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Drug Design, Development and Therapy 2024Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major... (Review)
Review
Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major contributors to visual impairment and blindness worldwide. The development and implementation of effective strategies for managing and preventing the onset and progression of these diseases are crucial for preserving patients' visual acuity. Melatonin, a neurohormone primarily produced by the pineal gland, exhibits properties such as circadian rhythm modulation, antioxidant activity, anti-inflammatory effects, and neuroprotection within the ocular environment. Furthermore, melatonin has been shown to suppress neovascularization and reduce vascular leakage, both of which are critical in the pathogenesis of degenerative fundus lesions. Consequently, melatonin emerges as a promising therapeutic candidate for degenerative ocular diseases. This review provides a comprehensive overview of melatonin synthesis, its localization within ocular tissues, and its mechanisms of action, particularly in regulating melatonin production, thereby underscoring its potential as a therapeutic agent for degenerative fundus diseases.
Topics: Melatonin; Humans; Diabetic Retinopathy; Macular Degeneration; Animals; Fundus Oculi; Antioxidants
PubMed: 38911030
DOI: 10.2147/DDDT.S471525 -
Nutrients May 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder identified by impairments in common social interactions and repetitive behaviors. In ASD patients,...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder identified by impairments in common social interactions and repetitive behaviors. In ASD patients, substantial morphological alterations have been observed in the hippocampus, which represents an important region for the development of social skills. Melatonin, commonly found in many foods and plants, is also produced by the pineal gland. This indolamine, known to regulate the circadian rhythm, shows antioxidant and anti-inflammatory properties. We therefore hypothesized that melatonin may reduce oxidative stress and inflammation in the hippocampus of ASD patients. We explored our hypothesis using the BTBR mouse, a well-regarded murine transgenic model for ASD. Immediately after weaning, male BTBR and C57BL/6 mice underwent an 8-week treatment with melatonin or vehicle. Later, through immunohistochemistry and the immunoblotting analysis of the hippocampus, we evaluated the overall expression and cellular localization of Nrf2 and SOD1, two enzymes involved in the oxidative stress response. Similarly, we evaluated NLRP3 and NFkB, two mediators of inflammation, and GAD67, an enzyme responsible for the synthesis of GABA. Ultimately, we addressed melatonin's potential to regulate iron metabolism through a DAB-enhanced Perls reaction assay. Results showed melatonin's potential for modulating the analyzed markers in BTBR mice, suggesting a potential neuroprotective effect in ASD patients.
Topics: Animals; Melatonin; Hippocampus; Male; Neuroprotective Agents; Mice; Mice, Inbred C57BL; Oxidative Stress; Disease Models, Animal; Autism Spectrum Disorder; Antioxidants; Mice, Transgenic; NF-E2-Related Factor 2; Inflammation
PubMed: 38892585
DOI: 10.3390/nu16111652 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Jun 2024Wound healing involves the repair of skin and other soft tissues after an injury. Royal jelly, a product of bees, possesses antioxidant, anti-inflammatory,... (Comparative Study)
Comparative Study
BACKGROUND
Wound healing involves the repair of skin and other soft tissues after an injury. Royal jelly, a product of bees, possesses antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Melatonin, a circadian indoleamine, is produced in the pineal gland and other organs. This study explores the effects of melatonin and royal jelly, both individually and combined, on wound healing in geriatric and young mice.
METHODS
The study includes 90 Balb/C mice divided into ten groups to assess the effects of royal jelly and melatonin on wound healing. Royal jelly was applied topically at a concentration of 300 mg/kg. Melatonin was formulated in a vaseline-based pomade at a concentration of 5 mg/kg. The substances were applied either separately or in combination to wounds created on the mice.
RESULTS
Both substances significantly enhanced wound healing at a macroscopic level in both age groups. Melatonin was found to be more effective during the initial wound formation process, whereas royal jelly was more beneficial during the granulation phase. However, significant results at a histopathological level were observed only in geriatric animals.
CONCLUSION
The findings suggest a potential new therapeutic approach to enhance wound healing, particularly in elderly individuals. However, these findings need to be supported through further research and clinical trials.
Topics: Animals; Melatonin; Wound Healing; Mice; Fatty Acids; Mice, Inbred BALB C; Male; Disease Models, Animal; Antioxidants; Wounds and Injuries
PubMed: 38863293
DOI: 10.14744/tjtes.2024.83307 -
Pharmacological Research Jul 2024Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates... (Review)
Review
Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions.
