Melatonin treatment decreases c-fos expression in a headache model induced by capsaicin

The aim of the present work was to analyze c-fos response within the trigeminal nucleus caudalis (TNC) of pinealectomized rats and animals that received intraperitoneal melatonin, after intracisternal infusion of capsaicin, used to induce intracranial trigeminovascular stimulation. Experimental groups consisted of animals that received vehicle solution (saline-ethanol-Tween 80, 8:1:1, diluted 1:50) only (VEI, n = 5); animals that received capsaicin solution (200 nM) only (CAP, n = 6); animals submitted to pinealectomy (PX, n = 5); sham-operated animals (SH, n = 5); animals submitted to pinealectomy followed by capsaicin stimulation (200 nM) after 15 days (PX + CAP, n = 7); and animals that received capsaicin solution (200 nM) and intraperitoneal melatonin (10 mg/kg) (CAP + MEL, n = 5). Control rats, receiving vehicle in the cisterna magna, showed a small number of c-fos-positive cells in the TNC (layer I/II) as well as the sham-operated and pinealectomized rats, when compared to animals stimulated by capsaicin. On the other hand, pinealectomized rats, which received capsaicin, presented the highest number of c-fos-positive cells. Animals receiving capsaicin and melatonin treatment had similar expression of the vehicle group. Our data provide experimental evidence to support the role of melatonin and pineal gland in the pathophysiology of neurovascular headaches.Universidade Federal de São Paulo, Escola Paulista Med, Dept Neurol Neurocirurgia, São Paulo, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Fisiol Biofis, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Neurol Neurocirurgia, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, São Paulo, BrazilWeb of Scienc

Perineuronal satellite neuroglia in the telencephalon of New Caledonian crows and other Passeriformes: evidence of satellite glial cells in the central nervous system of healthy birds?

Glia have been implicated in a variety of functions in the central nervous system, including the control of the neuronal extracellular space, synaptic plasticity and transmission, development and adult neurogenesis. Perineuronal glia forming groups around neurons are associated with both normal and pathological nervous tissue. Recent studies have linked reduction in the number of perineuronal oligodendrocytes in the prefrontal cortex with human schizophrenia and other psychiatric disorders. Therefore, perineuronal glia may play a decisive role in homeostasis and normal activity of the human nervous system.Here we report on the discovery of novel cell clusters in the telencephala of five healthy Passeriforme, one Psittaciform and one Charadriiforme bird species, which we refer to as Perineuronal Glial Clusters (PGCs). The aim of this study is to describe the structure and distribution of the PGCs in a number of avian species.PGCs were identified with the use of standard histological procedures. Heterochromatin masses visible inside the nuclei of these satellite glia suggest that they may correspond to oligodendrocytes. PGCs were found in the brains of nine New Caledonian crows, two Japanese jungle crows, two Australian magpies, two Indian mynah, three zebra finches (all Passeriformes), one Southern lapwing (Charadriiformes) and one monk parakeet (Psittaciformes). Microscopic survey of the brain tissue suggests that the largest PGCs are located in the hyperpallium densocellulare and mesopallium. No clusters were found in brain sections from one Gruiform (purple swamphen), one Strigiform (barn owl), one Trochiliform (green-backed firecrown), one Falconiform (chimango caracara), one Columbiform (pigeon) and one Galliform (chick).Our observations suggest that PGCs in Aves are brain region- and taxon-specific and that the presence of perineuronal glia in healthy human brains and the similar PGCs in avian gray matter is the result of convergent evolution. The discovery of PGCs in the zebra finch is of great importance because this species has the potential to become a robust animal model in which to study the function of neuron-glia interactions in healthy and diseased adult brains

The Angiotensin-melatonin axis

Accumulating evidence indicates that various biological and neuroendocrine circadian rhythms may be disrupted in cardiovascular and metabolic disorders. These circadian alterations may contribute to the progression of disease. Our studies direct to an important role of angiotensin II and melatonin in the modulation of circadian rhythms. The brain renin-angiotensin system (RAS) may modulate melatonin synthesis, a hormone with well-established roles in regulating circadian rhythms. Angiotensin production in the central nervous system may not only influence hypertension but also appears to affect the circadian rhythm of blood pressure. Drugs acting on RAS have been proven effective in the treatment of cardiovascular and metabolic disorders including hypertension and diabetes mellitus (DM). On the other hand, since melatonin is capable of ameliorating metabolic abnormalities in DM and insulin resistance, the beneficial effects of RAS blockade could be improved through combined RAS blocker and melatonin therapy. Contemporary research is evidencing the existence of specific clock genes forming central and peripheral clocks governing circadian rhythms. Further research on the interaction between these two neurohormones and the clock genes governing circadian clocks may progress our understanding on the pathophysiology of disease with possible impact on chronotherapeutic strategies

Melatonin action on luteal - granulosa cells in women with marital infertility undergoing in vitro fertilization

