Asociación entre calcificaciones de la glándula pineal y enfermedad aterosclerótica intracraneal en adultos mayores

Background: This study assesses whether pineal gland calcification (PGC) – a surrogate for reduced endogenous melatonin production – is associated with significant stenosis of large intracranial arteries – a biomarker of intracranial atherosclerotic disease (ICAD). Methods: Individuals aged ≥60 years enrolled in the Three Villages Study received head CT to assess PGC and MRA to estimate stenosis of large intracranial arteries. Multivariate logistic regression models were fitted to assess the association between PGC and ICAD, after adjusting for relevant confounders. Inverse probability of exposure weighting was used to estimate the effect of PGC on ICAD. Results: A total of 581 individuals were enrolled. PGC and ICAD were associated in a fully-adjusted logistic regression model (p=0.032). Inverse probability of exposure weighting showed an estimate for the proportion of ICAD among those without PGC of 3.7% and the adjusted-effect coefficient was 5.7% higher among those with PGC (p=0.031). Conclusions: PGC is associated with ICAD. Study results provide grounds for evaluating the role of melatonin deficiency in ICAD progression. Keywords: Pineal gland calcification, intracranial atherosclerosis, stenosis of large intracranial arteries, melatonin; population study, older adults

Transient Receptor Potential-Vanilloid (TRPV1-TRPV4) Channels in the Atlantic Salmon, Salmo salar. A Focus on the Pineal Gland and Melatonin Production

Fish are ectotherm, which rely on the external temperature to regulate their internal body temperature, although some may perform partial endothermy. Together with photoperiod, temperature oscillations, contribute to synchronizing the daily and seasonal variations of fish metabolism, physiology and behavior. Recent studies are shedding light on the mechanisms of temperature sensing and behavioral thermoregulation in fish. In particular, the role of some members of the transient receptor potential channels (TRP) is being gradually unraveled. The present study in the migratory Atlantic salmon, Salmo salar, aims at identifying the tissue distribution and abundance in mRNA corresponding to the TRP of the vanilloid subfamilies, TRPV1 and TRPV4, and at characterizing their putative role in the control of the temperature-dependent modulation of melatonin production—the time-keeping hormone—by the pineal gland. In Salmo salar, TRPV1 and TRPV4 mRNA tissue distribution appeared ubiquitous; mRNA abundance varied as a function of the month investigated. In situ hybridization and immunohistochemistry indicated specific labeling located in the photoreceptor cells of the pineal gland and the retina. Additionally, TRPV analogs modulated the production of melatonin by isolated pineal glands in culture. The TRPV1 agonist induced an inhibitory response at high concentrations, while evoking a bell-shaped response (stimulatory at low, and inhibitory at high, concentrations) when added with an antagonist. The TRPV4 agonist was stimulatory at the highest concentration used. Altogether, the present results agree with the known widespread distribution and role of TRPV1 and TRPV4 channels, and with published data on trout (Oncorhynchus mykiss), leading to suggest these channels mediate the effects of temperature on S. salar pineal melatonin production. We discuss their involvement in controlling the timing of daily and seasonal events in this migratory species, in the context of an increasing warming of water temperatures.

“Endogenous Melatonin Concentration Along with the Expression of Mitochondrial Regulator Genes is Elevated by the Serum Shock Process in the U87-MG Cell Line”

