Showing papers on "Pinealocyte published in 2020"

Is Melatonin the Cornucopia of the 21st Century

Abstract: Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes and extra-pineal cells, plays an important role in timing circadian rhythms (24-h internal clock) and regulating the sleep/wake cycle in humans. However, in recent years melatonin has gained much attention mainly because of its demonstrated powerful lipophilic antioxidant and free radical scavenging action. Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant. Melatonin-induced signal transduction through melatonin receptors promotes the expression of antioxidant enzymes as well as inflammation-related genes. Melatonin also exerts an immunomodulatory action through the stimulation of high-affinity receptors expressed in immunocompetent cells. Here, we reviewed the efficacy, safety and side effects of melatonin supplementation in treating oxidative stress- and/or inflammation-related disorders, such as obesity, cardiovascular diseases, immune disorders, infectious diseases, cancer, neurodegenerative diseases, as well as osteoporosis and infertility.

The Lhx4 homeobox transcript in the rat pineal gland: Adrenergic regulation and impact on transcripts encoding melatonin-synthesizing enzymes

Abstract: Homeobox genes generally encode transcription factors involved in regulating developmental processes. In the pineal gland, a brain structure devoted to nocturnal melatonin synthesis, a number of homeobox genes are also expressed postnatally; among these is the LIM homeobox 4 gene (Lhx4). We here report that Lhx4 is specifically expressed in the postnatal pineal gland of rats and humans. Circadian analyses revealed a fourfold rhythm in Lhx4 expression in the rat pineal gland, with rhythmic expression detectable from postnatal day 10. Pineal Lhx4 expression was confirmed to be positively driven by adrenergic signaling, as evidenced by in vivo modulation of Lhx4 expression by pharmacological (isoprenaline injection) and surgical (superior cervical ganglionectomy) interventions. In cultured pinealocytes, Lhx4 expression was upregulated by cyclic AMP, a second messenger of norepinephrine. By use of RNAscope technology, Lhx4 transcripts were found to be exclusively localized in melatonin-synthesizing pinealocytes. This prompted us to investigate the possible role of Lhx4 in regulation of melatonin-producing enzymes. By use of siRNA technology, we knocked down Lhx4 by 95% in cultured pinealocytes; this caused a reduction in transcripts encoding the melatonin-producing enzyme arylalkylamine N-acetyl transferase (Aanat). Screening the transcriptome of siRNA-treated pinealocytes by RNAseq revealed a significant impact of Lhx4 on the phototransduction pathway and on transcripts involved in development of the nervous system and photoreceptors. These data suggest that rhythmic expression of Lhx4 in the pineal gland is controlled via an adrenergic-cyclic AMP mechanism and that Lhx4 acts to promote nocturnal melatonin synthesis.

Action de la photopériode sur la reproduction des équidés

Abstract: Mares and stallions have their reproductive period during the season where the days are long. This annual reproductive rhythm is controlled by the length of the daylight. Treatment of mares during winter when their ovaries are normally inactive, with an artificial light during 14.5 h per day, beginning around the winter solstice, causes the first ovulation of the year to occur at an earlier date. Studies have verified certain stages in the process by which equine species perceive light. The light message is transformed into nerve impulse by specialized retinal cells. These impulses are transmitted through the supra-chiasmatic nucleus and the cervical superior nucleus to the pineal gland. The pinealocytes respond to noradrenergic stimulation by secreting melatonin. The administration of exogenous melatonin by subcutaneous implants or by oral route suppresses the photostimulation effect. The studies on the use of melatonin implants in mares to obtain reproductive activity out of the breeding season are now in progress. The GnRH secretion is regulated by such neuromediators as dopamine, noradrenalin, serotonin and opioids. Naloxone, an opioid antagonist, induces a GnRH secretion that is followed by LH and FSH release, in mares during the winter period of inactivity. The thyroid hormones also seem to act on the annual rhythm of GnRH secretion. An alternation of one month of short days and one month of long days which suppresses the seasonal cycle of variation in small ruminant males has not yet been shown to have a similar effect on mares or on stallions.

Fluoride-Free Diet Stimulates Pineal Growth in Aged Male Rats.

