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Integrative and Comparative Biology Apr 2024Melatonin is a hormone known as an endogenous temporal marker signaling the dark phase of the day. Although the eyes seem to be the main site of melatonin production in...
Melatonin is a hormone known as an endogenous temporal marker signaling the dark phase of the day. Although the eyes seem to be the main site of melatonin production in amphibians, little information is available about the natural variation in the ocular melatonin levels and its modulation following immune stimulation. We investigated the daily variation of plasma and ocular melatonin levels in bullfrogs (Lithobates catesbeianus) and their modulation following an immune stimulation with lipopolysaccharide (LPS) in yellow cururu toads (Rhinella icterica). For the daily variation, bullfrogs were bled and then euthanized for eye collection every 3h over 24h to determine plasma and ocular melatonin levels. We found a positive correlation between ocular and plasma melatonin levels, with maximum values at night (22h) for both plasma and the eyes. For immune stimulation, yellow cururu toads received an intraperitoneal injection of LPS or saline solution during the day (10h) or at night (22h). Two hours after injection, toads were bled and euthanized for eye collection to obtain plasma and ocular melatonin levels. In addition, the liver and bone marrow were collected to investigate local melatonin modulation. Our results demonstrate that retina light-controlled rhythmic melatonin production is suppressed while liver and bone marrow melatonin levels increase during the inflammatory assemblage in anurans. Interestingly, the LPS injection decreased only ocular melatonin levels, reinforcing the central role of the eyes (i.e., retina) as an essential organ of melatonin production, and a similar role to the pineal gland during the inflammatory response in amphibians. Together, these results point to a possible immune-pineal-ocular axis in amphibians, yet to be fully described in this group.
PubMed: 38658196
DOI: 10.1093/icb/icae026 -
International Journal of Molecular... Apr 2024Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before...
Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before reactivation, which is associated with symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, the development of new antiviral agents is sought due to the presence of resistant viruses. Melatonin, a molecule secreted by the pineal gland, has been shown to be an antioxidant, inducer of antioxidant enzymes, and regulator of various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. This study focuses on melatonin's role in HSV-1 replication and the underlying mechanisms. Melatonin was found to decrease the synthesis of HSV-1 proteins in infected Vero cells measured by immunofluorescence, indicating an inhibition of HSV-1 replication. Additionally, it regulates the activities of antioxidant enzymes and affects proteasome activity. Melatonin activates the unfolded protein response (UPR) and autophagy and suppresses apoptosis in HSV-1-infected cells. In summary, melatonin demonstrates an inhibitory role in HSV-1 replication by modulating various cellular responses, suggesting its potential utility in the treatment of viral infections.
Topics: Chlorocebus aethiops; Animals; Melatonin; Antioxidants; Herpesvirus 1, Human; Vero Cells; Pineal Gland
PubMed: 38612846
DOI: 10.3390/ijms25074037 -
Frontiers in Microbiology 2024Melatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model...
INTRODUCTION
Melatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model to investigate the functions of pineal MEL and its relationship with various diseases. However, the effect of PINX on the gastrointestinal tract (GIT) MEL levels and gut microbiome in pigs has not been previously reported.
METHODS
By using a newly established pig PINX model, we detected the levels of MEL in the GIT by liquid chromatography-tandem mass spectrometry. In addition, we examined the effects of PINX on the expression of MEL synthesis enzymes, intestinal histomorphology, and the intestinal barrier. Furthermore, 16S rRNA sequencing was performed to analyze the colonic microbiome.
RESULTS
PINX reduced serum MEL levels but did not affect GIT MEL levels. Conversely, MEL supplementation increased MEL levels in the GIT and intestinal contents. Neither PINX nor MEL supplementation had any effect on weight gain, organ coefficient, serum biochemical indexes, or MEL synthetase arylalkylamine N-acetyltransferase (AANAT) expression in the duodenum, ileum, and colon. Furthermore, no significant differences were observed in the intestinal morphology or intestinal mucosal barrier function due to the treatments. Additionally, 16S rRNA sequencing revealed that PINX had no significant impact on the composition of the intestinal microbiota. Nevertheless, MEL supplementation decreased the abundance of Fibrobacterota and increased the abundance of Actinobacteriota, Desulfobacterota, and Chloroflexi.
