Showing papers on "Pinealocyte published in 2022"

Benefits and adverse events of melatonin use in the elderly (Review)

Abstract: Melatonin is a hormone secreted by the pineal gland in accordance with the circadian rhythm when the light level decreases. Reduction of melatonin secretion with age may be associated with physiological aging in neurodegenerative diseases by affecting the suprachiasmatic nucleus or of the neuronal pathways of transmission to the pineal gland. A significant decrease in melatonin synthesis has been reported in various disorders and diseases, including cardiovascular diseases, metabolic disorders (particularly diabetes type 2), cancer and endocrine diseases. In addition to the fact, that melatonin is a sleep inducer, it also exerts cytoprotective properties as an antioxidant and free radical scavenger. The therapeutic role of melatonin has been demonstrated in sleep disorders, eye damage and cardiovascular disease. The association between melatonin and β-blockers has had a positive impact on sleep disorders in clinical trials. Previous studies have reported the anti-inflammatory effect of melatonin by adjusting levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α. Melatonin treatment has been demonstrated to decrease IL-6 and IL-10 expression levels and efficiently attenuate T-cell proliferation. Currently, there is an inconsistency of scientific data regarding the lowest optimal dose and safety of melatonin for long-term use. The aim of the present review was to summarize the evidence on the role of melatonin in various clinical conditions and highlight the future research in this area.

Genetic ablation of the Bsx homeodomain transcription factor in zebrafish: Impact on mature pineal gland morphology and circadian behavior

Abstract: The pineal gland is a neuroendocrine structure in the brain, which produces and secretes the hormone melatonin at nighttime and is considered a key element in the circadian clock system. Early morphogenesis of the gland is controlled by a number of transcription factors, some of which remain active in adult life. One of these is the brain‐specific homeobox (Bsx), a highly conserved homeodomain transcription factor with a developmental role in the pineal gland of several species, including zebrafish, and regulatory roles in mature pinealocytes of the rat. To determine the role of Bsx in circadian biology, we here examined the effects of a bsx loss‐of‐function mutation on the pineal gland in adult zebrafish and on behavioral circadian rhythms in larvae. In pineal cell type‐specific Gfp/Egfp reporter zebrafish lines, we did not detect fluorescence signals in the pineal area of homozygous (bsx−/−) mutants. Interestingly, a nonpigmented area on the dorsal surface of the head above the gland, known as the pineal window, was pigmented in the homozygous mutants. Furthermore, a structure corresponding to the pineal gland was not detectable in the midline of the adult brain in histological sections analyzed by Nissl staining and S‐antigen immunohistochemistry. Moreover, the levels of pineal transcripts were greatly reduced in bsx−/− mutants, as revealed by quantitative real‐time polymerase chain reaction analysis. Notably, analysis of locomotor activity at the larval stage revealed altered circadian rhythmicity in the bsx mutants with periods and phases similar to wildtype, but severely reduced amplitudes in locomotor activity patterns. Thus, Bsx is essential for full development of the pineal gland, with its absence resulting in a phenotype of morphological pineal gland ablation and disrupted circadian behavior.

Digital histological morphometry of the human pineal gland in a postmortem study, with endocrine and neurological clinical implications

Abstract: The pineal gland is a small‐sized, photo neuroendocrine organ in the midline of the brain that synthesises and secretes melatonin and serotonin. Chords and islands of pinealocytes constitute the secretory parenchyma, while glial tissue and calcifications represent degenerative changes. This study examined human postmortem pineal glands to microscopically assess morphological changes possibly associated with clinical data, by using digital techniques. A retrospective autopsy study has been performed on 72 paediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with synaptophysin (SYN), neuron‐specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. The comorbidities used for correlation with morphometric data were obesity, type 2 diabetes, adrenal gland adenoma, goitre, chronic pancreatitis, arterial hypertension, and mixed dementia. Thirty‐three females and 39 males were included in the study. Increased secretory parenchyma was found in patients with chronic pancreatitis, arterial hypertension, and adrenal gland adenoma. Reduced activity was found in patients with type 2 diabetes, obesity, advanced pineal calcification, mixed dementia, and old age. There were no changes associated with goitre, cachexia, or Willis's polygon atherosclerosis. No significant differences between gender were found. The activity of the pineal gland can be assessed by quantitative immunohistochemistry of neuroendocrine and structural pinealocyte markers and observation of glial tissue and calcifications. There is a need for further research to evaluate the clinical impact of these morphological changes on the neuroendocrine systems, with clinical implications in endocrinology, neurology, and even psychiatry. Digital techniques offer a more exact analysis of histological data.

