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Molecules (Basel, Switzerland) Jan 2018The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective... (Review)
Review
The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin's synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.
Topics: Aging; Animals; Calcinosis; Humans; Melatonin; Pineal Gland; Rejuvenation
PubMed: 29385085
DOI: 10.3390/molecules23020301 -
Frontiers in Endocrinology 2020
Topics: Animals; Circadian Rhythm; Health Status; Humans; Melatonin; Metabolic Diseases; Pineal Gland
PubMed: 33324351
DOI: 10.3389/fendo.2020.613549 -
The Journal of Clinical Pediatric... 2018Fluoride, one of the most celebrated ingredients for the prevention of dental caries in the 20th century, has also been controversial for its use in dentifrices and... (Review)
Review
Fluoride, one of the most celebrated ingredients for the prevention of dental caries in the 20th century, has also been controversial for its use in dentifrices and other applications. In the current review, we have concentrated primarily on early-life exposure to fluoride and how it may affect the various organs. The most recent controversial aspects of fluoride are related to toxicity of the developing brain and how it may possibly result in the decrease of intelligence quotient (IQ), autism, and calcification of the pineal gland. In addition, it has been reported to have possible effects on bone and thyroid glands. If nutritional stress is applied during a critical period of growth and development, the organ(s) and/or body will never recover once they pass through the critical period. For example, if animals are force-fed during experiments, they will simply get fat but never reach the normal size. Although early-life fluoride exposure causing fluorosis is well reported in the literature, the dental profession considers it primarily as an esthetic rather than a serious systemic problem. In the current review, we wanted to raise the possibility of future disease as a result of early-life exposure to fluoride. It is not currently known how fluoride will become a cause of future disease. Studies of other nutritional factors have shown that the effects of early nutritional stress are a cause of disease in later life.
Topics: Autistic Disorder; Bone Neoplasms; Brain; Calcinosis; Cariostatic Agents; Fluoridation; Fluorides; Humans; Intelligence Tests; Osteosarcoma; Pineal Gland; Thyroid Hormones
PubMed: 29763350
DOI: 10.17796/1053-4625-42.5.1 -
Frontiers in Endocrinology 2020Similar to the adrenal glands, gonads, and placenta, vertebrate brains also produce various steroids, which are known as "neurosteroids." Neurosteroids are mainly... (Review)
Review
Similar to the adrenal glands, gonads, and placenta, vertebrate brains also produce various steroids, which are known as "neurosteroids." Neurosteroids are mainly synthesized in the hippocampus, hypothalamus, and cerebellum; however, it has recently been discovered that in birds, the pineal gland, a photosensitive region in the brain, produces more neurosteroids than other brain regions. A series of experiments using molecular and biochemical techniques have found that the pineal gland produces various neurosteroids, including sex steroids, from cholesterol. For instance, allopregnanolone and 7α-hydroxypregnenolone are actively produced in the pineal gland, unlike in other brain regions. Pineal 7α-hydroxypregnenolone, an up-regulator of locomotion, enhances locomotor activity in response to light stimuli in birds. Additionally, pineal allopregnanolone acts on Purkinje cells in the cerebellum and prevents neuronal apoptosis within the developing cerebellum in juvenile birds. Furthermore, exposure to light during nighttime hours can cause loss of diurnal variations of pineal allopregnanolone synthesis during early posthatch life, eventually leading to cerebellar Purkinje cell death in juvenile birds. In light of these new findings, this review summarizes the biosynthesis and physiological functions of pineal neurosteroids. Given that the circadian rhythms of individuals in modern societies are constantly interrupted by artificial light exposure, these findings in birds, which are excellent model diurnal animals, may have direct implications for addressing problems regarding the mental health and brain development of humans.
