MRI but their significance is still unclear. The visualization of CP is difficult due to its location and surrounding structures and so far, no standardized method exists.

    New studies suggest a correlation between CP-morphology and melatonin secretion as well as a connection between melatonin, disturbed circadian rhythm, and the development of cancer and cardiovascular diseases, underlining the need for a standardized approach to CP on MRI.

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    GABAergic signaling in the rat pineal gland. 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. The cells represent a subset of interstitial cells while the nerve fibers were distinct from the sympathetic innervation. 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.

    GABA repolarized the membrane and shut off such calcium rises. In 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.

    Yu, Haijie; Benitez, Sergio G. In 48—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. Neuropeptide Y in the adult and fetal human pineal gland.

    Neuropeptide Y was isolated from the porcine brain in and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle.

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