Showing papers on "Pinealocyte published in 2018"

Immune-pineal axis - acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes.

Abstract: Melatonin is well known for its circadian production by the pineal gland, and there is a growing body of data showing that it is also produced by many other cells and organs, including immune cells. The chronobiotic role of pineal melatonin, as well as its protective effects in vitro and in vivo, have been extensively explored. However, the interaction between the chronobiotic and defence functions of endogenous melatonin has been little investigated. This review details the current knowledge regarding the coordinated shift in melatonin synthesis from the pineal gland (circadian and monitoring roles) to the regulation of acute immune responses via immune cell production and autocrine effects, producing systemic interactions termed the immune-pineal axis. An acute inflammatory response drives the transcription factor, NFκB, to switch melatonin synthesis from pinealocytes to macrophages/microglia and, upon acute inflammatory resolution, back to pinealocytes. The potential pathophysiological relevance of immune-pineal axis dysregulation is highlighted, with both research and clinical implications, across several medical conditions, including host/parasite interaction, neurodegenerative diseases and cancer. LINKED ARTICLES: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc.

Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypes and cell type-specific daily patterns of gene expression.

Abstract: The vertebrate pineal gland is dedicated to the production of the hormone melatonin, which increases at night to influence circadian and seasonal rhythms. This increase is associated with dramatic changes in the pineal transcriptome. Here, single-cell analysis of the rat pineal transcriptome was approached by sequencing mRNA from ~17,000 individual pineal cells, with the goals of profiling the cells that comprise the pineal gland and examining the proposal that there are two distinct populations of pinealocytes differentiated by the expression of Asmt, which encodes the enzyme that converts N-acetylserotonin to melatonin. In addition, this analysis provides evidence of cell-specific time-of-day dependent changes in gene expression. Nine transcriptomically distinct cell types were identified: ~90% were classified as melatonin-producing α- and β-pinealocytes (1:19 ratio). Non-pinealocytes included three astrocyte subtypes, two microglia subtypes, vascular and leptomeningeal cells, and endothelial cells. α-Pinealocytes were distinguished from β-pinealocytes by ~3-fold higher levels of Asmt transcripts. In addition, α-pinealocytes have transcriptomic differences that likely enhance melatonin formation by increasing the availability of the Asmt cofactor S-adenosylmethionine, resulting from increased production of a precursor of S-adenosylmethionine, ATP. These transcriptomic differences include ~2-fold higher levels of the ATP-generating oxidative phosphorylation transcriptome and ~8-fold lower levels of the ribosome transcriptome, which is expected to reduce the consumption of ATP by protein synthesis. These findings suggest that α-pinealocytes have a specialized role in the pineal gland: efficiently O-methylating the N-acetylserotonin produced and released by β-pinealocytes, thereby improving the overall efficiency of melatonin synthesis. We have also identified transcriptomic changes that occur between night and day in seven cell types, the majority of which occur in β-pinealocytes and to a lesser degree in α-pinealocytes; many of these changes were mimicked by adrenergic stimulation with isoproterenol. The cellular heterogeneity of the pineal gland as revealed by this study provides a new framework for understanding pineal cell biology at single-cell resolution.

LIM homeobox transcription factor Isl1 is required for melatonin synthesis in the pig pineal gland.

Abstract: Melatonin is a key hormone that regulates circadian rhythms, metabolism, and reproduction. However, the mechanisms of melatonin synthesis and secretion have not been fully defined. The purpose of this study was to investigate the functions of the LIM homeobox transcription factor Isl1 in regulating melatonin synthesis and secretion in porcine pineal gland. We found that Isl1 is highly expressed in the melatonin-producing cells in the porcine pineal gland. Further functional studies demonstrate that Isl1 knockdown in cultured primary porcine pinealocytes results in the decline of melatonin and arylalkylamine N-acetyltransferase (AANAT) mRNA levels by 29.2% and 72.2%, respectively, whereas Isl1 overexpression raised by 1.3-fold and 2.7-fold. In addition, the enhancing effect of norepinephrine (NE) on melatonin synthesis was abolished by Isl1 knockdown. The in vivo intracerebroventricular NE injections upregulate Isl1 mRNA and protein levels by about threefold and 4.5-fold in the porcine pineal gland. We then examined the changes in Isl1 expression in the pineal gland and global melatonin levels throughout the day. The results show that Isl1 protein level at 24:00 is 2.5-fold higher than that at 12:00, which is parallel to melatonin levels. We further found that Isl1 increases the activity of AANAT promoter, and the effect of NE on Isl1 expression was blocked by an ERK inhibitor. Collectively, the results presented here demonstrate that Isl1 positively modulates melatonin synthesis by targeting AANAT, via the ERK signaling pathway of NE. These suggest that Isl1 plays important roles in maintaining the daily circadian rhythm.

