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Science (New York, N.Y.) Jul 2023Disruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet the underlying mechanism has remained enigmatic....
Disruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet the underlying mechanism has remained enigmatic. Immunostaining of sympathetic axons in optically cleared pineal glands from humans and mice with cardiac disease revealed their substantial denervation compared with controls. Spatial, single-cell, nuclear, and bulk RNA sequencing traced this defect back to the superior cervical ganglia (SCG), which responded to cardiac disease with accumulation of inflammatory macrophages, fibrosis, and the selective loss of pineal gland-innervating neurons. Depletion of macrophages in the SCG prevented disease-associated denervation of the pineal gland and restored physiological melatonin secretion. Our data identify the mechanism by which diurnal rhythmicity in cardiac disease is disturbed and suggest a target for therapeutic intervention.
Topics: Animals; Humans; Mice; Circadian Rhythm; Heart Diseases; Melatonin; Pineal Gland; Sleep; Sleep Disorders, Circadian Rhythm; Superior Cervical Ganglion; Macrophages; Fibrosis
PubMed: 37471539
DOI: 10.1126/science.abn6366 -
The International Journal of... May 2020The pineal gland, an endocrine organ of the posterior cranial fossa famously involved in sleep and wakefulness, has continually been a topic of scientific advancement... (Review)
Review
The pineal gland, an endocrine organ of the posterior cranial fossa famously involved in sleep and wakefulness, has continually been a topic of scientific advancement and curiosity. We review present an up-to-date review including the anatomy, embryology, and physiology of the pineal gland and its ability to secrete hormones including melatonin, pathophysiology of pineal gland tumors, cysts, and calcifications, their clinical presentation including their association with parkinsonism and precocious puberty, and various treatment approaches. Exploring the biochemistry of melatonin, various calcification morphologies, and pineal tumors may uncover a wider role and the exhaustive case study consolidation allows clinicians to carefully review the literature and aid their treatment approaches. It is imperative that clinicians and diagnosticians are able to distinguish manifestations of an overlooked gland.
Topics: Calcinosis; Humans; Melatonin; Pineal Gland; Pinealoma; Puberty, Precocious
PubMed: 31714865
DOI: 10.1080/00207454.2019.1692838 -
Methods in Molecular Biology (Clifton,... 2022Pineal microdialysis is characterized by the real-time monitoring of melatonin, neurotransmitters, metabolites, and other compounds released by the pineal gland...
Pineal microdialysis is characterized by the real-time monitoring of melatonin, neurotransmitters, metabolites, and other compounds released by the pineal gland throughout 24 h. It is a technique with great advantages that allows in vivo study of the ongoing pineal gland metabolism. In this chapter, we describe the entire process of pineal microdialysis that includes probe manufacturing, surgical procedure for its implantation, and the sample collection process.
Topics: Circadian Rhythm; Melatonin; Microdialysis; Pineal Gland
PubMed: 36180678
DOI: 10.1007/978-1-0716-2593-4_9 -
Cellular and Molecular Neurobiology Aug 2023Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin... (Review)
Review
Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin production and to lesser extent by retina, lymphocytes, bone marrow, gastrointestinal tract, and thymus. Melatonin as a neurohormone is released into circulation wherein it penetrates all tissues of the body. Melatonin synthesis and secretion is supressed by light and enhanced by dark. Melatonin mostly exerts its effect through different pathways with melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) being the predominant type of receptor that are mainly expressed by many mammalian organs. Melatonin helps to regulate sleep patterns and circadian rhythms. In addition, melatonin acts as an antioxidant and scavenges excessive free radicals generated in the body by anti-excitatory and anti-inflammatory properties. A multiple array of other functions are displayed by melatonin that include oncostatic, hypnotic, immune regulation, reproduction, puberty timing, mood disorders, and transplantation. Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there. In the past century, a growing interest has been developed regarding the wide use of melatonin in treating various diseases like inflammatory, gastrointestinal, cancer, mood disorders, and others. Several melatonin agonists have been synthesized and are widely used in disease treatment. In this review, an effort has been made to describe the biochemistry of melatonin along with its therapeutic potential in various diseases of humans.
Topics: Animals; Humans; Melatonin; Receptors, Melatonin; Antioxidants; Circadian Rhythm; Pineal Gland; Mammals
PubMed: 36752886
DOI: 10.1007/s10571-023-01324-w -
Frontiers in Endocrinology 2020
Topics: Animals; Circadian Rhythm; Health Status; Humans; Melatonin; Metabolic Diseases; Pineal Gland
PubMed: 33324351
DOI: 10.3389/fendo.2020.613549 -
Methods in Molecular Biology (Clifton,... 2022Pineal gland secretes the hormone melatonin at night with a circadian rhythm. The synthesis and secretion of melatonin are stimulated at night by norepinephrine released...