Abstract: The pineal gland is a naturally calcifying endocrine organ which secretes the sleep-promoting hormone melatonin. Age-related changes of the pineal have been observed, including decreased pinealocyte numbers, increased calcification, and a reduction in melatonin production. Since fluoride is attracted to calcium within the pineal gland, this study sought to examine the effects of a fluoride-free diet on the morphology of the pineal gland of aged male rats (26 months old). All animals had previously been raised on standard fluoridated food and drinking water. These control animals were compared to other animals that were placed on a fluoride-free diet ("fluoride flush") for 4 or 8 weeks. At 4 weeks, pineal glands from fluoride-free animals showed a 96% increase in supporting cell numbers and at 8 weeks a 73% increase in the number of pinealocytes compared to control animals. In contrast, the number of pinealocytes and supporting cells in animals given an initial 4-week fluoride flush followed by a return to fluoridated drinking water (1.2 ppm NaF) for 4 weeks were not different from control animals. Our findings therefore demonstrate that a fluoride-free diet encouraged pinealocyte proliferation and pineal gland growth in aged animals and fluoride treatment inhibited gland growth. These findings suggest that dietary fluoride may be detrimental to the pineal gland.

Arecoline inhibits pineal-testis function in experimentally induced hypothyroid rats.

Abstract: 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.

Circadian regulation and molecular role of the Bsx homeobox gene in the adult pineal gland.

Abstract: The pineal gland is a neuroendocrine organ responsible for production of the nocturnal hormone melatonin. A specific set of homeobox gene-encoded transcription factors govern pineal development, and some are expressed in adulthood. The brain-specific homeobox gene (Bsx) falls into both categories. We here examined regulation and function of Bsx in the mature pineal gland of the rat. We report that Bsx is expressed from prenatal stages into adulthood, where Bsx transcripts are localized in the melatonin-synthesizing pinealocytes, as revealed by RNAscope in situ hybridization. Bsx transcripts were also detected in the adult human pineal gland. In the rat pineal gland, Bsx was found to exhibit a 10-fold circadian rhythm with a peak at night. By combining in vivo adrenergic stimulation and surgical denervation of the gland in the rat with in vitro stimulation and transcriptional inhibition in cultured pinealocytes, we show that rhythmic expression of Bsx is controlled at the transcriptional level by the sympathetic neural input to the gland acting via adrenergic stimulation with cyclic AMP as a second messenger. siRNA-mediated knockdown (>80% reduction) in pinealocyte cultures revealed Bsx to be a negative regulator of other pineal homeobox genes, including paired box 4 (Pax4), but no effect on genes encoding melatonin-synthesizing enzymes was detected. RNA sequencing analysis performed on siRNA-treated pinealocytes further revealed that downstream target genes of Bsx are mainly involved in developmental processes. Thus, rhythmic Bsx expression seems to govern other developmental regulators in the mature pineal gland.

Advances in Characterizing Recently-Identified Molecular Actions of Melatonin: Clinical Implications

Abstract: Melatonin, N-acetyl-5-methoxy-tryptamine, was discovered to be a product of serotonin metabolism in the mammalian pineal gland where its synthesis is under control of the light:dark cycle. Besides its regulatory pathway involving ganglion cells in the retina, the neural connections between the eyes and the pineal gland include the master circadian clock, the suprachiasmatic nuclei, and the central and peripheral nervous systems. Since pineal melatonin is released into the blood and into the cerebrospinal fluid, it has access to every cell in an organism and it mediates system-wide effects. Subsequently, melatonin was found in several extrapineal organs and, more recently, perhaps in every cell of every organ. In contrast to the pinealocytes, non-pineal cells do not discharge melatonin into the blood; rather it is used locally in an intracrine, autocrine, or paracrine manner. Melatonin levels in non-pineal cells do not exhibit a circadian rhythm and do not depend on circulating melatonin concentrations although when animals are treated with exogenous melatonin it is taken up by presumably all cells. Mitochondria are the presumed site of melatonin synthesis in all cells; the enzymatic machinery for melatonin synthesis has been identified in mitochondria. The association of melatonin with mitochondria, because of its ability to inhibit oxidative stress, is very fortuitous since these organelles are a major site of damaging reactive oxygen species generation. In this review, some of the actions of non-pineal-derived melatonin are discussed in terms of cellular and subcellular physiology.

