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Anatomia, Histologia, Embryologia Jul 2022The pineal gland and melatonin secreted from the gland regulate the biological clock and adaptation to seasonal changes, glucose balance, nutrition and locomotor...
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.
Topics: Animals; Fishes; Lakes; Melatonin; Pineal Gland; Rivers
PubMed: 35285548
DOI: 10.1111/ahe.12802 -
Journal of Analytical Toxicology Oct 2022Since 2015, the North Carolina Office of the Chief Medical Examiner has investigated seven deaths of infants and toddlers, aged 2 months to 3 years, with exogenous...
Since 2015, the North Carolina Office of the Chief Medical Examiner has investigated seven deaths of infants and toddlers, aged 2 months to 3 years, with exogenous melatonin detected upon toxicological analysis. Melatonin concentrations ranged from 3 to 1,400 ng/mL in postmortem whole blood. While the cause and the manner of all seven deaths were classified as undetermined, the analytical findings are noteworthy. Melatonin is generally considered a safe, natural product appearing in many over-the-counter supplements geared toward young children to facilitate calmness and improve sleep. Melatonin is a neurohormone, which regulates not only circadian rhythms and natural sleep but also other physiological functions. Endogenous melatonin production, derived from essential amino acid metabolism, does not begin until pineal gland maturation at ∼3 months of age with concentrations in plasma peaking during periods of darkness at ∼0.2 ng/mL. Administering commercially available melatonin supplements to infants results in levels substantially greater than endogenous sources, which should not be assumed to be safe just because of their endogenous nature. The finding of exogenous concentrations in some postmortem pediatric cases warrants attention. Several topics of interest surrounding these postmortem melatonin findings will be considered, such as minimal regulatory control over commercial products as well as the potential impact on hazardous sleeping conditions. This manuscript will outline the physiological effects of melatonin and detail the case studies from the North Carolina medical examiner system. Forensic toxicology laboratories should consider including melatonin at exogenous concentrations in their testing schemes for appropriate postmortem infant and toddler cases.
Topics: Amino Acids, Essential; Biological Products; Child; Child, Preschool; Dietary Supplements; Humans; Infant; Melatonin; Pineal Gland
PubMed: 35639879
DOI: 10.1093/jat/bkac033 -
Journal of Pineal Research Dec 2023Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating...
Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating melatonin levels. Melatonin is a potent antioxidant and exogenous melatonin treatment is neuroprotective in experimental HD models. In neurons, melatonin is exclusively synthesized in the mitochondrial matrix. Thus, we investigated the integrity of melatonin biosynthesis pathways in pineal and extrapineal brain areas in human HD brain samples, in the R6/2 mouse model of HD and in full-length mutant huntingtin knock-in cells. Aralkylamine N-acetyltransferase (AANAT) is the rate-limiting step enzyme in the melatonin biosynthetic pathway. We found that AANAT expression is significantly decreased in the pineal gland and the striatum of HD patients compared to normal controls. In the R6/2 mouse forebrain, AANAT protein expression was decreased in synaptosomal, but not nonsynaptosomal, mitochondria and was associated with decreased synaptosomal melatonin levels compared to wild type mice. We also demonstrate sequestration of AANAT in mutant-huntingtin protein aggregates likely resulting in decreased AANAT bioavailability. Paradoxically, AANAT mRNA expression is increased in tissues where AANAT protein expression is decreased, suggesting a potential feedback loop that is, ultimately unsuccessful. In conclusion, we demonstrate that pineal, extrapineal, and synaptosomal melatonin levels are compromised in the brains of HD patients and R6/2 mice due, at least in part, to protein aggregation.
Topics: Humans; Mice; Animals; Melatonin; Huntington Disease; Pineal Gland
PubMed: 37721126
DOI: 10.1111/jpi.12909 -
Psychiatry Research. Neuroimaging Jul 2019Patients with major depressive disorder (MDD) often have circadian rhythm alteration and sleep disturbance. The pineal gland regulates the circadian rhythm and sleep by...
Patients with major depressive disorder (MDD) often have circadian rhythm alteration and sleep disturbance. The pineal gland regulates the circadian rhythm and sleep by the secretion of melatonin neurohormone. However, the relationship between pineal abnormality and MDD remains elusive. 50 patients with MDD and 35 gender- and age-matched healthy controls underwent high-resolution structural MRI. Pineal parenchymal volume (PPV) was measured manually. Inter-group differences in prevalence of pineal cyst and PPV were examined. In addition, we investigated the correlations between PPV and symptom severity as well as sleep variables in the patient group. Compared to healthy controls, patients with MDD had a higher prevalence of pineal cyst. Moreover, patients had significantly decreased PPV relative to controls. However, no significant correlations were observed between PPV and symptom severity as well as sleep variables. Our findings suggest that pineal abnormality may play a critical role in depression.