Pineal gland secretes the hormone melatonin at night with a circadian rhythm. The synthesis and secretion of melatonin are stimulated at night by norepinephrine released by sympathetic postganglionic neurons projecting from the superior cervical ganglia. Norepinephrine simultaneously activates α- and β-adrenoceptors, triggering melatonin synthesis.To study the regulation of melatonin production and secretion, it is very convenient to use an ex vivo preparation. Thus, it is possible to keep intact pineal glands in culture and to study the actions of agonists, antagonists, modulators, toxic agents, etc., in melatonin synthesis. Artificial melatonin synthesis stimulation in vitro is usually achieved by using a β-adrenergic agonist alone or in association with an α-adrenergic agonist. In this chapter, the methodology of cultured pineal glands will be described. Several papers were published by our group using this methodology, approaching the role played in melatonin synthesis control by angiotensin II and IV, insulin, glutamate, voltage-gated calcium channels, anhydroecgonine methyl ester (AEME, crack-cocaine product), monosodium glutamate (MSG), signaling pathways like NFkB, pathophysiological conditions like diabetes, etc.
Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Angiotensin II; Calcium Channels; Circadian Rhythm; Cocaine; Insulins; Melatonin; Norepinephrine; Pineal Gland; Receptors, Adrenergic, beta; Sodium Glutamate
PubMed: 36180681
DOI: 10.1007/978-1-0716-2593-4_12 -
Methods in Molecular Biology (Clifton,... 2022The pinealectomy technique consists of the surgical removal of the superficial pineal gland. This procedure allows the ablation of circulating indoles produced by this...
The pinealectomy technique consists of the surgical removal of the superficial pineal gland. This procedure allows the ablation of circulating indoles produced by this gland. Withdrawal of systemic melatonin, a pineal hormone, affects animal circadian rhythms and induces several physiological changes that are the subject of many investigations. In this chapter, we describe the pinealectomy protocol adapted to rats. We describe the animal placement on the stereotaxic fixation system, and the procedure for the pineal gland removal and animal recovery from surgery.
Topics: Animals; Circadian Rhythm; Melatonin; Pineal Gland; Pinealectomy; Rats
PubMed: 36180676
DOI: 10.1007/978-1-0716-2593-4_7 -
Advances in Experimental Medicine and... 2020A wide and heterogeneous variety of tumors develop from the pineal gland. Pineal parenchymal tumors, germ cell tumors, and glial tumors represent most of them. The... (Review)
Review
A wide and heterogeneous variety of tumors develop from the pineal gland. Pineal parenchymal tumors, germ cell tumors, and glial tumors represent most of them. The molecular profiles and tumor microenvironment play a key role in the development and progression of pineal gland tumors. Consequently, they represent important factors that may determine the efficacy of the different treatment modalities and the clinical outcome. Current literature is scarce regarding the microenvironment research of pineal gland tumors. Here, we review the cellular and molecular profile of the pineal gland tumor microenvironment.
Topics: Brain Neoplasms; Glioma; Humans; Pineal Gland; Pinealoma; Tumor Microenvironment
PubMed: 34185290
DOI: 10.1007/978-3-030-59038-3_8 -
Science (New York, N.Y.) Jul 2023Cardiac dysfunction triggers immune-mediated loss of pineal gland melatonin release.
Cardiac dysfunction triggers immune-mediated loss of pineal gland melatonin release.
Topics: Humans; Heart Failure; Melatonin; Pineal Gland; Sleep Disorders, Circadian Rhythm
PubMed: 37471547
DOI: 10.1126/science.adj0217 -
Molecules (Basel, Switzerland) Nov 2022Melatonin, -acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly... (Review)
Review
Melatonin, -acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina's exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature. Furthermore, melatonin has pleiotropic actions, which affect, for instance, the modulation of the immune and the cardiovascular systems, as well as the neuroprotection achieved by scavenging free radicals. Recent research has supported that melatonin contributes to neuronal survival, proliferation, and differentiation, such as dendritogenesis and axogenesis, and its processes are similar to those caused by Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5. Furthermore, this indolamine has apoptotic and anti-inflammatory actions in specific brain regions akin to those exerted by neurotrophic factors. This review presents evidence suggesting melatonin's role as a neurotrophic factor, describes the signaling pathways involved in these processes, and, lastly, highlights the therapeutic implications involved.
Topics: Melatonin; Pineal Gland; Nerve Growth Factors; Suprachiasmatic Nucleus; Sleep; Transforming Growth Factor beta
PubMed: 36431847
DOI: 10.3390/molecules27227742