Topics: Animals; Cell Physiological Phenomena; Humans; Motor Activity; Neurosteroids; Pineal Gland
PubMed: 32849313
DOI: 10.3389/fendo.2020.00549 -
International Journal of Molecular... Nov 2020For years the thymus gland (TG) and the pineal gland (PG) have been subject of increasingly in-depth studies, but only recently a link that can associate the activities... (Review)
Review
For years the thymus gland (TG) and the pineal gland (PG) have been subject of increasingly in-depth studies, but only recently a link that can associate the activities of the two organs has been identified. Considering, on the one hand, the well-known immune activity of thymus and, on the other, the increasingly emerging immunological roles of circadian oscillators and the rhythmically secreted main pineal product, melatonin, many studies aimed to analyse the possible existence of an interaction between these two systems. Moreover, data confirmed that the immune system is functionally associated with the nervous and endocrine systems determining an integrated dynamic network. In addition, recent researches showed a similar, characteristic involution process both in TG and PG. Since the second half of the 20th century, evidence led to the definition of an effectively interacting thymus-pineal axis (TG-PG axis), but much has to be done. In this sense, the aim of this review is to summarize what is actually known about this topic, focusing on the impact of the TG-PG axis on human life and ageing. We would like to give more emphasis to the implications of this dynamical interaction in a possible therapeutic strategy for human health. Moreover, we focused on all the products of TG and PG in order to collect what is known about the role of peptides other than melatonin. The results available today are often unclear and not linear. These peptides have not been well studied and defined over the years. In this review we hope to awake the interest of the scientific community in them and in their future pharmacological applications.
Topics: Aging; Animals; Circadian Rhythm; Humans; Melatonin; Peptides; Pineal Gland; Thymus Gland
PubMed: 33233845
DOI: 10.3390/ijms21228806 -
International Journal of Molecular... Nov 2021Melatonin is a highly conserved molecule found in prokaryotes and eukaryotes that acts as the darkness hormone, translating environmental lighting to the whole body, and... (Review)
Review
Melatonin is a highly conserved molecule found in prokaryotes and eukaryotes that acts as the darkness hormone, translating environmental lighting to the whole body, and as a moderator of innate and acquired defense, migration, and cell proliferation processes. This review evaluates the importance of pineal activity in monitoring PAMPs and DAMPs and in mounting an inflammatory response or innate immune response. Activation of the immune-pineal axis, which coordinates the pro-and anti-inflammatory phases of an innate immune response, is described. PAMPs and DAMPs promote the immediate suppression of melatonin production by the pineal gland, which allows leukocyte migration. Monocyte-derived macrophages, important phagocytes of microbes, and cellular debris produce melatonin locally and thereby initiate the anti-inflammatory phase of the acute inflammatory response. The role of locally produced melatonin in organs that directly contact the external environment, such as the skin and the gastrointestinal and respiratory tracts, is also discussed. In this context, as resident macrophages are self-renewing cells, we explore evidence indicating that, besides avoiding overreaction of the immune system, extra-pineal melatonin has a fundamental role in the homeostasis of organs and tissues.
Topics: Animals; Humans; Immunity, Innate; Inflammation; Macrophages; Melatonin; Pineal Gland
PubMed: 34830026
DOI: 10.3390/ijms222212143 -
Cell Transplantation 2016Melatonin (N-acetyl-5-methoxytryptamine) is a hormone derived from the pineal gland that has a wide range of clinical applications. While melatonin was originally... (Review)
Review
Melatonin (N-acetyl-5-methoxytryptamine) is a hormone derived from the pineal gland that has a wide range of clinical applications. While melatonin was originally assessed as a hormone specializing in regulation of the normal circadian rhythm in mammals, it now has been shown to be an effective free radical scavenger and antioxidant. Current research has focused on central nervous system (CNS) disorders, stroke in particular, for potential melatonin-based therapeutics. As of now, the realm of potential therapy regimens is focused on three main treatments: exogenously delivered melatonin, pineal gland grafting, and melatonin-mediated stem cell therapy. All therapies contain both costs and benefits, and current research is still focused on finding the best treatment plan. While comprehensive research has been conducted, more research regarding the safety of such therapies is needed in order to transition into the clinical level of testing. Antioxidants such as traditional Chinese medicine, (-)-epigallocatechin-3-gallate (EGCG), and lavender oil, which have been used for thousands of years as treatment, are now gaining recognition as effective melatonin treatment alternatives. This review will further discuss relevant studies assessing melatonin-based therapeutics and provide evidence of other natural melatonin treatment alternatives for the treatment of stroke.
