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ASN Neuro 2022The circumventricular organs (CVOs) are unique areas within the central nervous system. They serve as a portal for the rest of the body and, as such, lack a blood-brain... (Review)
Review
The circumventricular organs (CVOs) are unique areas within the central nervous system. They serve as a portal for the rest of the body and, as such, lack a blood-brain barrier. Microglia are the primary resident immune cells of the brain parenchyma. Within the CVOs, microglial cells find themselves continuously challenged and stimulated by local and systemic stimuli, even under steady-state conditions. Therefore, CVO microglia in their typical state often resemble the activated microglial forms found elsewhere in the brain as they are responding to pathological conditions or other stressors. In this review, I focus on the dynamics of CVO microglia, using the pineal gland as a specific CVO example. Data related to microglia heterogeneity in both homeostatic and unhealthy environments are presented and discussed, including those recently generated by using advanced single-cell and single-nucleus technology. Finally, perspectives in the CVO microglia field are also included.Microglia in circumventricular organs (CVOs) continuously adapt to react differentially to the diverse challenges they face. Herein, I discuss microglia heterogeneity in CVOs, including pineal gland. Further studies are needed to better understand microglia dynamics in these unique brain areas. .
Topics: Microglia; Pineal Gland; Circumventricular Organs; Blood-Brain Barrier; Brain
PubMed: 36317305
DOI: 10.1177/17590914221135697 -
Biochimie Apr 2024Melatonin is a pleiotropic neurohormone found in different animal, plant, and microorganism species. It is a product resulting from tryptophan metabolism in the pineal... (Review)
Review
Melatonin is a pleiotropic neurohormone found in different animal, plant, and microorganism species. It is a product resulting from tryptophan metabolism in the pineal gland and is widely known for its ability to synchronize the circadian rhythm to antitumor functions in different types of cancers. The molecular mechanisms responsible for its immunomodulatory, antioxidant and cytoprotective effects involve binding to high-affinity G protein-coupled receptors and interactions with intracellular targets that modulate signal transduction pathways. In vitro and in vivo studies have reported the therapeutic potential of melatonin in different infectious and parasitic diseases. In this review, the protective and pathophysiological roles of melatonin in fighting protozoan and helminth infections and the possible mechanisms involved against these stressors will be discussed.
Topics: Animals; Melatonin; Pineal Gland; Antioxidants; Parasitic Diseases; Helminths; Circadian Rhythm
PubMed: 37541568
DOI: 10.1016/j.biochi.2023.07.021 -
Molecules (Basel, Switzerland) Jun 2021The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter,... (Review)
Review
The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter, focused, and fine-tuned therapy, enhancing the therapeutic efficacy of chemical agents at the molecular level while reducing their toxic effects. Melatonin (-acetyl-5-methoxytriptamine) is a small indoleamine secreted essentially by the pineal gland during darkness, but also produced by most cells in a non-circadian manner from which it is not released into the blood. Although the therapeutic promise of melatonin is indisputable, aspects regarding optimal dosage, biotransformation and metabolism, route and time of administration, and targeted therapy remain to be examined for proper treatment results. Recently, prolonged release of melatonin has shown greater efficacy and safety when combined with a nanostructured formulation. This review summarizes the role of melatonin incorporated into different nanocarriers (e.g., lipid-based vesicles, polymeric vesicles, non-ionic surfactant-based vesicles, charge carriers in graphene, electro spun nanofibers, silica-based carriers, metallic and non-metallic nanocomposites) as drug delivery system platforms or multilevel determinations in various in vivo and in vitro experimental conditions. Melatonin incorporated into nanosized materials exhibits superior effectiveness in multiple diseases and pathological processes than does free melatonin; thus, such information has functional significance for clinical intervention.
