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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 -
Case Reports in Oncology 2024Intracranial germinomas mainly arise in the pineal gland or neurohypophyseal region. The basal ganglia have been reported as the site of occurrence for ectopic...
INTRODUCTION
Intracranial germinomas mainly arise in the pineal gland or neurohypophyseal region. The basal ganglia have been reported as the site of occurrence for ectopic germinomas, whereas other sites have been rarely described. We experienced a case of multifocal ectopic germinoma that arose in the septum pellucidum and the dorsal brain stem, not including the pineal gland, neurohypophysis, and basal ganglia of ectopic germinoma in a pregnant woman.
CASE PRESENTATION
The patient initially presented to our institution with complaints of diplopia in the past 14 weeks of gestation, and imaging later revealed two intracranial neoplastic lesions, with one lesion involving the septum pellucidum and the other involving the dorsal brainstem. Both tumors were partially excised via a transcortical approach. Based on the results of pathology and immunohistochemistry, the patient was diagnosed with germinoma, and the intraoperative spinal fluid cytology was class V in Papanicolaou classification. The patient received three courses of ifosfamide, carboplatin, and etoposide together with whole-brain irradiation, which resulted in complete elimination of the tumors. No evidence of recurrence was identified after 18 months.
CONCLUSION
The results illustrated the need to consider germinoma in the differential diagnosis if the lesions involve midline structures such as the septum pellucidum or dorsal brainstem. Given the rarity of germinoma arising outside the pineal gland and neurohypophyseal region, these findings provide key insights into the diagnosis and treatment of this disease.
PubMed: 38549623
DOI: 10.1159/000538088 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2024Currently, endoscopic third ventriculostomy and simultaneous biopsy of deep midline brain tumors are a generally accepted option in neurooncology. Nevertheless,...
BACKGROUND
Currently, endoscopic third ventriculostomy and simultaneous biopsy of deep midline brain tumors are a generally accepted option in neurooncology. Nevertheless, effectiveness of this surgery and diagnostic accuracy of biopsy are not without drawbacks. An alternative to endoscopic surgery may be simultaneous microsurgical third ventriculostomy and biopsy of deep midline tumors.
OBJECTIVE
To evaluate effectiveness and safety of burr hole microsurgical third ventriculostomy in the treatment of deep midline brain tumors.
MATERIAL AND METHODS
We used transcortical (25 cases) and transcallosal (8 cases) approaches for microsurgical third ventriculostomy.
RESULTS
Initially scheduled biopsy was performed in 19 cases, partial resection in 6 cases, subtotal resection in 4 cases and total resection in 4 cases. All patients underwent microsurgical third ventriculostomy. In 12 cases, stenting of stoma was performed in addition to ventriculostomy. Biopsy was informative in all cases. Postoperative follow-up period ranged from 3 to 44 months (mean 29 months). There was no postoperative hydrocephalus and need for shunting procedure.
CONCLUSION
Burr hole microsurgery may be an alternative to endoscopic surgery for the treatment of pineal, periaqueductal and third ventricular tumors.
Topics: Humans; Ventriculostomy; Third Ventricle; Brain Neoplasms; Endoscopy; Pineal Gland; Hydrocephalus; Neuroendoscopy
PubMed: 38549405
DOI: 10.17116/neiro2024880215 -
Clinical Neurology and Neurosurgery May 2024Pineal region lesions can result in tectal plate compression, hydrocephalus, and associated symptoms including headache, Parinaud's Syndrome, and epileptic phenomena. No... (Review)
Review
INTRODUCTION
Pineal region lesions can result in tectal plate compression, hydrocephalus, and associated symptoms including headache, Parinaud's Syndrome, and epileptic phenomena. No studies have looked at the relationship between these lesions and the autonomic nervous system.
METHODS
To evaluate the clinical presentation of pineal lesions secondary to tectal plate compression with a focus on autonomic dysfunction, a systematic review was completed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Case reports and prospective and retrospective studies on patients with pineal or tectal region lesions were included.
RESULTS
Of 73 identified studies, 43 underwent full text screening. 26 studies (n=363 patients; age range 0-69 years) were included. 47.1% of patients were male (n=171). Obstructive hydrocephalus was identified in 119 patients (32.8%). The most common symptom was headache (n=228, 62.8%), followed by epileptic phenomena (n=76, 20.9%). Vision related symptoms were identified in 88 patients (24.2%). 251 patients (69.1%) had symptoms associated with autonomic dysfunction including dizziness, nausea, pupillary dysfunction, photophobia and fatigue. Of the 200 (55%) patients who underwent surgery, 135 patients (67.5%) had improved or resolved symptoms post-operatively, including 120 patients with improved autonomic dysfunction symptoms.
CONCLUSIONS
Though these lesions are most characterized by Parinaud's syndrome and hydrocephalus, this review suggests dysfunction of the autonomic nervous system may be at play and require consideration at initial presentation and treatment.