CONCLUSION
We demonstrated that synthesis of MEL in the GIT is independent of the pineal gland. PINX had no influence on intestinal MEL level and microbiota composition in pigs, while exogenous MEL alters the structure of the gut microbiota.
PubMed: 38596375
DOI: 10.3389/fmicb.2024.1352586 -
Journal of Clinical Medicine Feb 2024Pineal parenchymal cell tumors constitute a rare group of primary central nervous system neoplasms (less than 1%). Their classification, especially the intermediate... (Review)
Review
BACKGROUND
Pineal parenchymal cell tumors constitute a rare group of primary central nervous system neoplasms (less than 1%). Their classification, especially the intermediate subtype (PPTIDs), remains challenging.
METHODS
A literature review was conducted, navigating through anatomo-pathological, radiotherapy, and neurosurgical dimensions, aiming for a holistic understanding of these tumors.
RESULTS
PPTIDs, occupying an intermediate spectrum of malignancy, reveal diverse histological patterns, mitotic activity, and distinct methylation profiles. Surgical treatment is the gold standard, but when limited to partial removal, radiotherapy becomes crucial. While surgical approaches are standardized, due to the low prevalence of the pathology and absence of randomized prospective studies, there are no shared guidelines about radiation treatment modalities.
CONCLUSION
Surgical removal remains pivotal, demanding a personalized approach based on the tumor extension. This review underscores the considerable variability in treatment approaches and reported survival rates within the existing literature, emphasizing the need for ongoing research to better define optimal therapeutic strategies and prognostic factors for PPTIDs, aiming for further and more detailed stratification among them.
PubMed: 38592098
DOI: 10.3390/jcm13051266 -
Frontiers in Neural Circuits 2024Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to... (Review)
Review
Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to the suprachiasmatic nucleus is the retinohypothalamic tract, with additional inputs from the intergeniculate leaflet pathway, the serotonergic afferent from the raphe, and other hypothalamic regions. Within the suprachiasmatic nucleus, two of the major subtypes are vasoactive intestinal polypeptide (VIP)-positive neurons and arginine-vasopressin (AVP)-positive neurons. VIP neurons are important for light entrainment and synchronization of suprachiasmatic nucleus neurons, whereas AVP neurons are important for circadian period determination. Output targets of the suprachiasmatic nucleus include the hypothalamus (subparaventricular zone, paraventricular hypothalamic nucleus, preoptic area, and medial hypothalamus), the thalamus (paraventricular thalamic nuclei), and lateral septum. The suprachiasmatic nucleus also sends information through several brain regions to the pineal gland. The olfactory bulb is thought to be able to generate a circadian rhythm without the suprachiasmatic nucleus. Some reports indicate that circadian rhythms of the olfactory bulb and olfactory cortex exist in the absence of the suprachiasmatic nucleus, but another report claims the influence of the suprachiasmatic nucleus. The regulation of circadian rhythms by sensory inputs other than light stimuli, including olfaction, has not been well studied and further progress is expected.
Topics: Animals; Suprachiasmatic Nucleus; Hypothalamus; Circadian Rhythm; Vasoactive Intestinal Peptide; Sleep; Arginine Vasopressin
PubMed: 38590628
DOI: 10.3389/fncir.2024.1385908 -
Zoological Science Feb 2024Melatonin (-acetyl-5-methoxytryptamine) is an indolamine that is synthesized from tryptophan in the pineal glands of vertebrates through four enzymatic reactions....