Topics: Animals; Circadian Rhythm; Drug Carriers; Drug Delivery Systems; Humans; Melatonin; Nanoparticles; Nanostructures; Pineal Gland
PubMed: 34200947
DOI: 10.3390/molecules26123562 -
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 -
General and Comparative Endocrinology Jan 2021Pregnancy and lactation are reproductive processes that rely on physiological adaptations that should be timely and adequately triggered to guarantee both maternal and... (Review)
Review
Pregnancy and lactation are reproductive processes that rely on physiological adaptations that should be timely and adequately triggered to guarantee both maternal and fetal health. Pineal melatonin is a hormone that presents daily and seasonal variations that synchronizes the organism's physiology to the different demands across time through its specific mechanisms and ways of action. The reproductive system is a notable target for melatonin as it actively participates on reproductive physiology and regulates the hypothalamus-pituitary-gonads axis, influencing gonadotropins and sexual hormones synthesis and release. For its antioxidant properties, melatonin is also vital for the oocytes and spermatozoa quality and viability, and for blastocyst development. Maternal pineal melatonin blood levels increase during pregnancy and triggers the maternal physiological alterations in energy metabolism both during pregnancy and lactation to cope with the energy demands of both periods and to promote adequate mammary gland development. Moreover, maternal melatonin freely crosses the placenta and is the only source of this hormone to the fetus. It importantly times the conceptus physiology and influences its development and programing of several functions that depend on neural and brain development, ultimately priming adult behavior and energy and glucose metabolism. The present review aims to explain the above listed melatonin functions, including the potential alterations observed in the progeny gestated under maternal chronodisruption and/or hypomelatoninemia.
Topics: Animals; Female; Fetal Development; Humans; Lactation; Mammary Glands, Human; Melatonin; Nervous System; Pineal Gland; Pregnancy
PubMed: 33031801
DOI: 10.1016/j.ygcen.2020.113633 -
Seminars in Cell & Developmental Biology Nov 2019The pineal gland (PG) derives from the neural tube, like the rest of the central nervous system (CNS). The PG is specialized in synthesizing and secreting melatonin in a... (Review)
Review
The pineal gland (PG) derives from the neural tube, like the rest of the central nervous system (CNS). The PG is specialized in synthesizing and secreting melatonin in a circadian fashion. The nocturnal elevation of melatonin is a highly conserved feature among species which proves its importance in nature. Here, we review a limited set of intrinsic and extrinsic regulatory elements that have been shown or proposed to influence the PG's melatonin production, as well as pineal ontogeny and homeostasis. Intrinsic regulators include the transcription factors CREB, Pax6 and NeuroD1. In addition, microglia within the PG participate as extrinsic regulators of these functions. We further discuss how these same elements work in other parts of the CNS, and note similarities and differences to their roles in the PG. Since the PG is a relatively well-defined and highly specialized organ within the CNS, we suggest that applying this comparative approach to additional PG regulators may be a useful tool for understanding complex areas of the brain, as well as the influence of the PG in both health and disease, including circadian functions and disorders.
Topics: Animals; Humans; Microglia; Phenotype; Pineal Gland; Signal Transduction; Transcription Factors; Transcription, Genetic
PubMed: 30502386
DOI: 10.1016/j.semcdb.2018.11.004 -
Journal of Pineal Research Sep 2023Circadian clock gene expression in the suprachiasmatic nucleus (SCN) controls 24 h rhythms in body functions, but clock genes are also expressed in extra-hypothalamic...
Circadian clock gene expression in the suprachiasmatic nucleus (SCN) controls 24 h rhythms in body functions, but clock genes are also expressed in extra-hypothalamic tissues, including the melatonin-producing pineal gland. The nocturnal increase in pineal melatonin synthesis is a hallmark in circadian biology, but the role of local clock gene oscillations in the mammalian pineal gland is unknown. The aim of this work is to determine the role of clock genes in endocrine function of the pineal gland with focus on the Aanat transcript encoding the rhythm-generating enzyme of melatonin synthesis. Using the rat as a model, we here established 24 h expression patterns of clock genes in the pineal gland in vivo. Lesion studies showed that rhythmic clock gene expression in the pineal gland to a large extent depends on the SCN; further, clock gene rhythms could be re-established in cultured pineal cells synchronized by rhythmic stimulation with norepinephrine in 12 h pulses, suggesting that pineal cells house a slave oscillator controlled by adrenergic signaling in the gland. Histological analyses showed that clock genes are expressed in pinealocytes and colocalize with Aanat transcripts, thus potentially enabling clock gene products to control cellular melatonin production. To test this, cultured pineal cells were transfected using small interfering RNA to knock down clock gene expression. While successful knockdown of Per1 had a minor effect on Aanat, Clock knockdown produced a marked overexpression of Aanat in the pinealocytes. Our study suggests that SCN-dependent rhythmic Clock gene expression in the pinealocytes regulates the daily profile of Aanat expression.