Topics: Adolescent; Adult; Cysts; Depressive Disorder, Major; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pineal Gland; Young Adult
PubMed: 31121531
DOI: 10.1016/j.pscychresns.2019.05.004 -
British Journal of Pharmacology Aug 2018Melatonin 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... (Review)
Review
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.
Topics: Animals; Humans; Immunity, Innate; Inflammation; Melatonin; Neoplasms; Phagocytes; Pineal Gland
PubMed: 29105727
DOI: 10.1111/bph.14083 -
Journal of Pineal Research Jan 2024Immune-pineal axis activation is part of the assembly of immune responses. Proinflammatory cytokines inhibit the pineal synthesis of melatonin while inducing it in...
Immune-pineal axis activation is part of the assembly of immune responses. Proinflammatory cytokines inhibit the pineal synthesis of melatonin while inducing it in macrophages by mechanisms dependent on nuclear factor-κB (NF-κB) activation. Cytokines activating the Janus kinase/signal transducer and activator of transcription (STAT) pathways, such as interferon-gamma (IFN-γ) and interleukin-10 (IL-10), modulate melatonin synthesis in the pineal, bone marrow (BM), and spleen. The stimulatory effect of IFN-γ upon the pineal gland depends on STAT1/NF-κB interaction, but the mechanisms controlling IL-10 effects on melatonin synthesis remain unclear. Here, we evaluated the role of STAT3 and NF-κB activation by IL-10 upon the melatonin synthesis of rats' pineal gland, BM, spleen, and peritoneal cells. The results show that IL-10-induced interaction of (p)STAT3 with specific NF-κB dimmers leads to different cell effects. IL-10 increases the pineal's acetylserotonin O-methyltransferase (ASMT), N-acetylserotonin, and melatonin content via nuclear translocation of NF-κB/STAT3. In BM, the nuclear translocation of STAT3/p65-NF-κB complexes increases ASMT expression and melatonin content. Increased pSTAT3/p65-NF-κB nuclear translocation in the spleen enhances phosphorylated serotonin N-acetyltransferase ((p)SNAT) expression and melatonin content. Conversely, in peritoneal cells, IL-10 leads to NF-κB p50/p50 inhibitory dimmer nuclear translocation, decreasing (p)SNAT expression and melatonin content. In conclusion, IL-10's effects on melatonin production depend on the NF-κB subunits interacting with (p)STAT3. Thus, variations of IL-10 levels and downstream pathways during immune responses might be critical regulatory factors adjusting pineal and extra-pineal synthesis of melatonin.
Topics: Rats; Animals; NF-kappa B; Pineal Gland; Melatonin; Interleukin-10; Signal Transduction
PubMed: 37990784
DOI: 10.1111/jpi.12923 -
The European Journal of Neuroscience Jun 2017Several cell types in the pineal gland are known to establish intercellular gap junctions, but the connexin constituents of those junctions have not been fully...
Several cell types in the pineal gland are known to establish intercellular gap junctions, but the connexin constituents of those junctions have not been fully characterized. Specifically, the expression of connexin36 (Cx36) protein and mRNA has been examined in the pineal, but the identity of cells that produce Cx36 and that form Cx36-containing gap junctions has not been determined. We used immunofluorescence and freeze fracture replica immunogold labelling (FRIL) of Cx36 to investigate the cellular and subcellular localization of Cx36 in the pineal gland of adult mouse and rat. Immunofluorescence labelling of Cx36 was visualized exclusively as puncta or short immunopositive strands that were distributed throughout the pineal, and which were absent in pineal sections from Cx36 null mice. By double immunofluorescence labelling, Cx36 was localized to tryptophan hydroxylase-positive and 5-hydroxytryptamine-positive pinealocyte cell bodies and their large initial processes, including at intersections of those processes and at sites displaying a confluence of processes. Labelling for the cell junction marker zonula occludens-1 (ZO-1) either overlapped or was closely associated with labelling for Cx36. Pinealocytes thus form Cx36-containing gap junctions that also incorporate the scaffolding protein ZO-1. FRIL revealed labelling of Cx36 at ultrastructurally defined gap junctions between pinealocytes, most of which was at gap junctions having reticular, ribbon or string configurations. The results suggest that the endocrine functions of pinealocytes and their secretion of melatonin is supported by their intercellular communication via Cx36-containing gap junctions, which may now be tested by the use of Cx36 null mice.