Melatonin (-acetyl-5-methoxytryptamine) is an indolamine that is synthesized from tryptophan in the pineal glands of vertebrates through four enzymatic reactions. Melatonin is a quite unique bioactive substance, characterized by a combination of both receptor-mediated and receptor-independent actions, which promote the diverse effects of melatonin. One of the main functions of melatonin, via its membrane receptors, is to regulate the circadian or seasonal rhythm. In mammals, light information, which controls melatonin synthesis, is received in the eye, and transmitted to the pineal gland, via the suprachiasmatic nucleus, where the central clock is located. Alternatively, in many vertebrates other than mammals, the pineal gland cells, which are involved in melatonin synthesis and secretion and in the circadian clock, directly receive light. Recently, it has been reported that melatonin possesses several metabolic functions, which involve bone and glucose, in addition to regulating the circadian rhythm. Melatonin improves bone strength by inhibiting osteoclast activity. It is also known to maintain brain activity during sleep by increasing glucose uptake at night, in an insulin-independent manner. Moreover, as a non-receptor-mediated action, melatonin has antioxidant properties. Melatonin has been proven to be a potent free radical scavenger and a broad-spectrum antioxidant, even protecting organisms against radiation from space. Melatonin is a ubiquitously distributed molecule and is found in bacteria, unicellular organisms, fungi, and plants. It is hypothesized that melatonin initially functioned as an antioxidant, then, in vertebrates, it combined this role with the ability to regulate rhythm and metabolism, via its receptors.
Topics: Animals; Melatonin; Antioxidants; Vertebrates; Circadian Clocks; Mammals
PubMed: 38587523
DOI: 10.2108/zs230057 -
Heliyon Apr 2024Diabetes mellitus (DM) is a chronic metabolic disease marked by hyperglycemia due to insulin deficiency or insulin resistance leading to many chronic complications. It...
Diabetes mellitus (DM) is a chronic metabolic disease marked by hyperglycemia due to insulin deficiency or insulin resistance leading to many chronic complications. It is thus important to manage diabetes effectively in order to prevent and or delay these complications. Melatonin is produced by the pineal gland and regulates the wake-sleep circadian rhythm. Existing evidence suggests that melatonin may be effective in the management of DM. However, the evidence on the mechanism of the beneficial effect melatonin as a treatment for DM is limited. In this study, we investigated the effect of melatonin treatment on blood glucose, insulin (INS), AKT and superoxide dismutase (SOD) gene levels in diabetic rats. Non-diabetic and diabetic rats were treated orally for 4 weeks with either 25 mg or 50 mg/kg body weight of melatonin. At the end of the study, pancreatic and liver tissues morphology, glucose homeostasis, serum insulin and SOD levels, hepatic gene and protein expression of SOD as protecting antioxidant enzyme and AKT as central element involved in PI3K/AKT insulin signaling pathway were estimated. Melatonin treated diabetic rats showed reduced hyperglycemia, and increased serum insulin and SOD levels. In addition, melatonin induced an increased gene and protein expression of SOD and AKT. In conclusion, melatonin may play a role in treating diabetic rats via stimulation of insulin secretion, insulin signaling and reduction in oxidative stress.
