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General and Comparative Endocrinology Mar 2021After being discovered from the bovine pineal gland by Aaron Lerner and co-workers in the year 1958, various distinguished researchers have reported melatonin... (Review)
Review
After being discovered from the bovine pineal gland by Aaron Lerner and co-workers in the year 1958, various distinguished researchers have reported melatonin (5-methoxy-N-acetyl-tryptamine) from several extra-pineal sources, including the gastrointestinal tract (GIT). In the year 1974, Raikhlin and Kvetnoy first detected this molecule in the gastrointestinal tissue. Later, within the last 45 years, many renowned investigators found that the GIT is a rich source of melatonin, in addition to the pineal gland. In the carp gut, the estimation of Arylalkylamine-N-acetyltransferase (AANAT) mRNA/protein levels, which is the rate-determining enzyme for melatonin biosynthesis in the pineal gland, confirmed the endogenous synthesis of melatonin. The remarkable feature of the pineal gland melatonin is its rhythmic synthesis with a peak at dark-phase and lowest at light-phase in synchronization with seasonal environmental light-dark (LD) cycle. Recent studies on carp demonstrated that the melatonin concentrations and the AANAT protein intensities in different gut segments underwent significant daily fluctuations. However, compared to the melatonin rhythm in the pineal gland, the melatonin profiles in gut tissue displayed daily rhythm in parallel with the feeding cycle of the carp, irrespective of LD conditions of the environment. Notably, in carp, the temporal pattern of the gut melatoninergic system found to vary with the environmental non-photic signal(s), such as food entrainment factors (viz. availability of food, timing of food supply, number(s) of feed per day, quality of food) those act as the most dependable synchronizer(s) in daily rhythm characteristics of gut melatonin and AANAT. Thereby in this review, it appears meaningful to highlight the existing data on the mode of synthesis of melatonin in cells of the digestive tract, and most importantly, the regulation of its synthesis. Finally, in comparison with the dynamic actions of melatonin derived from the pineal gland, this review will lead to underline the role of gut-derived melatonin in a variety of physiological functions.
Topics: Animals; Arylalkylamine N-Acetyltransferase; Circadian Rhythm; Humans; Intestines; Melatonin; Photoperiod; Pineal Gland
PubMed: 33309697
DOI: 10.1016/j.ygcen.2020.113693 -
Development (Cambridge, England) Jul 2018Neuroendocrine cells in the pineal gland release melatonin during the night and, in teleosts, are directly photoreceptive. During development of the pineal complex, a...
Neuroendocrine cells in the pineal gland release melatonin during the night and, in teleosts, are directly photoreceptive. During development of the pineal complex, a small number of cells migrate leftward away from the pineal anlage to form the parapineal cell cluster, a process that is crucial for asymmetrical development of the bilateral habenular nuclei. Here, we show that, throughout zebrafish embryonic development, the () gene is expressed in all cell types of the pineal complex. We identified Bmp and Noto/Flh as major regulators of expression in the pineal complex. Upon loss of Bsx through the generation of a targeted mutation, embryos fail to form a parapineal organ and develop right-isomerized habenulae. Crucial enzymes in the melatonin biosynthesis pathway are not expressed, suggesting the absence of melatonin from the pineal gland in mutants. Several genes involved in rod-like or cone-like phototransduction are also abnormally expressed, indicating that Bsx has a pivotal role in the differentiation of multiple cell types in the zebrafish pineal complex.
Topics: Animals; Cell Differentiation; Gene Expression Regulation, Developmental; Homeodomain Proteins; Melatonin; Pineal Gland; Zebrafish; Zebrafish Proteins
PubMed: 29945867
DOI: 10.1242/dev.163477 -
Journal of Neuro-oncology Nov 2016The extensive variety of possible histologic subtypes makes it imperative to establish a tissue diagnosis in patients with pineal region tumors. Management decisions... (Review)
Review
The extensive variety of possible histologic subtypes makes it imperative to establish a tissue diagnosis in patients with pineal region tumors. Management decisions regarding adjuvant therapy, prognosis, and follow-up strategies vary with the histologic diagnosis. Specialized surgical and stereotactic techniques have evolved to provide the neurosurgeon with an array of safe and effective options for obtaining a tissue diagnosis. Advanced microsurgical techniques combined with improved preoperative management and postoperative critical care methods have made aggressive surgical resection a mainstay of management. Aggressive surgical resection has resulted in excellent long-term prognoses for nearly all patients with benign tumors and a large percentage of patients with malignant tumors. However, pineal region surgery remains fraught with potential pitfalls, and these favorable results are dependent on an advanced level of surgical expertise.