β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes

Abstract: Melatonin (5-methoxy-N-acetylserotonin), the pineal hormone, is also synthesized by immune-competent cells The pineal hormone signals darkness, while melatonin synthesized on demand by activated macrophages at any hour of the day acts locally, favoring regulatory/tolerant phenotypes Activation of β-adrenoceptors in pinealocytes is the main route for triggering melatonin synthesis However, despite the well-known role of β-adrenoceptors in the resolution macrophage phenotype (M2), and the relevance of macrophage synthesized melatonin in facilitating phagocytic activity, there is no information regarding whether activation of β-adrenoceptors would induce melatonin synthesis by monocytes Here we show that catecholamines stimulate melatonin synthesis in bone marrow-derived dendritic cells and RAW 2647 macrophages Activation of β-adrenoceptors promotes the synthesis of melatonin by stimulating cyclic AMP/protein kinase A (PKA) pathway and by activating the nuclear translocation of NF-κB Considering the great number of macrophages around sympathetic nerve terminals, and the relevance of this system for maintaining macrophages in stages compatible to low-grade inflammation, our data open the possibility that extra-pineal melatonin acts as an autocrine/paracrine signal in macrophages under resolution or tolerant phenotypes

Rhythmic Regulation of Photoreceptor and RPE Genes Important for Vision and Genetically Associated With Severe Retinal Diseases

Abstract: Purpose The aim of the present study was to identify candidate genes for mediating daily adjustment of vision. Methods Genes important for vision and genetically associated with severe retinal diseases were tested for 24-hour rhythms in transcript levels in neuronal retina, microdissected photoreceptors, photoreceptor-related pinealocytes, and retinal pigment epithelium-choroid (RPE-choroid) complex by using quantitative PCR. Results Photoreceptors of wildtype mice display circadian clock-dependent regulation of visual arrestins (Arr1, Arr4) and the visual cycle gene Rdh12, whereas cells of the RPE-choroid exhibit light-dependent regulation of the visual cycle key genes Lrat, Rpe65, and Rdh5. Clock-driven rhythmicity of Arr1, Arr4, and Rdh12 was observed also in rat pinealocytes, to persist in a mouse model of diabetic retinopathy (db/db) and, in the case of Arr1, to be abolished in retinae of mice deficient for dopamine D4 receptors. Therefore, the expression rhythms appear to be evolutionary conserved, to be unaffected in diabetic retinopathy, and, for Arr1, to require dopamine signaling via dopamine D4 receptors. Conclusions The data of the present study suggest that daily adjustment of retinal function combines clock-dependent regulation of genes responsible for phototransduction termination (Arr1, Arr4) and detoxification (Rdh12) in photoreceptors with light-dependent regulation of genes responsible for retinoid recycling (Lrat, Rpe65, and Rdh5) in RPE. Furthermore, they indicate circadian and light-dependent regulation of genes genetically associated with severe retinal diseases.

Effect of Monochromatic Light on Circadian Rhythm of Clock Genes in Chick Pinealocytes.