Spatio-temporal dynamics of nuclear CREB1: what does it mean?

Abstract: In the mammalian pineal gland (PG), cyclic AMP responsive element-binding protein 1 (CREB1) participates in the nocturnal melatonin synthesis that rhythmically modulates physiology and behavior. Phosphorylation of CREB1 present in pinealocyte nuclei is one of the key regulatory steps that drives pineal transcription. The spatio-temporal dynamics of CREB1 itself within PG cell types have not yet been documented. In this study we analyzed total CREB1 via Western blot, and the dynamism of CREB1 nuclear distribution in individual rat pinealocytes using fluorescence immunohistochemistry followed by confocal laser-scanning microscopy and quantitative analysis. Total CREB1 levels remained constant in the PG throughout the light:dark cycle. The distribution pattern of nuclear CREB1 did vary, however, among different PG cells. Pinealocytes emerged as having discrete CREB1 domains within their nucleoplasm that were especially distinct. The number, size, and location of CREB1 foci fluctuated among pinealocytes, within the same PG and among Zeitgeber times. A significantly larger dispersion of CREB1-immunoreactive nuclear sites was found at night. This was not accompanied by changes in the overall transcription activity, which was mostly conserved between the light and dark phases, as shown by the expression of a particular phosphorylated form of the RNA polymerase II (RNAPII-pSer5CTD). Suppression of the nocturnal norepinephrine pulse by chronic bilateral superior cervical ganglionectomy increased CREB1 dispersion in pinealocyte nuclei, as compared to sham-derived cells. In addition, differences in CREB1 distribution were found between sham-operated and non-operated rats at early night. Together, these data suggest that in mature pinealocytes nuclear CREB1 is subjected to a dynamic spatio-temporal distribution. Further studies are necessary to elucidate the underlying mechanisms, including the role of chromatin and interchromatin elements, and to understand the impact of CREB1 reorganization in the pineal transcriptome.

Anatomical and histological investigation of the pineal gland in the lake van fish (Alburnus tarichi (Güldenstädt, 1814))

Abstract: The pineal gland and melatonin secreted from the gland regulate the biological clock and adaptation to seasonal changes, glucose balance, nutrition and locomotor activities. In this study, the pineal gland of the Lake Van fish was examined anatomically and histologically. The melatonin level secreted from the pineal gland was determined in fish plasma sampled from both lakes and streams during reproduction migration. The pineal gland in the Lake Van fish, as in other teleost fish, is located in the head, under the translucent pineal window, which does not contain many pigment cells. The gland consists of pineal vesicle and pineal stalk parts on the dorsal sac in the Lake Van fish. It was determined that the pineal gland showed good vascularity. The presence of pinealocytes and different types of cells in the pineal organ was determined histologically. Pinealocytes were intensely localized in the lumen of the pineal vesicle. The plasma melatonin level increased in fish passing from lake to stream for reproductive migration.

Profiling Temporal Changes of the Pineal Transcriptomes at Single Cell Level Upon Neonatal HIBD