Topics: Animals; Antioxidants; Catechin; Cell- and Tissue-Based Therapy; Humans; Melatonin; Neuroprotection; Neuroprotective Agents; Pineal Gland; Receptors, Melatonin; Stem Cell Transplantation; Stem Cells; Stroke
PubMed: 26497887
DOI: 10.3727/096368915X689749 -
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 -
Journal of Pineal Research Mar 2021Our daily rhythmicity is controlled by a circadian clock with a specific set of genes located in the suprachiasmatic nucleus in the hypothalamus. Mast cells (MCs) are... (Review)
Review
Our daily rhythmicity is controlled by a circadian clock with a specific set of genes located in the suprachiasmatic nucleus in the hypothalamus. Mast cells (MCs) are major effector cells that play a protective role against pathogens and inflammation. MC distribution and activation are associated with the circadian rhythm via two major pathways, IgE/FcεRI- and IL-33/ST2-mediated signaling. Furthermore, there is a robust oscillation between clock genes and MC-specific genes. Melatonin is a hormone derived from the amino acid tryptophan and is produced primarily in the pineal gland near the center of the brain, and histamine is a biologically active amine synthesized from the decarboxylation of the amino acid histidine by the L-histidine decarboxylase enzyme. Melatonin and histamine are previously reported to modulate circadian rhythms by pathways incorporating various modulators in which the nuclear factor-binding near the κ light-chain gene in B cells, NF-κB, is the common key factor. NF-κB interacts with the core clock genes and disrupts the production of pro-inflammatory cytokine mediators such as IL-6, IL-13, and TNF-α. Currently, there has been no study evaluating the interdependence between melatonin and histamine with respect to circadian oscillations in MCs. Accumulating evidence suggests that restoring circadian rhythms in MCs by targeting melatonin and histamine via NF-κB may be promising therapeutic strategy for MC-mediated inflammatory diseases. This review summarizes recent findings for circadian-mediated MC functional roles and activation paradigms, as well as the therapeutic potentials of targeting circadian-mediated melatonin and histamine signaling in MC-dependent inflammatory diseases.
Topics: Animals; Circadian Rhythm; Histamine; Histidine Decarboxylase; Humans; Interleukin-13; Interleukin-6; Mast Cells; Melatonin; Pineal Gland; Tumor Necrosis Factor-alpha
PubMed: 33020940
DOI: 10.1111/jpi.12699 -
Journal of Anatomy Apr 2018The circumventricular organs (CVOs) are specialised neuroepithelial structures found in the midline of the brain, grouped around the third and fourth ventricles. They... (Review)
Review
The circumventricular organs (CVOs) are specialised neuroepithelial structures found in the midline of the brain, grouped around the third and fourth ventricles. They mediate the communication between the brain and the periphery by performing sensory and secretory roles, facilitated by increased vascularisation and the absence of a blood-brain barrier. Surprisingly little is known about the origins of the CVOs (both developmental and evolutionary), but their functional and organisational similarities raise the question of the extent of their relationship. Here, I review our current knowledge of the embryonic development of the seven major CVOs (area postrema, median eminence, neurohypophysis, organum vasculosum of the lamina terminalis, pineal organ, subcommissural organ, subfornical organ) in embryos of different vertebrate species. Although there are conspicuous similarities between subsets of CVOs, no unifying feature characteristic of their development has been identified. Cross-species comparisons suggest that CVOs also display a high degree of evolutionary flexibility. Thus, the term 'CVO' is merely a functional definition, and features shared by multiple CVOs may be the result of homoplasy rather than ontogenetic or phylogenetic relationships.
Topics: Animals; Area Postrema; Blood-Brain Barrier; Circumventricular Organs; Humans; Hypothalamus; Phylogeny; Pineal Gland; Pituitary Gland, Posterior; Subcommissural Organ; Subfornical Organ
PubMed: 29280147
DOI: 10.1111/joa.12771