Topics: Rats; Animals; Melatonin; Pineal Gland; Transcription Factors; Circadian Clocks; Suprachiasmatic Nucleus; Circadian Rhythm; Mammals
PubMed: 37349875
DOI: 10.1111/jpi.12893 -
The Prostate Jun 2021Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6-sulfatoxymelatonin have been associated with increased risk...
INTRODUCTION
Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6-sulfatoxymelatonin have been associated with increased risk of advanced prostate cancer, but the relationship between pineal gland volume and composition and prostate cancer risk has not been examined.
MATERIALS AND METHODS
We utilized data from 864 men from the AGES-Reykjavik Study with complete pineal gland volumes and urinary 6-sulfatoxymelatonin measurements. Pineal parenchyma, calcification, and cyst volumes were calculated from brain magnetic resonance imaging. Levels of 6-sulfatoxymelatonin were assayed from prediagnostic urine samples. We calculated Pearson correlation coefficients between parenchyma volume and urinary 6-sulfatoxymelatonin levels. We used Cox proportional hazards regression to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) comparing prostate cancer risk across parenchyma volume tertiles and across categories factoring in parenchyma volume, gland composition, and urinary 6-sulfatoxymelatonin level.
RESULTS
Parenchyma volume was moderately correlated with urinary 6-sulfatoxymelatonin level (r = .24; p < .01). There was no statistically significant association between parenchyma volume tertile and prostate cancer risk. Men with high parenchyma volume, pineal cysts and calcifications, and low urinary 6-sulfatoxymelatonin levels had almost twice the risk of total prostate cancer as men with low parenchyma volume, no pineal calcifications or cysts, and low urinary 6-sulfatoxymelatonin levels (HR: 1.98; 95% CI: 1.02, 3.84; p: .04).
CONCLUSIONS
Although parenchyma volume is not associated with prostate cancer risk, pineal gland composition and other circadian dynamics may influence risk for prostate cancer. Additional studies are needed to examine the interplay of pineal gland volume, composition, and melatonin levels on prostate cancer risk.
Topics: Aged; Aged, 80 and over; Humans; Iceland; Magnetic Resonance Imaging; Male; Melatonin; Organ Size; Pineal Gland; Prostatic Neoplasms; Registries; Risk
PubMed: 33860950
DOI: 10.1002/pros.24130 -
Child's Nervous System : ChNS :... Jan 2022Pineal, sellar and suprasellar tumours in children comprise a wide range of diseases with different biological behaviours and clinical management. Neuroimaging plays a... (Review)
Review
INTRODUCTION
Pineal, sellar and suprasellar tumours in children comprise a wide range of diseases with different biological behaviours and clinical management. Neuroimaging plays a critical role in the diagnosis, treatment planning and follow up of these patients, but imaging interpretation can prove challenging due to the significant overlap in radiological features.
MATERIALS AND METHOD
A review of the literature was performed by undertaking a search of the MEDLINE and EMBASE databases for appropriate MeSH terminology. Identified abstracts were screened for inclusion and articles meeting the objectives of the review were included.
RESULTS AND CONCLUSION
In this article, we review radiological appearances of common and uncommon pineal, sellar and suprasellar tumours occurring in the paediatric population. We discuss the importance of anatomical localization, clinical information and cerebrospinal fluid tumour markers, and propose a practical approach to differential diagnosis. Lastly, we discuss future directions and prospective new imaging strategies to support state-of-the-art patient care.
Topics: Child; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Neoplasms; Neuroimaging; Pineal Gland; Prospective Studies
PubMed: 34529090
DOI: 10.1007/s00381-021-05359-6 -
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