Topics: Brain Neoplasms; Humans; Microsurgery; Neurosurgical Procedures; Pineal Gland; Pinealoma; Postoperative Complications; Treatment Outcome
PubMed: 27193692
DOI: 10.1007/s11060-016-2138-5 -
European Journal of Radiology Feb 2023To evaluate the effectiveness of diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) for differentiation between germinoma and other pineal region...
PURPOSE
To evaluate the effectiveness of diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) for differentiation between germinoma and other pineal region tumors.
METHOD
This retrospective study consisted of 72 patients with pathologically proven pineal region tumors between January 2010 and August 2020. Tumors were classified as germinomas (40), non-germinomatous germ cell tumors (11) (NGGCT), pineal parenchymal tumors (10) (PPT), and other types of tumors (11). Visual scale score, ADC values and SWI intratumoral susceptibility signal (ITSS) score were analyzed and compared to histopathology data.
RESULTS
The mean apparent diffusion coefficient (ADCmean) and minimum apparent diffusion coefficient (ADCmin) ratio of germinoma were significantly lower than NGGCT. ADCmean or ADCmin cut-off ratio of ≤ 1.48 or ≤ 1.32 allowed for discrimination between germinoma and NGGCT with sensitivity and specificity of 100 % and 63.6 %. An ADCmin cut-off ratio of ≥ 0.93 allowed for discrimination between germinoma and PPT with sensitivity and specificity of 60 % and 80.0 %. ADCmin cut-off ratio of ≤ 1.15 allowed for discrimination of germinoma from other types of tumors with sensitivity and specificity of 87.5 % and 54.5 %.
CONCLUSIONS
ADC ratio can differentiate germinoma from other types of pineal region tumors. Our initial results suggest that ITSS score was not significantly correlated with specific histology subtype.
Topics: Humans; Pinealoma; Retrospective Studies; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging; Germinoma; Neoplasms, Germ Cell and Embryonal; Cell Differentiation; Brain Neoplasms; Pineal Gland
PubMed: 36584565
DOI: 10.1016/j.ejrad.2022.110663 -
Physiological Research Dec 2019The pineal gland (glandula pinealis) is neuroendocrine gland located at the epithalamus of the brain secreting melatonin. The aim of this study was to explore effects of...
The pineal gland (glandula pinealis) is neuroendocrine gland located at the epithalamus of the brain secreting melatonin. The aim of this study was to explore effects of prenatal hypoxia in rats at the age of 33 weeks on the occurrence of pineal gland calcification. Distribution and chemical composition of calcerous material by light, scanning and transmission electron microscopy was investigated. Melatonin concentrations in blood plasma by direct radioimmunoassay were measured. Rats were exposed to prenatal hypoxia for 12 h at day 20 of development and second group to prenatal hypoxia for 2x8 h at days 19 and 20 of development. Vacuoles of intracellular edema in the pineal samples after 12 h hypoxia were found. Their size ranges up to 30 µm. Some of them were filled with the flocculent and fibrous material. Samples of pineal glands after 2 x 8 h hypoxia revealed the pericellular edema of pinealocytes. The amount of calcium rich particles in 2 x 8 h hypoxia group was lower than in 12 h hypoxia group. Plasma melatonin levels did not differ between control and both hypoxia groups. We concluded that calcification is a process induced by osteoblasts and osteocytes with melatonin as a promotor and it is favored under hypoxic conditions.
Topics: Animals; Calcinosis; Hypoxia; Male; Pineal Gland; Rats, Wistar
PubMed: 32118471
DOI: 10.33549/physiolres.934378 -
Micron (Oxford, England : 1993) Feb 2022The histological structure of the avian pineal gland during embryonic life has so far only been studied in chickens. It is known that the pineal organs of hatched...