Topics: Animals; Connexins; Gap Junctions; Male; Mice; Mice, Inbred C57BL; Pineal Gland; Rats; Rats, Sprague-Dawley; Gap Junction delta-2 Protein
PubMed: 28474748
DOI: 10.1111/ejn.13602 -
European Spine Journal : Official... Jan 2023Adolescent idiopathic scoliosis (AIS) is believed to be caused by genetic, neurological, osseous growth anomalies, histological variables including muscle fiber...
PURPOSE
Adolescent idiopathic scoliosis (AIS) is believed to be caused by genetic, neurological, osseous growth anomalies, histological variables including muscle fiber percentage and core structure changes, metabolic and hormonal dysfunction, vestibular dysfunction, and platelet microarchitecture. The objective of this study was to contribute to the determination of the cause of AIS by analyzing the changes in pineal gland volume in AIS cases.
METHODS
Study (AIS) and control group were each comprised of 26 patients who met the inclusion requirements. Scoliosis radiograph and MRI of the pineal glands were used for radiological examinations. The distribution of age, gender, Risser grading for skeletal radiological development, and sexual maturation according to Tanner categorization were uniform and statistically insignificant between groups.
RESULTS
When the pineal gland volumes of the cases were evaluated according to age, the AIS group was found to have significantly reduced pineal gland volumes in all age groups. The pineal gland volume was found to be 38.1% lower in the AIS group compared to the control group (p˂0.001). In the AIS group, patients aged 13 years had the lowest pineal gland volume (77.2 ± 13.86 mm), while patients aged 15 years had the highest volume (97.9 ± 16.47 mm).
CONCLUSION
Changes in pineal gland volume support the role of the pineal gland in the etiopathogenesis of AIS.
Topics: Adolescent; Humans; Scoliosis; Pineal Gland; Kyphosis; Magnetic Resonance Imaging
PubMed: 36374335
DOI: 10.1007/s00586-022-07452-z -
Current Medicinal Chemistry 2023Melatonin, mainly released from the pineal gland, also produced in the reproductive organs and cells, plays important roles in rhythms of the sleep-wake cycle,... (Review)
Review
Melatonin, mainly released from the pineal gland, also produced in the reproductive organs and cells, plays important roles in rhythms of the sleep-wake cycle, retardation of ageing processes, and antioxidant/anti-inflammatory functions. As a key mediator in reproductive systems, melatonin is participated in the reproductive process via regulating gamete and embryo development and influences reproductive diseases and pregnancy outcomes. The underlying mechanisms include epigenetic and other regulations, which are interesting for exploring new targets in the prevention and treatment of reproductive diseases. This review discusses the relationship between melatonin and reproductive functions and dysfunction, as well as potential clinical applications of melatonin in reproductive medicine. Notably, Developmental Origins of Health and Diseases (DOHaD) is closely linked to reproduction, this article is the first to review the new progress in studies on the possible relationship between melatonin and DOHaD.
Topics: Pregnancy; Female; Humans; Melatonin; Pineal Gland; Reproduction; Antioxidants; Reproductive Medicine; Circadian Rhythm
PubMed: 36200146
DOI: 10.2174/0929867329666221005101031 -
Aging Jan 2020We aimed to investigate the association of pineal gland volume with the risk of isolated rapid eye movement (REM) sleep behavior disorder (RBD). We enrolled 245...
We aimed to investigate the association of pineal gland volume with the risk of isolated rapid eye movement (REM) sleep behavior disorder (RBD). We enrolled 245 community-dwelling cognitively normal elderly individuals without major psychiatric or neurological disorders at the baseline evaluation, of whom 146 completed the 2-year follow-up evaluation. We assessed RBD symptoms using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and defined probable RBD (pRBD) as an RBDSQ score of ≥ 5. We manually segmented the pineal gland on 3T T1-weighted brain magnetic resonance imaging and estimated its volume. The smaller the baseline pineal gland volume, the more severe the RBD symptoms at baseline. The individuals with isolated pRBD showed smaller pineal gland volumes than those without isolated pRBD. The larger the baseline pineal gland volume, the lower the risks of prevalent isolated pRBD at the baseline evaluation and incident isolated pRBD at the 2-year follow-up evaluation. Pineal gland volume showed good diagnostic accuracy for prevalent isolated pRBD and predictive accuracy for incident isolated pRBD in the receiver operator characteristic analysis. Our findings suggest that pineal gland volume may be associated with the severity of RBD symptoms and the risk of isolated RBD in cognitively normal elderly individuals.
Topics: Age Factors; Aged; Aged, 80 and over; Aging; Disease Susceptibility; Female; Humans; Incidence; Male; Organ Size; Pineal Gland; Prevalence; REM Sleep Behavior Disorder; ROC Curve; Risk Assessment; Risk Factors
PubMed: 31918412
DOI: 10.18632/aging.102661