Introduction of the subject: Melatonin is a hormone related to the light-dark cycle and it plays an influential role in the reproductive system. In humans, researchers have shown there is three times more melatonin in follicular fluid than in the blood flow, suggesting the influence of the hormone on follicular maturation. However, little is known about melatonin action on granulosa cells in women with infertility, especially the molecular mechanisms involved. We are, therefore, conducting this study to evaluate melatonin action pathways in granulosa cells in the ovaries of women with infertility. To achieve our aim, we will use molecular biology, involving diverse signaling pathways, such as angiogenesis. Objective(s): to analyze melatonin action on luteal - granulosa cells in women with marital infertility undergoing in vitro fertilization. Methodology: For this, 68 patients, aged between 20 and 35 years, attended at the Human Reproduction Sector of the Federal University of São Paulo, were submitted to in vitro fertilization treatment. After all preparatory procedures were performed, luteal granulosa cells were removed and routed to the cell culture. The cells were divided into four groups: a) control; b) 0.1 μM melatonin; c) 1 μM melatonin; d) melatonin at 10μM. After a period of 10 days, the cells were trypsinized for extraction of the total RNA and later analysis of the gene expression by Real Time PCR of the angiogenesis signaling pathway. Results: Our data evaluated 96 genes, which are related to the angiogenesis pathway. The results of transcriptional expression showed important genes involved in this pathway that are hypo or hyperexpressed after treatment with melatonin. The main hyperexpressed genes were: fibroblast growth factor 1 (FGF1) genes; interleukin 1-beta (IL1B); receptor tyrosine kinase (VEGFR-2); folliculogenesis regulating genes (TGFB1). They act in the dynamics of follicular growth. On the other hand, the genes inducing factor 1-alpha (HIF1A), fibroblast growth factor 2 (FGF2), insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGFA) melatonin decreased its expression. Discussion and conclusion of the results: It is concluded that melatonin in high concentration (above 1 μM) may have dual function in increasing the expression of some growth factors and cytokines, in the decrease of other genes and mechanism of physiological compensation and also modulates negative angiogenesis, mainly in the dose (10 uM) of granulosa cells from women submitted to in vitro fertilization. Perhaps this fact is important for adequate follicular growth, avoiding excessive growth, which could turn the follicle into cyst, making ovulation difficult.Keywords: Melatonin; Granulosa cells; Women; Marital infertility; In vitro fertilization

Melatonin supplementation in the management of obesity and obesity-associated disorders: a review of physiological mechanisms and clinical applications

Despite the evolving advances in clinical approaches to obesity and its inherent comorbidities, the therapeutic challenge persists. Among several pharmacological tools already investigated, recent studies suggest that melatonin supplementation could be an efficient therapeutic approach in the context of obesity. In the present review, we have amalgamated the evidence so far available on physiological effects of melatonin supplementation in obesity therapies, addressing its effects upon neuroendocrine systems, cardiometabolic biomarkers and body composition. Most studies herein appraised employed melatonin supplementation at dosages ranging from 1 to 20 mg/day, and most studies followed up participants for periods from 3 weeks to 12 months. Overall, it was observed that melatonin plays an important role in glycaemic homeostasis, in addition to modulation of white adipose tissue activity and lipid metabolism, and mitochondrial activity. Additionally, melatonin increases brown adipose tissue volume and activity, and its antioxidant and anti-inflammatory properties have also been demonstrated. There appears to be a role for melatonin in adiposity reduction; however, several questions remain unanswered, for example melatonin baseline levels in obesity, and whether any seeming hypomelatonaemia or melatonin irresponsiveness could be clarifying factors. Supplementation dosage studies and more thorough clinical trials are needed to ascertain not only the relevance of such findings but also the efficacy of melatonin supplementation

Retroviral transfer of the p16INK4a cDNA inhibits C6 glioma formation in Wistar rats

BACKGROUND: The p16(INK4A) gene product halts cell proliferation by preventing phosphorylation of the Rb protein. The p16INK4a gene is often deleted in human glioblastoma multiforme, contributing to unchecked Rb phosphorylation and rapid cell division. We show here that transduction of the human p16INK4a cDNA using the pCL retroviral system is an efficient means of stopping the proliferation of the rat-derrived glioma cell line, C6, both in tissue culture and in an animal model. C6 cells were transduced with pCL retrovirus encoding the p16INK4a, p53, or Rb genes. These cells were analyzed by a colony formation assay. Expression of p16INK4a was confirmed by immunohistochemistry and Western blot analysis. The altered morphology of the p16-expressing cells was further characterized by the senescence-associated β-galactosidase assay. C6 cells infected ex vivo were implanted by stereotaxic injection in order to assess tumor formation. RESULTS: The p16INK4a gene arrested C6 cells more efficiently than either p53 or Rb. Continued studies with the p16INK4a gene revealed that a large portion of infected cells expressed the p16INK4a protein and the morphology of these cells was altered. The enlarged, flat, and bi-polar shape indicated a senescence-like state, confirmed by the senescence-associated β-galactosidase assay. The animal model revealed that cells infected with the pCLp16 virus did not form tumors. CONCLUSION: Our results show that retrovirus mediated transfer of p16INK4a halts glioma formation in a rat model. These results corroborate the idea that retrovirus-mediated transfer of the p16INK4a gene may be an effective means to arrest human glioma and glioblastoma

Imprinting.