The histological structure of the avian pineal gland during embryonic life has so far only been studied in chickens. It is known that the pineal organs of hatched chickens and turkeys differ significantly from each other based on their morphology and physiology. The aim of the present study was to investigate the histological structure of the embryonic pineal gland of domestic turkeys. The study was performed on turkey embryos aged 4-28 days. Along with histological analyses, three-dimensional (3D) images of the pineal glands from embryos aged 6-28 days were also obtained. In four-day-old embryos [embryonic day (ED) 4], primary evagination of the pineal gland from the neuroectoderm of the diencephalon was observed. On ED 6, the evagination formed a pineal recess with a thick and folded wall. In the next embryonic stages, the pineal recess was lengthened to the pineal canal, with the lumen opening to the third ventricle. The connection of the pineal lumen with the ventricular lumen was observed in all studied embryos. The first cellular rosettes without the lumen separated from the wall of the pineal recess occurred on ED 6. Several small and round follicles containing their own lumens were visible on ED 8. On ED 10, the pineal parenchyma was composed mainly of small, round follicles. The first oval follicles appeared on ED 12 and branched follicles appeared on ED 16. In some embryos at different stages, follicles formed from secondary evaginations of the diencephalon epithelium were observed. The turkey pineal organ maintained the follicular type of parenchyma without solid cellular aggregates throughout embryonic life. The pineal follicles originated from: 1) rosettes arising from the wall of the pineal canal (from ED 6); 2) an accessory evagination occurring in the neuroectoderm anteriorly and posteriorly to the pineal canal end (from ED 6); 3) direct development in the walls of larger follicles and detaching from them in a manner similar to the budding process (from ED 14); and 4) fusion of smaller follicles into branched ones. The pineal capsule started to develop on ED 6, first as a vascularization and later as a thin mesenchymal outline around the apical part, then at the dorsal and at the end the ventral part of the pineal gland. The pineal stroma was composed of mesenchymal tissue consisting of abundant in cells and blood vessels. The first evagination of the choroid plexus in the diencephalon was observed on ED 8. The attachment of the pineal gland to the dura mater first occurred on ED 16. Finally, the pineal gland of ED 28 embryos consisted of a wide proximal part attached to the dura mater and a narrow distal part that extended into the pineal stalk, which extended to the intercommissural region of the diencephalon. The present study revealed the occurrence of significant morphological differences in the developing embryonic pineal gland of turkeys compared with chickens.
Topics: Animals; Chickens; Pineal Gland; Turkeys
PubMed: 34923408
DOI: 10.1016/j.micron.2021.103196 -
NeuroImage. Clinical 2021Magnetic resonance imaging (MRI) studies reported pineal gland atrophy in schizophrenia patients and individuals at a clinical high risk of developing psychosis,...
BACKGROUND
Magnetic resonance imaging (MRI) studies reported pineal gland atrophy in schizophrenia patients and individuals at a clinical high risk of developing psychosis, implicating abnormalities in melatonin secretion in the pathophysiology of psychosis. However, it currently remains unclear whether the morphology of the pineal gland contributes to symptomatology and sociocognitive functions.
METHODS
This MRI study examined pineal gland volumes and the prevalence of pineal cysts as well as their relationship with clinical characteristics in 57 at risk mental state (ARMS) subjects, 63 patients with schizophrenia, and 61 healthy controls. The Social and Occupational Functioning Assessment Scale (SOFAS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Brief Assessment of Cognition in Schizophrenia (BACS) were used to assess sociocognitive functions, while the Positive and Negative Syndrome Scale was employed to evaluate clinical symptoms in ARMS subjects and schizophrenia patients.
RESULTS
Pineal gland volumes were significantly smaller in the ARMS and schizophrenia groups than in the controls, while no significant differences were observed in the prevalence of pineal cysts. Although BACS, SCoRS, and SOFAS scores were not associated with pineal morphology, patients with pineal cysts in the schizophrenia group exhibited severe positive psychotic symptoms with rather mild negative symptoms.
CONCLUSION
The present results indicate the potential of pineal atrophy as a vulnerability marker in various stages of psychosis and suggest that pineal cysts influence the clinical subtype of schizophrenia.
Topics: Atrophy; Cysts; Humans; Magnetic Resonance Imaging; Pineal Gland; Psychotic Disorders; Schizophrenia
PubMed: 34461434
DOI: 10.1016/j.nicl.2021.102805 -
Journal of Medicine and Life 2014Melatonin is an indoleamine produced by the pineal gland and secreted in a circadian manner. In the past few decades, research over this topic has been enhanced.... (Review)
Review
Melatonin is an indoleamine produced by the pineal gland and secreted in a circadian manner. In the past few decades, research over this topic has been enhanced. Melatonin has many important roles in the human physiology: regulator of the circadian rhythms, sleep inducer, antioxidant, anticarcinogenic. This paper reviews the involvement of melatonin in embryo fetal development. The pineal gland develops completely postpartum, so both the embryo and the fetus are dependent on the maternal melatonin provided transplacentally. Melatonin appears to be involved in the normal outcome of pregnancy beginning with the oocyte quality and finishing with the parturition. Its pregnancy night-time concentrations increase after 24 weeks of gestation, with significantly high levels after 32 weeks. Melatonin receptors are widespread in the embryo and fetus since early stages. There is solid evidence that melatonin is neuroprotective and has a positive effect on the outcome of the compromised pregnancies. In addition, chronodisruption leads to a reproductive dysfunction. Thus, the influence of melatonin on the developing human fetus may not be limited to the entertaining of circadian rhythmicity, but further studies are needed.
Topics: Embryo, Mammalian; Female; Fertilization in Vitro; Fetal Development; Humans; Melatonin; Pineal Gland; Pregnancy; Receptors, Melatonin
PubMed: 25713608
DOI: No ID Found -
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