Topics: Melatonin; Humans; Animals; Eye Diseases; Eye; Blood-Retinal Barrier
PubMed: 38862072
DOI: 10.1016/j.phrs.2024.107253 -
Sleep Medicine: X Dec 2024Melatonin, the primary hormone secreted by the pineal gland, regulates central and peripheral oscillators and adapts the internal environment to the external one through...
Melatonin, the primary hormone secreted by the pineal gland, regulates central and peripheral oscillators and adapts the internal environment to the external one through MT1 and MT2 receptors. The authors present a case of 16-year-old male intentionally overdosed on 900mg of melatonin (180 tablets) and 10 tablets of 0.5mg alprazolam. Admitted to the emergency department, he was extremely drowsy and minimally responsive with a Glasgow coma scale score of 8/15. Vital signs were stable, and no renal or liver dysfunction was noted. Elevated total leucocyte count and positive benzodiazepine urine test were observed. Gastric lavage was performed, and toxicology reports showed blood alprazolam levels at 0.15 mg/litre eight hours post-overdose. The patient regained consciousness 32 hours post-ingestion and was transferred to the psychiatry unit. This case underscores the increasing abuse of melatonin due to its easy availability and lack of regulation. Although melatonin has a low toxicity potential, side effects and interactions with other drugs can be severe. Supportive measures and vital sign control are crucial in overdose treatment.
PubMed: 38846909
DOI: 10.1016/j.sleepx.2024.100116 -
Physiological Research May 2024The Institute of Physiology of the Czech Academy of Sciences (CAS) has been involved in the field of chronobiology, i.e., in research on temporal regulation of...
From the Pineal Gland to the Central Clock in the Brain: Beginning of Studies of the Mammalian Biological Rhythms in the Institute of Physiology of the Czech Academy of Sciences.
The Institute of Physiology of the Czech Academy of Sciences (CAS) has been involved in the field of chronobiology, i.e., in research on temporal regulation of physiological processes, since 1970. The review describes the first 35 years of the research mostly on the effect of light and daylength, i.e., photoperiod, on entrainment or resetting of the pineal rhythm in melatonin production and of intrinsic rhythms in the central biological clock. This clock controls pineal and other circadian rhythms and is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. During the early chronobiological research, many original findings have been reported, e.g. on mechanisms of resetting of the pineal rhythm in melatonin production by short light pulses or by long exposures of animals to light at night, on modulation of the nocturnal melatonin production by the photoperiod or on the presence of high affinity melatonin binding sites in the SCN. The first evidence was given that the photoperiod modulates functional properties of the SCN and hence the SCN not only controls the daily programme of the organism but it may serve also as a calendar measuring the time of a year. During all the years, the chronobiological community has started to talk about "the Czech school of chronobiology". At present, the today´s Laboratory of Biological Rhythms of the Institute of Physiology CAS continues in the chronobiological research and the studies have been extended to the entire circadian timekeeping system in mammals with focus on its ontogenesis, entrainment mechanisms and circadian regulation of physiological functions. Key words: Pineal, Melatonin, AA-NAT rhythm, Light entrainment, Photoperiod, SCN clock.
PubMed: 38836462
DOI: No ID Found -
Neurology India Mar 2024
Topics: Humans; Epidermal Cyst; Pineal Gland; Magnetic Resonance Imaging; Male; Endoscopy; Neuroendoscopy
PubMed: 38817170
DOI: 10.4103/neurol-india.Neurol-India-D-23-00494 -
Frontiers in Neuroanatomy 2024Multiple sclerosis has a complex pathophysiology, and numerous risk factors can contribute to its development, like exposure to sunlight that is associated with serum...
INTRODUCTION
Multiple sclerosis has a complex pathophysiology, and numerous risk factors can contribute to its development, like exposure to sunlight that is associated with serum levels of melatonin. The aim of this study was to determine whether the volume of the pineal gland, assessed by magnetic resonance imaging (MRI), correlated with the presence of multiple sclerosis.
METHODS
This retrospective study included a total of 394 patients. Subjects were divided into two groups: the first group consisted of 188 patients with a definite diagnosis of multiple sclerosis (based on revised McDonald criteria) and the second group consisted of 206 healthy controls. To examine the influence of age on pineal gland volume, we stratified the whole sample into three age groups: first involved patients under 20 years, second patients between 20 and 40 years, and third group included patients over 40 years. The maximum length (L) and height (H) of the pineal gland were measured on the T1-weighted sagittal images, and the width (W) was measured on the T2-weighted coronal or axial images. The volume of the gland was calculated as an approximation to an ellipse, according to the formula = ( × × )/2.