Abstract: The avian circadian system is a complex of mutually coupled pacemakers residing in pineal gland, retina and suprachiasmatic nucleus. In this study, the self-regulation mechanism of pineal circadian rhythm was investigated by culturing chick primary pinealocytes exposed to red light (RL), green light (GL), blue light (BL), white light (WL) and constant darkness (DD), respectively. All illuminations were set up with a photoperiod of 12 light: 12 dark. The 24-h expression profiles of seven core clock genes (cBmal1/2, cClock, cCry1/2 and cPer2/3), cAanat and melatonin showed significant circadian oscillation in all groups, except for the loss of cCry1 rhythm in BL. Compared to WL, GL increased the amplitudes and mesors of positive elements (cClock and cBmal1/2) and reduced those of negative elements (cCry1/2 and cPer2/3), in contrast to RL. The temporal patterns of cAanatmRNA and melatonin secretion have always been consistent with the positive genes. Besides, GL advanced the acrophases of the positive elements, cAanat and melatonin, but RL and BL showed the opposite effect. Thereby, GL could promote the secretion of melatonin by enhancing the expressions of positive clock genes and repressing the expressions of negative clock genes.

Melatonin receptor (MTNR1A and MTNR2B) expression during the breeding season in the yak (Bos grunniens)

Abstract: Melatonin plays key roles in a wide range of mammalian body functions, which are mediated by the melatonin-specific cell surface receptor (MTNR1A and MTNR1B). To better understand the role of MTNR in the yak (Bos grunniens), we determined the melatonin receptor mRNA expression level. The analysis showed that the MTNR mRNA expression level was higher in the pineal gland tissue than in the hypothalamus, pituitary gland, and ovary ( P < 0.01) during the breeding season. Immunofluorescence analyses showed that yak MTNR was located in the pinealocyte, synaptic ribbon, and synaptic spherules of the pineal gland and that melatonin interacts via nerve fibres. In the hypothalamus, MTNR was located in the magnocellular neurons and parvicellular neurons. MTNR was localized in acidophilic cells and basophilic cells in the pituitary gland. In the ovary, MTNR was present in the ovarian follicle, corpus luteum, and Leydig cells. The domestic yak (Bos grunniens) is a rare bovine species found at high altitudes in the Qinghai- Tibetan Plateau and adjacent regions. Yaks have unique biological and economic characteristics that make them resistant to cold. They have evolved a unique body structure and physiological adapta - tion mechanisms. The reproductive mechanism may be the most important requirement for yak survival in this situation. The yak breeding season runs from July to January in China. This period is perfectly synchronized with the long nights and short days between the summer solstice and winter solstice. The pineal gland is the only endocrine organ that can transform light into endocrine informa - tion (Binkley, 1993). Melatonin is a polypeptide hormone, which is synthesized primarily in the pineal gland. The day length is the main factor to initiate the yak breeding season each year via melatonin. Melatonin has an important role in the maturation of oocytes where the melatonin

The environmental neurotoxin β-N-methylamino-L-alanine inhibits melatonin synthesis in primary pinealocytes and a rat model.

Abstract: The environmental neurotoxin β-N-methylamino-L-alanine (BMAA) is a glutamate receptor agonist that can induce oxidative stress and has been implicated as a possible risk factor for neurodegenerative disease. Detection of BMAA in mussels, crustaceans, and fish illustrates that the sources of human exposure to this toxin are more abundant than previously anticipated. The aim of this study was to determine uptake of BMAA in the pineal gland and subsequent effects on melatonin production in primary pinealocyte cultures and a rat model. Autoradiographic imaging of 10-day-old male rats revealed a high and selective uptake in the pineal gland at 30 minutes to 24 hours after 14 C-L-BMAA administration (0.68 mg/kg). Primary pinealocyte cultures exposed to 0.05-3 mmol/L BMAA showed a 57%-93% decrease in melatonin synthesis in vitro. Both the metabotropic glutamate receptor 3 (mGluR3) antagonist Ly341495 and the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate prevented the decrease in melatonin secretion, suggesting that BMAA inhibits melatonin synthesis by mGluR3 activation and PKC inhibition. Serum analysis revealed a 45% decrease in melatonin concentration in neonatal rats assessed 2 weeks after BMAA administration (460 mg/kg) and confirmed an inhibition of melatonin synthesis in vivo. Given that melatonin is a most important neuroprotective molecule in the brain, the etiology of BMAA-induced neurodegeneration may include mechanisms beyond direct excitotoxicity and oxidative stress.