According to the World Health Organization, glioblastoma, also known as the fourth grade in the development of astrocytoma, is a glial tumor limited to the central nervous system with a strong ability to invade the brain parenchyma. Melatonin can be generated outside of the pineal gland tissue, according to new research. Melatonin is produced by mitochondria independently but in concert with cell demands, and it plays an important function in cell cycle and metabolism regulation. As a result, we set out to investigate the association between cell metabolism and the serum shock-induced increase in endogenous melatonin, as well as the percentage of cell proliferation.Background: Melatonin can be produced in the mitochondria organelle of glioblastoma cells without the involvement of the pineal gland, according to new research. Regarding the physiological function of melatonin secreted by the pineal gland in the regulation of rhythmicity, the goal of this study was to see if the glioblastoma cell's melatonin production ability could be influenced using a typical serum shock technique established for cellular rhythm regulator.Material and methods: First, U87-MG glioblastoma cells were cultured in a DMEM medium containing 10% FBS and then cells were treated with a standard serum shock process (no FBS, 8h). The concentration of melatonin was measured using ELISA method in supernatant and cell extracts of Shock and control groups. The cell proliferation was measured by using BrdU staining and flow cytometry assessment. The gene expression levels of some mitochondria or circadian related genes including TFAM, BMAL1, PPARGC1A(PGC1-α), and DNM1L(DRP1) were measured, using qRT-PCR method.Results: In comparison to the control group, serum shock treated U87-MG glioblastoma cells had higher concentrations of cellular and released endogenous melatonin (two times). At the mRNA level, we discovered considerable upregulation of mitochondrial or circadian regulator genes (TFAM, BMAL1, PPARGC1A, and DNM1L); in the shock group compared to the control group (P <0.0002). Furthermore, although the percentage of proliferative cells (Brdu positive) was higher in the shock group, it was not statistically significant.Conclusion: The serum shock procedure has a significant impact on the U87-MG cell line's cellular activity. In terms of the study's findings, it's worth noting that an increase in endogenous melatonin concentration influences several signaling pathways within the U87-MG cell line, as seen by the increased expression of candidate genes.In light of the findings of this study, it's worth noting that further research into the role of endogenous melatonin and its effects on cancer cells is critical, and that comparing the results of normal and cancer cells can reveal the hotspots of the signaling pathways involved, which could facilitate in better understanding the biology of glioblastoma.

The experience of successful use of melatonin, L‑arginine and L‑carnitine in treatment post-COVID‑19 pain syndromes in persons with cystic transformation of the pineal gland

As an introduction, the article presents a small review of the literature devoted to the problem of clinical variants of postovoid syndrome and, in particular, headaches and back pain. There are 6 cases with various headaches and 1 case with back pain in patients with cystic transformation of the pineal gland after a verified COVID-19 infection. All patients were diagnosed with melatonin, L‑arginine and L‑carnitine deficiency before treatment. After the replacement therapy, the pain syndrome was stopped in all patients within 10 days, and a month after the start of treatment, the indicators of melatonin, L‑arginine and l‑carnitine returned to the reference values of the norm.

Dynamics of Changes in the Indicators of Mathematical Analysis of Heart Rate in Conditions of Adrenaline Myocardial Dystrophy against the Background of Different Functional Activity of the Pineal Gland

The purpose of the study was to examine the features of heart rate variability in experimental hyper- and hypofunction of the pineal gland, complicated by adrenal myocardial dystrophy. Materials and methods. To solve the set tasks, three models of functional states were created: hypo-, hyperfunction of the pineal gland, adrenaline myocardial dystrophy. Hypermelatoninemia was reproduced by administering melatonin. The hypofunction of the pineal gland was simulated by round-the-clock lighting. An experimental model of cardiac pathology, namely adrenaline myocardial dystrophy, was reproduced by administering adrenaline hydrochloride. The degree of tension of regulatory mechanisms and mechanisms of nervous regulation was assessed by mathematical analysis of heart rate variability. Results and discussion. The task of mathematical analysis is to extract “hidden information” and thereby assess the state and degree of tension of the regulatory mechanisms of the whole organism. According to the authors, mathematical analysis allows a differentiated approach to the assessment of regulatory effects, which is done by the nervous autonomic system, subcortical structures and the cerebral cortex. The data obtained by the authors suggest that the introduction of adrenaline in conditions of hypofunction of the pineal gland have cause-and-effect changes. These changes lead to disorders of autonomic regulation and possibly a trigger mechanism for a decrease in melatonin production by the pineal gland. Studies have shown that one of the advantages in conditions of hyperfunction of the pineal gland is the dominant role of parasympathetic processes in the mechanisms of adaptation of the heart to conditions of adrenal myocardial dystrophy. Timely and sufficient activation of melatonin provides a high efficiency of compensatory-adaptive changes and a positive role in increasing myocardial resistance. Conclusion. The results of the study showed that the dynamics of changes in the values of the indicators of the mathematical analysis of the heart rate in adrenal myocardial dystrophy against the background of hypo- and hyperfunction of the pineal gland revealed unidirectional changes. These changes are manifested in a decrease in heart rate, stress index and vegetative balance indicator. Consequently, the results obtained suggest that the introduction of melatonin against the background of adrenal myocardial dystrophy has a general corrective effect on the restoration of the functional state of the heart. Based on the results, the authors consider it appropriate to continue the study of the influence of various stressors on the functional state of the heart in conditions of different physiological activity of the pineal gland