Abstract: Neonatal hypoxic-ischemic brain damage (HIBD) often results in various neurological deficits. Among them, a common, yet often neglected, symptom is circadian rhythm disorders. Previous studies revealed that the occurrence of cysts in the pineal gland, an organ known to regulate circadian rhythm, is associated with circadian problems in children with HIBD. However, the underlying mechanisms of pineal dependent dysfunctions post HIBD remain largely elusive. Here, by performing 10x single cell RNA sequencing, we firstly molecularly identified distinct pineal cell types and explored their transcriptome changes at single cell level at 24 and 72 h post neonatal HIBD. Bioinformatic analysis of cell prioritization showed that both subtypes of pinealocytes, the predominant component of the pineal gland, were mostly affected. We then went further to investigate how distinct pineal cell types responded to neonatal HIBD. Within pinealocytes, we revealed a molecularly defined β to α subtype conversion induced by neonatal HIBD. Within astrocytes, we discovered that all three subtypes responded to neonatal HIBD, with differential expression of reactive astrocytes markers. Two subtypes of microglia cells were both activated by HIBD, marked by up-regulation of Ccl3. Notably, microglia cells showed substantial reduction at 72 h post HIBD. Further investigation revealed that pyroptosis preferentially occurred in pineal microglia through NLRP3-Caspase-1-GSDMD signaling pathway. Taken together, our results delineated temporal changes of molecular and cellular events occurring in the pineal gland following neonatal HIBD. By revealing pyroptosis in the pineal gland, our study also provided potential therapeutic targets for preventing extravasation of pineal pathology and thus improving circadian rhythm dysfunction in neonates with HIBD.

ETMR-14. The single-cell landscape of pineoblastoma identifies developmental origins and exposes novel therapeutic vulnerabilities.

Abstract: Abstract Pineoblastoma (PB) is a rare and aggressive childhood brain tumor with highly variable age and treatment-associated outcomes. Our recent bulk tumor analyses of DNA methylation and mutational landscapes uncovered four discrete PB molecular subgroups (PB-miRNA1, PB-miRNA2, PB-MYC/FOXR2, and PB-RB), providing a major advance in our understanding of biological and clinical heterogeneity. However, developmental origins of PB subgroup heterogeneity and mechanisms governing how specific genetic alterations promote malignancy remain unknown. To resolve the cellular origins of PB, we assembled a large single-nucleus RNA-sequencing cohort (n=32) of primary PB tumors, including representatives from each subgroup. Transcriptomic analysis identified subgroup-specific gene expression programs driving intra-tumoral heterogeneity. In addition, we discovered substantial differences in the expression of miRNA biogenesis genes between the PB-miRNA1 and PB-miRNA2 subgroups, providing mechanistic support for their distinct subgroup identities despite overlapping driver events. The MYC/FOXR2 subgroup was characterized by over-expression of the FOXR2 proto-oncogene in bulk RNA-seq, which we validated in single-nuclei and identified co-expressed downstream target genes. To map PB subgroups to their putative developmental beginnings, we created a single-cell transcriptional atlas of the murine pineal gland across 11 developmental stages (E11-P21). Trajectory inference within the developing pineal gland revealed a differentiation continuum of early, mid, and mature alpha-/beta pinealocytes. Cross-species correlation and deconvolution identified significant associations between multiple PB subgroups and specific differentiation states of the pinealocyte lineage, suggestive of developmental origins. Characterization of pinealocyte development informed generation of biologically faithful disease models, including a novel genetically engineered mouse model of the PB-RB subgroup. PB-Rb1 mouse tumors were histologically and molecularly validated for their fidelity to human tumor counterparts, exhibiting up-regulation of key pinealocyte lineage markers that are diagnostic in patients. Finally, high-throughput drug screening identified several promising pharmacological candidates that may attenuate consequences of Rb1 deficiency in affected children.

The pineal gland

Abstract: The pineal gland was identified as a distinct structural component of the vertebrate brain for several centuries prior to its description in the human by Galen of Pergamon (c.130–200). It is now understood that the main function of the pineal is to receive information about the current state of the light–dark cycle from the environment and convey this information through the secretion of the hormone melatonin to the internal physiological systems of the body. Relative to other endocrine and neuroendocrine systems, the pineal gland has undergone a great deal of change during its evolutionary development. In cold-blooded vertebrates the cells of the pineal gland include photoreceptors that contact neurons to communicate with other organs in the body. The avian pineal gland is also a directly photosensory organ and secretes melatonin in response to this signal. In mammals, pinealocytes producing melatonin have replaced photoreceptors and the gland receives its information about light and darkness from the retina through multiple neuronal connections. Melatonin is secreted during the dark period of the day and, through its elevated blood levels, informs, through specific cell receptors, the peripheral organs and tissues regarding the light/dark cycle. In addition to its function of sending information to the periphery regarding light and dark, melatonin from the pineal gland also contributes to the entrainment of the central suprachiasmatic nuclei oscillator to the light–dark cycle. This chapter covers the anatomical features of the pineal gland, the synthesis and secretion of melatonin, the biological actions of melatonin, and various clinical aspects related to the pineal gland.