Topics: Humans; Autonomic Nervous System Diseases; Hydrocephalus; Pineal Gland; Male; Adult; Headache; Tectum Mesencephali; Adolescent; Child, Preschool; Aged; Child; Middle Aged; Young Adult; Female
PubMed: 38547628
DOI: 10.1016/j.clineuro.2024.108247 -
Biomolecules Mar 2024In all mammals, the circulating pool of MLTs is synthesized in the pineal gland during the night's darkness hours. Its main function is synchronizing the organism in the... (Review)
Review
In all mammals, the circulating pool of MLTs is synthesized in the pineal gland during the night's darkness hours. Its main function is synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm or circulate, and plays a detoxifying and cytoprotective role. Circulating MLT may stimulate both innate and acquired immune responses through its circadian action and by activating high-affinity receptors on immunocompetent cells. Extra-pineal MLT may have antioxidant and anti-inflammatory effects that dampen the innate immune response. These two seemingly divergent roles may be considered to be two sides of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effects of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility of integrating the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite of the fact that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.
Topics: Animals; Humans; Melatonin; Pineal Gland; Antioxidants; Circadian Rhythm; Parasitic Diseases; Anti-Inflammatory Agents; Mammals
PubMed: 38540774
DOI: 10.3390/biom14030356 -
Clocks & Sleep Feb 2024In humans, the nocturnal secretion of melatonin by the pineal gland is suppressed by ocular exposure to light. In the laboratory, melatonin suppression is a biomarker...
In humans, the nocturnal secretion of melatonin by the pineal gland is suppressed by ocular exposure to light. In the laboratory, melatonin suppression is a biomarker for this neuroendocrine pathway. Recent work has found that individuals differ substantially in their melatonin-suppressive response to light, with the most sensitive individuals being up to 60 times more sensitive than the least sensitive individuals. Planning experiments with melatonin suppression as an outcome needs to incorporate these individual differences, particularly in common resource-limited scenarios where running within-subjects studies at multiple light levels is costly and resource-intensive and may not be feasible with respect to participant compliance. Here, we present a novel framework for virtual laboratory melatonin suppression experiments, incorporating a Bayesian statistical model. We provide a Shiny web app for power analyses that allows users to modify various experimental parameters (sample size, individual-level heterogeneity, statistical significance threshold, light levels), and simulate a systematic shift in sensitivity (e.g., due to a pharmacological or other intervention). Our framework helps experimenters to design compelling and robust studies, offering novel insights into the underlying biological variability in melatonin suppression relevant for practical applications.
PubMed: 38534797
DOI: 10.3390/clockssleep6010009 -
Brain Pathology (Zurich, Switzerland) May 2024
Topics: Female; Humans; Pineal Gland; Pinealoma; Brain Neoplasms
PubMed: 38527786
DOI: 10.1111/bpa.13258 -
Biomedicine & Pharmacotherapy =... May 2024Melatonin is a highly conserved molecule produced in the human pineal gland as a hormone. It is known for its essential biological effects, such as antioxidant activity,... (Review)
Review
Melatonin is a highly conserved molecule produced in the human pineal gland as a hormone. It is known for its essential biological effects, such as antioxidant activity, circadian rhythm regulator, and immunomodulatory effects. The gut is one of the primary known sources of melatonin. The gut microbiota helps produce melatonin from tryptophan, and melatonin has been shown to have a beneficial effect on gut barrier function and microbial population. Dysbiosis of the intestinal microbiota is associated with bacterial imbalance and decreased beneficial microbial metabolites, including melatonin. In this way, low melatonin levels may be related to several human diseases. Melatonin has shown both preventive and therapeutic effects against various conditions, including neurological diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This review was aimed to discuss the role of melatonin in the body, and to describe the possible relationship between gut microbiota and melatonin production, as well as the potential therapeutic effects of melatonin on neurological diseases.
Topics: Melatonin; Humans; Gastrointestinal Microbiome; Nervous System Diseases; Animals; Dysbiosis
PubMed: 38518598
DOI: 10.1016/j.biopha.2024.116487 -
Chronobiology International Mar 2024The light/dark cycle, known as the photoperiod, plays a crucial role in influencing various physiological activities in fish, such as growth, feeding and reproduction....
The light/dark cycle, known as the photoperiod, plays a crucial role in influencing various physiological activities in fish, such as growth, feeding and reproduction. However, the underlying mechanisms of this influence are not fully understood. This study focuses on exploring the impact of different light regimes (LD: 12 h of light and 12 h of darkness; LL: 24 h of light and 0 h of darkness; DD: 0 h of light and 24 h of darkness) on the expression of clock genes () and the secretion of hormones (melatonin, GnRH, NPY) in the large yellow croaker, . Real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assays were utilized to assess how photoperiod variations affect clock gene expression and hormone secretion. The results indicate that changes in photoperiod can disrupt the rhythmic patterns of clock genes, leading to phase shifts and decreased expression. Particularly under LL conditions, the pineal and genes lose their rhythmicity, while and genes exhibit phase shifts, highlighting the importance of dark phase entrainment for maintaining rhythmicity. Additionally, altered photoperiod affects the neuroendocrine system of . In comparison to the LD condition, LL and DD treatments showed a phase delay of GnRH secretion and an acceleration of NPY synthesis. These findings provide valuable insights into the regulatory patterns of circadian rhythms in fish and may contribute to optimizing the light environment in the farming industry.
Topics: Animals; Circadian Rhythm; Photoperiod; Pineal Gland; Melatonin; Gene Expression; Perciformes; Gonadotropin-Releasing Hormone
PubMed: 38516993
DOI: 10.1080/07420528.2024.2315215