Evaluation of human pineal gland acetylserotonin O-methyltransferase immunoreactivity in suicide: A preliminary study.

Abstract: Disorders of the serotonergic system are especially known to be present in the neurobiology of suicidal behavior Studies investigating melatonin levels show that changes in pineal gland functions

Noise Induces Hypothyroidism and Gonadal Dysfunction Via Stimulation of Pineal–Adrenal Axis in Chicks

Abstract: Noise is a world-wide problem that causes nervous, endocrine and cardiovascular disorders, and eventually health hazards in humans and animals. Objective of the current work is to investigate endocrine interaction in noise stress, which subsequently affects other endocrine functions including gonads in a poultry bird like chicks. Gravimetric, ultrastructural and hormonal status of the endocrine organs were examined to ascertain the effects of noise stress. Acute noise at 60 dB had no effect, but at 80 and 100 dB each for 3 h, increased pineal and serum serotonin, and adrenal and serum corticosterone, epinephrine and norepinephrine concentrations, without any change in thyroid or gonadal hormones. Chronic noise exposure at 60, 80 and 100 dB each for 6 h, daily for 7 days, drastically disturbed normal behavior, and quantum of food consumption and water intake. Chronic exposure also significantly decreased body weight including thyroid, ovary and testis weight, and increased adrenal weight. Noise stress caused ultrastructural changes leading to stimulations of pinealocytes (with abundance of rough endoplasmic reticulum and mitochondria), adrenocortical cells (enlarged nuclei and abundance of smooth endoplasmic reticulum) and adrenomedullary cells (enlarged nuclei with presence of chromaffin granules) were observed in noise stress. Additionally, pineal and serum serotonin, N-acetyl serotonin and melatonin, and adrenal and serum corticosterone, epinephrine and norepinephrine levels were significantly elevated following chronic noise exposure. Contrarily, thyroid activity was suppressed with atrophied thyroid follicles followed by declined levels of serum T3 and T4 with elevation of TSH level. Simultaneously, serum 17β-estradiol (E2) and testosterone (T) concentrations were also significantly declined in all the doses of chronic noise. These changes were dose dependent of noise exposure. The findings suggest that (a) adrenal and pineal glands respond primarily to noise and secondarily act on other endocrine organs including gonads in chicks, (b) adrenal directly and/or indirectly causes thyroid and gonadal dysfunctions via pineal following noise exposure in chicks.

Morphology and quantification of sheep pineal glands at pre-pubertal, pubertal and post-pubertal periods

Abstract: The pineal gland is a neuroendocrine organ associated with photoperiodic regulation in mammals. The aim of this study was to evaluate the pineal gland at the pre-pubertal, pubertal and post-pubertal periods by means of morphology and stereology. The study examined at total of 24 ovine pineal glands collected from healthy female Akkaraman breed. Thick sections (40 μm) were cut and treated with synaptophysin. Following each thick section, six consecutive sections at a thickness of 5 μm were cut. Each thin section was stained with one of the following dyes: Crossman's modified triple dye, glial fibrillary acidic protein (GFAP), melatonin marker, periodic acid-Schiff, Von Kossa and AgNOR. The pineal gland volume was measured using Cavalieri's method. The optical fractionator was used to estimate the total number of pinealocytes. The percentage of parenchyma and connective tissue and degree of vascularization were estimated by the area fraction fractionator method. The pineal gland volumes in the pre-pubertal, pubertal and post-pubertal groups were 7.53 ± 1.715 mm3 , 11.20 ± 1.336 mm3 and 17.75 ± 1.188 mm3 , respectively (p < .5). The number of pinealocytes in the pre-pubertal, pubertal and post-pubertal groups was 3,244,000 ± 228,076, 4,438,000 ± 243,610, 7,381,766 ± 406,223, respectively (p < .05). The glands of the post-pubertal group contained the highest amount of connective tissue (11.49 ± 2.103%; p < .5) and the largest GFAP staining area (p < .05). The melatonin staining density was the highest in the pubertal group. The density of lipofuscin staining was higher in the pubertal and post-pubertal groups.