Biochemistry and Antioxidant Effects of Melatonin

Abstract: Melatonin (N-acetyl-5-methoxy-tryptamine) is a hormone taking place in many biological and physiological processes, such as reproduction, sleep, antioxidant effect, and circadian rhythm (biological clock), and is a multifunctional indolamine compound synthesized mainly from the metabolism of tryptophan via serotonin in the pineal gland. Melatonin, which is a hormone synthesized from the essential amino acid tryptophan, is substantially secreted from the pineal gland between the cerebral hemispheres found in the mammalian brain. In addition to this, it is also produced in the cells and tissues, such as the gastrointestinal system, gall, epithelial hair follicles, skin, retina, spleen, testis, salivary glands, bone marrow, leukocytes, placenta, and thrombocytes. It plays a role in many physiological events, such as synchronizing circadian rhythms, reproduction, fattening, molting, hibernation, and change of pigment granules, preserving the integrity of the gastrointestinal system with an anti-ulcerative effect in tissues and organs from which it is produced. Melatonin is also a powerful antioxidant and anti-apoptotic agent that prevents oxidative and nitrosative damage to all macromolecules due to its ability to form in metabolic activities, directly excrete toxic oxygen derivatives, and reduce the formation of reactive oxygen and nitrogen species. In this book chapter, we will explain the structure, synthesis, metabolism, and antioxidant effects of the melatonin hormone.

Melatonin

Abstract: Melatonin, known as a hormone specific to the pineal gland, is also produced in other organs of the body such as the retina and gastrointestinal tract (GI), and is much more abundant in the GI compared to the pineal gland. Melatonin in the pineal gland plays an important role in the circadian rhythm, while extra-pineal melatonin does not play such a role and acts as a potent antioxidant. Due to its dual lipophilic and hydrophilic properties, this indoleamine crosses all the barriers within the body and exerts its effects through MT1 and MT2 receptors. Melatonin exerts its antioxidant effects directly and indirectly, and plays an important antioxidant role by increasing the expression and function of antioxidants and reducing the expression of genes involved in the production of free radicals. In addition to studies on the effects of melatonin on sleep disorders, the role of this potent antioxidant in many diseases including inflammation, neurodegenerative diseases, gastrointestinal diseases and cancer has been investigated and its significant effects on patients’ health have been observed. Accordingly, in this chapter we will review the properties of melatonin as an antioxidant and its beneficial effects in various diseases.

Adrenal Glands, Pineal Gland, and the Circadian Rhythm: Structure and Physiology

Abstract: The adrenal glands are located at the top of each kidney towards the front and weighs around 5 g. Each gland measures 4 cm, weighs 4–5 g, and has a thickness of 3 cm. The adrenal glands are highly vascularized and divided anatomically and physiologically into two different areas in terms of blood supply, innervation, and functions. Each gland consists of three different structures regarding origin, anatomy, histology, physiology, and regulation. The adrenal cortex comprises three zones: the glomerulosa, the fasciculata, and the reticularis, they produce mineralocorticoids, glucocorticoids, and adrenal sex hormones, respectively. A novel zone has been identified between the glomerulosa and the fasciculata zones and this zone was titled as undifferentiated cell zone, where cells can proliferate and migrate bidirectionally to zona glomerulosa and to zona fasciculata centripetally. The pineal gland is called pineal body that is attached to the posterior aspect of the third ventricle by means of a short stem containing sympathetic neural axes penetrating the gland tissue which is connected to the hypothalamus. It contains many cells such as pinealocytes, neuroglial cells, interstitial cells, perivascular phagocytes. Pineal gland produces hormones such as melatonin, serotonin, many polypeptides and indoles. The pineal gland adjusts the function of many endocrine glands. The main physiological function of melatonin is to transfer information of the daily cycle of day and night to body systems to organize the functions that respond to photoperiod alteration which includes the cyclic rhythms. Daily melatonin is secreted as a night signal to organize, stabilize, and support combination circadian rhythms such as core temperature, sleep-wake rhythms. This organization for other physiological functions like antioxidant, immunity, glucose, and homeostasis depends on the melatonin signal. This chapter discusses the topics related to adrenal glands, pineal gland, and circadian rhythm.KeywordsAdrenal glandsPineal glandCircadian rhythmStructure and physiology