RESULTS
Pineal gland volume of female multiple sclerosis (MS) patients ( = 129) was significantly lower than in healthy females ( = 123) ( = 0.013; < 0.05), unlike in males where there is not such difference. Also, pineal gland volume is not age-dependent, and the observed smaller pineal gland in MS patients can reliably be attributed to the disease itself. Additionally, large pineal gland size, especially over 62.83 mm when compared to pineal gland volume below 31.85 mm is associated with more than double reduced risk of multiple sclerosis (OR 0.42; = 0.003).
DISCUSSION
Our results suggest that women with multiple sclerosis have smaller pineal glands that can theoretically be explained by a lack of input stimuli and the resultant decrease in gland volume. Additionally, the risk of multiple sclerosis is reduced in larger pineal gland volumes.
PubMed: 38813079
DOI: 10.3389/fnana.2024.1386295 -
Frontiers in Endocrinology 2024This article discusses data showing that mammals, including humans, have two sources of melatonin that exhibit different functions. The best-known source of melatonin,... (Review)
Review
This article discusses data showing that mammals, including humans, have two sources of melatonin that exhibit different functions. The best-known source of melatonin, herein referred to as Source #1, is the pineal gland. In this organ, melatonin production is circadian with maximal synthesis and release into the blood and cerebrospinal fluid occurring during the night. Of the total amount of melatonin produced in mammals, we speculate that less than 5% is synthesized by the pineal gland. The melatonin rhythm has the primary function of influencing the circadian clock at the level of the suprachiasmatic nucleus (the CSF melatonin) and the clockwork in all peripheral organs (the blood melatonin) via receptor-mediated actions. A second source of melatonin (Source # 2) is from multiple tissues throughout the body, probably being synthesized in the mitochondria of these cells. This constitutes the bulk of the melatonin produced in mammals and is concerned with metabolic regulation. This review emphasizes the action of melatonin from peripheral sources in determining re-dox homeostasis, but it has other critical metabolic effects as well. Extrapineal melatonin synthesis does not exhibit a circadian rhythm and it is not released into the blood but acts locally in its cell of origin and possibly in a paracrine matter on adjacent cells. The factors that control/influence melatonin synthesis at extrapineal sites are unknown. We propose that the concentration of melatonin in these cells is determined by the subcellular redox state and that melatonin synthesis may be inducible under stressful conditions as in plant cells.
Topics: Melatonin; Humans; Animals; Circadian Rhythm; Pineal Gland; Suprachiasmatic Nucleus
PubMed: 38808108
DOI: 10.3389/fendo.2024.1414463 -
Nutrients May 2024Breastfeeding is the most appropriate source of a newborn's nutrition; among the plethora of its benefits, its modulation of circadian rhythmicity with melatonin as a... (Review)
Review
Breastfeeding is the most appropriate source of a newborn's nutrition; among the plethora of its benefits, its modulation of circadian rhythmicity with melatonin as a potential neuroendocrine transducer has gained increasing interest. Transplacental transfer assures melatonin provision for the fetus, who is devoid of melatonin secretion. Even after birth, the neonatal pineal gland is not able to produce melatonin rhythmically for several months (with an even more prolonged deficiency following preterm birth). In this context, human breast milk constitutes the main natural source of melatonin: diurnal dynamic changes, an acrophase early after midnight, and changes in melatonin concentrations according to gestational age and during the different stages of lactation have been reported. Understudied thus far are the factors impacting on (changes in) melatonin content in human breast milk and their clinical significance in chronobiological adherence in the neonate: maternal as well as environmental aspects have to be investigated in more detail to guide nursing mothers in optimal feeding schedules which probably means a synchronized instead of mistimed feeding practice. This review aims to be thought-provoking regarding the critical role of melatonin in chrononutrition during breastfeeding, highlighting its potential in circadian entrainment and therefore optimizing (neuro)developmental outcomes in the neonatal setting.
Topics: Humans; Melatonin; Milk, Human; Circadian Rhythm; Breast Feeding; Female; Infant, Newborn; Lactation; Infant Nutritional Physiological Phenomena
PubMed: 38794660
DOI: 10.3390/nu16101422