Dysfunctional Learning and Verbal Memory in Patients with Elevated Tau Protein Levels and Serum Recoverin Autoantibodies—Case Series and Review

Recoverin-antibody-related disease is currently restricted to late-onset ataxia and autoimmune retinopathy, which can be paraneoplastic or not. However, cognitive dysfunction associated with recoverin antibodies has not been reported so far in a homogeneous patient group. Our case series is dedicated to describing the novel phenotype of cognitive impairment associated with recoverin antibodies. We included five patients with cognitive impairment who presented serum recoverin autoantibodies detected by immunoblots in our case series investigation. We also analyzed their psychopathology, clinical data, cerebrospinal fluid (CSF), and neuroimaging data. Five patients with cognitive impairment associated with serum recoverin antibodies exhibited profound dysfunctional learning and verbal memory. In the CSF of 40% of them, we also diagnosed axonal neurodegeneration entailing elevated tau and phosphorylated tau protein levels. Psychopathologies such as affective symptoms (restlessness, depressive mood, anxiety, complaintiveness) and formal thought disorder, such as rumination, were detected in 25–75% of the patients. We hypothesized a role of recoverin autoimmunity in the pineal gland involving consecutive modulation of hippocampus-based memory caused by an altered release of melatonin. We describe a novel phenotype of possible recoverin autoimmunity in patients with cognitive impairment. However, no clear diagnostic clues can be extracted because of the low diagnostic validity of the testing strategies applied. The possibility of recoverin antibody autoimmunity in the pineal gland correlating with a modulation of hippocampus-based memory should be further investigated.

CircRNA-WNK2 acts as a ceRNA for miR-328a-3p to promote AANAT expression in the male rat pineal gland

Noncoding RNAs (ncRNAs), including miRNAs and circRNAs, which are expressed with a daily rhythm in the rat pineal gland, are associated with the regulation of melatonin secretion and other biological functions. However, the mechanisms of these molecules in the rat pineal gland are not yet fully understood. In this study, we found circR-WNK2 was highly expressed at night, which may be involved in the regulation of melatonin secretion through the ceRNA mechanism. By dual luciferase reporter, RNA pulldown, and FISH assays, we found that miR-328a-3p can target circR-WNK2 and the Aa-nat mRNA 3’UTR. Transfection experiments indicated that circR-WNK2 could competitively bind to miR-328a-3p, reduce miR-328a-3p expression, and promote Aa-nat gene expression and melatonin secretion. And by constructing an SCGx rat model, we found that ncRNAs expressed in the pineal gland was regulated by signals from the SCN. This finding supports the hypothesis that these noncoding RNAs may interact to shape the circadian rhythm through transcriptional processing in melatonin synthesis.

Relationship between pineal gland, sleep and melatonin in fibromyalgia women: a magnetic resonance imaging study

A total of 80% of fibromyalgia (FM) population have reported poor sleep. In this regard, the pineal gland, involved in circadian rhythm processes as a key neuroendocrine organ which mainly synthesises and secretes melatonin, has never been studied before in this population. Therefore, this study aimed to evaluate the parenchyma pineal volume and its relation to sleep hours, sleep quality index and melatonin level at night. A total of 50 participants, 30 women with FM and 20 healthy control women underwent cranial magnetic resonance imaging. The total pineal volume, cyst pineal volume and parenchyma pineal volume were manually calculated in cubic millimetres. Also, the total pineal volume was estimated using Hasehawa method. Parenchyma pineal volume was significantly correlated with sleep hours (p-value = 0.041) and nocturnal melatonin level (p-value = 0.027). Moreover, there was also a non-significant correlation between parenchyma pineal volume and sleep quality index (p-value = 0.055). Furthermore, a mean parenchyma pineal volume of 102.00 (41.46) mm³ was observed, with a prevalence of 29.60% cyst in FM group. This is the first study that has reported pineal gland volumes, cyst prevalence and correlative relationships between parenchyma pineal volume and sleep hours and melatonin levels in women with FM.