Pharmacological Correction of Alterations in Apoptosis of Neurons of the Hypothalamic Suprachiasmatic Nucleus and Pinealocytes in Rats during Aging and under Stress

Abstract: The pineal gland is known to play an important role in adaptogenesis. The hypothalamus is one of the main links of the stress-reactive system; it participates in the regulation of the involution of the whole body. Thus, the study of changes in these organs under stress and during aging is of considerable interest. The goal of this work is to study the apoptosis mechanisms of pinealocytes and neurosecretory cells of the hypothalamic suprachiasmatic nucleus in aging, under stress, and during pharmacological correction of involutional processes and stress response (antioxidant α-tocopherol acetate, immunomodulator Cycloferon). Young (10–12 months) and old (24–30 months) Wistar rats were used as the model organism. Age-related features of the dynamics of apoptosis of pinealocytes and neurosecretory cells of the hypothalamic suprachiasmatic nucleus were studied via TUNEL and immunohistochemistry, and the potential for the pharmacological correction of apoptotic processes were determined. An age-dependent increase in the level of apoptosis of cells of the suprachiasmatic nucleus and pineal gland in rats was revealed. Stress (immobilization) led to increased cell death, which was more significant in older animals. This indicates that the pineal gland and suprachiasmatic nucleus, traditionally regarded as regulators of circadian rhythms, are also actively involved in general adaptation processes. The studied drugs (α-tocopherol-acetate, Cycloferon, and their combination) have a pronounced antiapoptotic, cytoprotective effect under physiological conditions during aging and under nonspecific emotional stress (immobilization) in young and old animals. The regulatory effect is implemented via activation of the expression of the antiapoptotic protein Bcl-2 in neurosecretory cells of the suprachiasmatic nucleus and pinealocytes.

Morpho-functional state of rats pineal gland and suprachismatic nucleus of hypothalamus after different regimes of exogenous melatonin administration

Abstract: In modern society increase of digitalization associated with grown exceed level of light at night – a new type of pollution. Presence of light at night inhibited endogenous melatonin synthesis by pineal gland, that influence on circadian system work cycles, so organism oftenbroken regime of wake/sleep, meals, physical activity. Also, a lack of melatonin in some certain time of dayand low melatonin concentration both, were shown take some intervention in diseases development through incorrect regulation of clock-depended genes expression. In connect with this, some latest clinical protocol in therapy or clinical trials of many different pathologies (for example, insomnia, metabolic syndrome, cardiovascular diseases, central nervous and immune system trouble, cancer, viral infection, etc.) include exogenous melatonin usage. As melatonin perform his function via endocrine and paracrine ways in variety types of cell, his application take place in wide range of doses and in different time of day (chronotherapeutic approach). Therefore, important to control state of circadian system central elements – pineal gland (main producer of endogenous melatonin) and suprachiasmatic nucleus (SCN) of hypothalamus (central pacemaker of circadian rhythm) in conditionsof exogenous melatonin treatment. Thus, the main goal of our research were analysis of rats pineal gland and hypothalamic SCN morpho-functional state after different time (morning, evening and continuously with drinking water) melatonin daily administration. Melatonin was administered by gavage for 7 weeks in dose 30 mg/kg 1 h before lights-off (M ZT11, evening), or 1 h after lights-on (M ZT01, morning), or continuously with drinking water during day-night period (MW). After melatonin use only in MW group pineal gland demonstrates changes in morphology (pinealocytes nucleus had mild basophilic color) and morphometric (increased cross-sectional area of the pinealocytes nucleus in compare with control group) analysis data. Besides, some similar changes were observed in SCN: the cross-sectional area of the SCN neurons nucleus grown in case of usage each of regime melatonin administration, while morphology characteristic remains without any alteration. In general, it suggesting about having by melatonin non-inhibiting features in context of circadian system feedback loop and supposing wide potential for melatonin use with absent huge side effect on central elements of above mentioned system.

The Pineal and Reproduction in Birds

Abstract: Comprehensive reviews dealing with the embryology, morphology, vascularization, innervation, and cytology of avian pineal glands are available. Among species of birds, the morphology and cytology of the pineal gland are remarkably varied. According to Collin, the unique cell type in the avian pineal, the secretory pinealocyte, is evolutionarily derived from a cone-like receptor cell found among some reptiles and anamniotes. The rhythmic variation in melatonin content of the pineal gland of chickens persists as a free-running, circadian rhythm for at least 2 weeks in continuous darkness, but it disappears within 2 weeks in constant light. The autotransplanted pineal gland of chickens apparently released greater amounts of melatonin into the blood at night than during the day, since by bioassay melatonin could be detected there only when sampled at night. The injury occasioned by the surgical removal of the pineal gland can affect the measured response in various ways, including increasing the opacity of the skull and underlying tissues.