Imprinting is a type of learning by which an animal restricts its social preferences to an object after exposure to that object. Filial imprinting occurs shortly after birth or hatching and sexual imprinting, around the onset of sexual maturity; both have sensitive periods. This review is concerned mainly with filial imprinting. Filial imprinting in the domestic chick is an effective experimental system for investigating mechanisms underlying learning and memory. Extensive evidence implicates a restricted part of the chick forebrain, the intermediate and medial mesopallium (IMM), as a memory store for visual imprinting. After imprinting to a visual stimulus, neuronal responsiveness in IMM is specifically biased toward the imprinting stimulus. Both this bias and the strength of imprinting measured behaviorally depend on uninterrupted sleep shortly after training. When learning-related changes in IMM are lateralized they occur predominantly or completely on the left side. Ablation experiments indicate that the left IMM is responsible for long-term storage of information about the imprinting stimulus; the right side is also a store but additionally is necessary for extra storage outside IMM, in a region necessary for flexible use of information acquired through imprinting. Auditory imprinting gives rise to biochemical, neuroanatomical, and electrophysiological changes in the medio-rostral nidopallium/mesopallium, anterior to IMM. Auditory imprinting has not been shown to produce learning-related changes in IMM. Imprinting may be facilitated by predispositions. Similar predispositions for faces and biological motion occur in domestic chicks and human infants. WIREs Cogn Sci 2013, 4:375-390. doi: 10.1002/wcs.1231 For further resources related to this article, please visit the WIREs website.This review is written in memory of the late Sir Gabriel Horn, in recognition of his pioneering work on the neurobiology of imprinting. I am indebted to Robert Levin, Alister Nicol, Revaz Solomonia, Rie Suge, and two anonymous referees for valuable comments on a draft manuscript. The review was written while in receipt of a project grant from the Biotechnology and Biological Sciences Research Council.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/wcs.123

Aspectos cronobiológicos na enxaqueca episódica e crônica

Altered melatonin secretion and circadian, seasonal variations have been shown in migraine patients, but little is known about migraine chronobiological features. Two hundred migraine patients were studied. Headaches were reported to occur after changes in patients sleep schedule (46%), shift work (86%) and traveling across time zones (79%). Patients significantly delayed their sleep phase, 54% shifted their sleep phase. Chronobiology is a relevant aspect in migraine patients.Secreção alterada de melatonina e as variações sazonais têm sido demonstrado em pacientes com enxaqueca, mas pouco é sabido sobre as características cronobiológicas na enxaqueca. Duzentos pacientes com enxaqueca foram estudados. Dores de cabeça foram relatadas ocorrer após as alterações do horário do sono em pacientes (46%), trabalho por turnos trocados (86%) e viajar através dos fusos horários (79%). Pacientes atrasaram significativamente a fase do sono, 54% alteraram a fase de sono. Cronobiologia é um aspecto relevante em pacientes com enxaqueca

Circadian system coordination: new perspectives beyond classical models

BackgroundThis review examines novel interaction mechanisms contributing to the robustness of circadian rhythms, focusing on enhanced communication between the suprachiasmatic nucleus (SCN) and peripheral clocks. While classical models explain biological clocks through molecular interactions and biochemical signaling, they incompletely account for several key features: precision maintenance despite cellular noise, rapid system-wide synchronization, and temperature compensation. We propose that the SCN, acting as a central hub, may utilize non-classical mechanisms to maintain robust synchronization of peripheral clocks, contributing to biological timekeeping stability. The clinical implications of this model are significant, potentially offering new approaches for treating circadian-related disorders through quantum-based interventions. Recent advances in quantum biosensors and diagnostic tools show promise for early detection and monitoring of circadian disruptions, while quantum-based therapeutic strategies may provide novel treatments for conditions ranging from sleep disorders to metabolic syndromes.Aim of reviewTo evaluate classical models of circadian rhythm robustness and propose a novel synchronization model incorporating quantum mechanical principles, supported by recent advances in quantum biology and chronobiology, with emphasis on potential clinical applications.Key scientific conceptsRecent research in quantum biology suggests potential mechanisms for enhanced circadian system coordination. The proposed model explores how quantum effects, including entanglement and coherence, may facilitate rapid system-wide synchronization and temporal coherence across tissues. These mechanisms could explain features not fully addressed by classical models: precision maintenance in noisy cellular environments, rapid resynchronization following environmental changes, temperature compensation of circadian periods, and sensitivity to weak electromagnetic fields. The framework integrates established chronobiology with quantum biological principles to explain system-wide temporal coordination and suggests new therapeutic approaches for circadian-related disorders