Physiology, Pineal Gland

Abstract: The pineal gland is an endocrine gland located in the posterior aspect of the cranial fossa in the brain. Its importance is in the circadian cycle of sleep and wakefulness. The pineal gland is also known as the epiphysis cerebri. The gland is pine cone-shaped and about 0.8 cm long. In an adult, it weighs about 0.1 g. It is an unpaired gland that resides between the thalamic bodies behind the habenular commissure. It is located near the corpora quadrigemina, which is behind the third ventricle. Cerebrospinal fluid bathes the gland through the pineal recess.The following are the relations of the pineal gland in the brain on the coronal section: Superiorly: Corpus callosum (splenium aspect) Inferiorly: Inferior and superior colliculi Superolateral: Third ventricle choroid plexus In a sagittal section, the following is seen: Anterosuperior: Thalamus and the habenular commissure Anteroinferior: Cerebral aqueduct of Sylvius, posterior commissure, and the cerebral peduncle. Posterosuperior: Cerebral vein of Galen Inferiorly: Quadrigemineal plate The epiphysis cerebri is supplied by the adrenergic nerves. The neurons are sensitive to epinephrine. The sympathetic innervation is from the superior cervical ganglion, while the parasympathetic innervation is from the optic and pterygopalatine ganglia. The pineal stalk of the gland also has nerve fibers along with innervation from neurons from the trigeminal ganglion. The neurons from the trigeminal ganglion have nerve fibers that contain the PACAP, which is a neuropeptide. The blood supply of the pineal gland is derived from the posterior cerebral artery from its choroidal branches. The internal cerebral vein drains the blood from the epiphysis cerebri.Histologically the gland consists of cells called pinealocytes and supporting cells.

The pineal gland of the shrew (Blarina brevicauda and Blarina carolinensis): a light and electron microscopic study of pinealocytes

Abstract: The pineal gland structure and ultrastructure in the Northern (Blarina brevicauda) and Southern short-tailed shrew (Blarina carolinensis) are described by light and electron microscopy. Results observed were similar to other mammals of Insectivora described previously, specifically, the hedgehog (Erinaceus europaeus) and the Old World mole (Talpa europea). Two different types of pinealocytes were noticed by electron microscopy, in addition to relatively few glial cells. Granular vesicles were not noticed in abundance. The granular endoplasmic reticulum was observed and studded with vesicles. The golgi apparatus was well developed and appeared often. Synaptic ribbons were observed in several different formations consisting of ribbons and/or rods. The ciliary derivative, the rudimentary photoreceptor structures found in the pinealocytes of population I, was noticed in a 9 + 0 tubular pattern. Within these semifossorial shrews, the relationship between specific intracellular organelles and their function was discussed.

Protein and mRNA expression of gonadotropin-releasing hormone receptor in yaks during estrus

Abstract: To demonstrate the role of gonadotropin-releasing hormone (GnRH) in yaks (Bos grunniens), we characterized the expression of gonadotropin-releasing hormone receptor (GnRHR) mRNA and protein. The level of GnRHR mRNA in the hypothalamus was higher than that in the pineal gland, pituitary gland, and ovary during estrus. Immunofluorescence analysis showed that GnRHR was expressed in the pinealocyte, synaptic ribbon, and synaptic spherules of the pineal gland and that melatonin interacts with GnRHR via nerve fibers. In the hypothalamus, GnRHR was [...]

Infradian Rhythm of the Content of Secretory Granules in Pinealocyte Cytoplasm in Mice and Rats

Abstract: The numerical density of secretory granules dense-core vesicles (DCV) in the cytoplasm of pinealocytes of the pineal gland was estimated by transmission electron microscopy in male white mice and Wistar rats. The 3-day biorhythm and lunaphase changes in the DCV content in the perikaryon and the processes of pinealocytes, which are manifested significantly in different seasons of the year, are established. The three-day biorhythm in adult male mice in comparison with younger male rats is not expressed uniformly in different phases of the moon. The in-phase manifestation of infradian biorhythms in different species of animals during the year with an unchanged daily photophase indicates the existence of common external synchronizers for mammals of these biorhythms that are not associated with the light/dark cycle.