Morphological study of the pineal gland of Alouatta belzebul

Abstract: ABSTRACT The pineal is a neuroendocrine gland responsible for the synthesis and release of melatonin. It is present in the brain of vertebrates, but its morphology and location vary considerably among species. For the species Alouatta belzebul, although some anatomical aspects of the nervous system have been described, there is no information on the morphology and histological composition of this gland. Thus, the present study aimed to describe the morphological, morphometric, and histological aspects of the pineal of Alouatta belzebul. Seven adult specimens were dissected from which the location of the gland in relation to the surrounding brain structures was described, and its length and width were measured. Histological slides were then prepared and stained using hematoxylin-eosin and PAS techniques. It was observed that the pineal of Alouatta belzebul is located superior and cranial to the cerebellum, superior to the superior colliculi and below the splenium of the corpus callosum and was classified as sub-callosal. It had an average length of 2.6mm and an average width of 1.14mm. Histologically the gland is composed of irregular strands of pinealocytes and gliocytes. The pinealocytes showed pigments similar to melanin.

A Response of the Pineal Gland in Sexually Mature Rats under Long-term Exposure to Heavy Metal Salts.

Abstract: Pollution with heavy metal salts is an important environmental problem today, having an adverse effect on public health. The endocrine system maintains homeostasis in the body. The antioxidant protection (GPX-1) of the pineal gland in mature rats was studied. Animals of the experimental group represented a model of microelementosis, achieved by adding a mixture of heavy metal salts for 90 days to drinking water: zinc (ZnSO4×7H2O) - 5 mg/l, copper (CuSO4×5H2O) - 1 mg/l, iron (FeSO4) - 10 mg/l, manganese (MnSO4×5H2O) - 0.1 mg/l, lead (Pb(NO3)2) - 0.1 mg/l, and chromium (K2Cr2O7) - 0.1 mg/l. Morphological, statistical and immunohistochemical (GPX-1) research methods were used. Long-term (90-days) intake of heavy metal salts mixture in the body of experimental animals brought about development of the general adaptation syndrome, the stage of chronic stress "subcompensation" in the pineal gland. Morphological rearrangements were of nonspecific polymorphic nature as severe hemodynamics disorder in the organ, impairment of vascular wall morphology, development of tissue hypoxia and oxidative stress, accompanied by processes of accelerated apoptosis in part of pinealocytes, by a significant decrease in glutathione peroxidase level in the organ and reactive astrogliosis as a response to the damaging agent's action. Along with the negative changes in the pineal gland, a compensatory-adaptive processes with signs of functional stress also occurred. A sufficiently high degree of glutathione peroxidase activity in 39% of pinealocytes located perivascularly, active adaptive glial reaction and activation of synthetic processes in some pinealocytes were also observed.

RNA Sequencing of Single Pineal Cells.

Abstract: The pineal gland presents a powerful genetic tool to study a broad range of physiological processes. It has been instrumental as a model in understanding transduction processes and daily changes in gene expression and holds great promise in understanding development. Currently, the field is at an exciting point, with methods available for the isolation of individual cells and, as presented here, the preparation of these single cells for sequencing. The resulting cellular transcriptomes have played a role in categorizing cells in the pineal gland, with current estimates including two types of pinealocytes, three types of astrocytes, two types of microglia, and two types of endothelial cells, including the poorly understood vascular and meningeal cell. The methods described in this chapter will serve to support and advance cellular studies of the pineal gland in the twenty-first century.