PubMed: 38586324
DOI: 10.1016/j.heliyon.2024.e28639 -
Life Sciences Jun 2024Sepsis is a life-threatening condition manifested by organ dysfunction caused by a dysregulated host response to infection. Lung, brain, liver, kidney, and heart are... (Review)
Review
Sepsis is a life-threatening condition manifested by organ dysfunction caused by a dysregulated host response to infection. Lung, brain, liver, kidney, and heart are among the affected organs. Sepsis-induced cardiomyopathy is a common cause of death among septic patients. Sepsis-induced cardiomyopathy is characterized by an acute and reversible significant decline in biventricular both systolic and diastolic function. This is accompanied by left ventricular dilatation. The pathogenesis underlying sepsis-induced cardiomyopathy is multifactorial. Hence, targeting an individual pathway may not be effective in halting the extensive dysregulated immune response. Despite major advances in sepsis management strategies, no effective pharmacological strategies have been shown to treat or even reverse sepsis-induced cardiomyopathy. Melatonin, namely, N-acetyl-5-methoxytryptamine, is synthesized in the pineal gland of mammals and can also be produced in many cells and tissues. Melatonin has cardioprotective, neuroprotective, and anti-tumor activity. Several literature reviews have explored the role of melatonin in preventing sepsis-induced organ failure. Melatonin was found to act on different pathways that are involved in the pathogenesis of sepsis-induced cardiomyopathy. Through its antimicrobial, anti-inflammatory, and antioxidant activity, it offers a potential role in sepsis-induced cardiomyopathy. Its antioxidant activity is through free radical scavenging against reactive oxygen and nitrogen species and modulating the expression and activity of antioxidant enzymes. Melatonin anti-inflammatory activities control the overactive immune system and mitigate cytokine storm. Also, it mitigates mitochondrial dysfunction, a major mechanism involved in sepsis-induced cardiomyopathy, and thus controls apoptosis. Therefore, this review discusses melatonin as a promising drug for the management of sepsis-induced cardiomyopathy.
Topics: Melatonin; Sepsis; Humans; Cardiomyopathies; Animals; Antioxidants; Cardiotonic Agents
PubMed: 38580195
DOI: 10.1016/j.lfs.2024.122611 -
Current Medicinal Chemistry Mar 2024Alzheimer's Disease (AD) is the most common cause of dementia, afflicting over 5 million people in the United States. There remains a lack of effective disease--...
Alzheimer's Disease (AD) is the most common cause of dementia, afflicting over 5 million people in the United States. There remains a lack of effective disease-- modifying treatments for AD beyond a few approved drugs that provide temporary symptomatic relief. Melatonin is an endogenous hormone mainly produced by the pineal gland that regulates circadian rhythms and possesses antioxidant and anti-inflammatory properties. An expansive body of research over the past few decades has investigated melatonin as a promising therapeutic agent for AD based on its ability to target multiple pathophysiological processes implicated in AD progression. In this comprehensive review, we summarize extensive evidence from cellular and animal models that has uncovered the diverse mechanisms underpinning melatonin's neuroprotective efficacy against AD pathology. We also synthesize clinical studies examining melatonin's effects on AD progression and symptoms. Additionally, we discuss how melatonin's multimodal mechanisms, favorable safety profile, and ability to synergize with conventional therapies heighten its potential as an effective therapeutic strategy for AD. Rigorously designed clinical trials incorporating physiological biomarkers are warranted to definitively establish melatonin's disease-modifying effects. Nevertheless, the considerable preclinical data support further exploration of melatonin as a therapeutic agent for AD.
PubMed: 38561619
DOI: 10.2174/0109298673286807240326085736 -
Journal of Pineal Research Apr 2024Homeobox genes encode transcription factors that are widely known to control developmental processes. This is also the case in the pineal gland, a neuroendocrine brain... (Review)
Review
Homeobox genes encode transcription factors that are widely known to control developmental processes. This is also the case in the pineal gland, a neuroendocrine brain structure devoted to nighttime synthesis of the hormone melatonin. Thus, in accordance with high prenatal gene expression, knockout studies have identified a specific set of homeobox genes that are essential for development of the pineal gland. However, as a special feature of the pineal gland, homeobox gene expression persists into adulthood, and gene product abundance exhibits 24 h circadian rhythms. Recent lines of evidence show that some homeobox genes even control expression of enzymes catalyzing melatonin synthesis. We here review current knowledge of homeobox genes in the rodent pineal gland and suggest a model for dual functions of homeobox gene-encoded transcription factors in developmental and circadian mature neuroendocrine function.
Topics: Animals; Pineal Gland; Genes, Homeobox; Melatonin; Rodentia; Transcription Factors; Circadian Rhythm
PubMed: 38558122
DOI: 10.1111/jpi.12950