RESUMO

Bipolar disorder (BD) is a neuropsychiatric illness characterized by recurrent episodes of mania and depression, leading to profound cognitive and functional impairments, psychiatric and metabolic comorbidities, and substantial healthcare costs. Due to its complex nature and absence of specific biomarkers, BD presents significant daily challenges for clinicians. Therefore, advancing our understanding of BD pathophysiology is essential to identify novel diagnostic biomarkers and potential therapeutic targets. Although its neurobiology remains unclear, disruption of circadian rhythms and lipid alterations have emerged as key hallmarks of BD. As essential components of the brain, lipids play a pivotal role in regulating synaptic activity and neuronal development. Thus, alterations in brain lipids may contribute to the neuroanatomical changes and reduced neuroplasticity observed in BD. The levels of toxic lipids inside the cell are buffered by lipid droplets that regulate the storage of neutral lipids. These dynamic organelles adapt to cellular needs, and their dysregulated accumulation has been linked to various pathological conditions. Notably, lipid droplets and various lipid classes display rhythmic oscillations throughout the 24-hour cycle, suggesting a link between lipid metabolism, circadian rhythms and lipid droplets. In this review, we explore the impairment of circadian rhythms and lipid metabolism in BD, along with evidence demonstrating that circadian clocks regulate the accumulation of lipid droplets. Importantly, we propose the "lipid droplets hypothesis for BD" that considers that the compromised lipid metabolism in BD is intimately associated with alterations in the lipid droplets homeostasis, which can be driven by disturbances in the circadian clocks.

RESUMO

Driven by autonomous molecular clocks that are synchronized by a master pacemaker in the suprachiasmatic nucleus, cardiac physiology fluctuates in diurnal rhythms that can be partly or entirely circadian. Cardiac contractility, metabolism, and electrophysiology, all have diurnal rhythms, as does the neurohumoral control of cardiac and kidney function. In this review, we discuss the evidence that circadian biology regulates cardiac function, how molecular clocks may relate to the pathogenesis of heart failure, and how chronotherapeutics might be applied in heart failure. Disrupting molecular clocks can lead to heart failure in animal models, and the myocardial response to injury seems to be conditioned by the time of day. Human studies are consistent with these findings, and they implicate the clock and circadian rhythms in the pathogenesis of heart failure. Certain circadian rhythms are maintained in patients with heart failure, a factor that can guide optimal timing of therapy. Pharmacologic and nonpharmacologic manipulation of circadian rhythms and molecular clocks show promise in the prevention and treatment of heart failure.

Assuntos

RESUMO

ABSTRACT Acute retinal pigment epitheliitis (ARPE) is an idiopathic, self-limiting inflammatory retinal disorder that particularly affects healthy young individuals. The characteristic fundoscopic appearance of the acute retinal pigment epitheliitis includes a fine pigment stippling surrounded by a yellow-white hypopigmented halos in the macula. Although the exact pathogenesis of the disease remains unknown, some reports have suggested a relationship between a viral infection and acute retinal pigment epitheliitis. Acute retinal pigment epitheliitis is a rare disorder, and only single case reports or case series are found in the literature. The clinical and demographic characteristics of patients with this disease are not fully understood because of its rarity. In this study, we searched the literature to collect clinical and demographic features of the reported cases. We detail the characteristics of acute retinal pigment epitheliitis were pointed and discuss the pathogenesis of the disease.(AU)

RESUMO A epitelite pigmentar retiniana aguda (EPRA) é uma doença inflamatória idiopática e autolimitada da retina, que afeta especialmente indivíduos jovens e saudáveis. À fundoscopia, a aparência característica dessa entidade é de um pontilhado fino do pigmento, cercado de halos hiperpigmentados branco-amarelados na mácula. A patogênese exata da doença ainda é desconhecida, mas alguns relatos apontam uma relação entre epitelite pigmentar retiniana aguda e infecções virais. A epitelite pigmentar retiniana aguda é uma condição rara e na literatura há apenas relatos de casos individuais ou séries de casos. As características clínicas e demográficas da doença não são totalmente compreendidas, devido à sua raridade. Para este relato, foi feita uma busca na literatura para coletar os dados clínicos e demográficos dos casos relatados. Finalmente, são apontadas as características da epitelite pigmentar retiniana aguda e discute-se a patogênese da doença.(AU)

Assuntos

RESUMO

Circadian rhythms orchestrate crucial physiological functions and behavioral aspects around a day in almost all living forms. The circadian clock is a time tracking system that permits organisms to predict and anticipate periodic environmental fluctuations. The circadian system is hierarchically organized, and a master pacemaker located in the brain synchronizes subsidiary clocks in the rest of the organism. Adequate synchrony between central and peripheral clocks ensures fitness and potentiates a healthy state. Conversely, disruption of circadian rhythmicity is associated with metabolic diseases, psychiatric disorders, or cancer, amongst other pathologies. Remarkably, the molecular machinery directing circadian rhythms consists of an intricate network of feedback loops in transcription and translation which impose 24-h cycles in gene expression across all tissues. Interestingly, the molecular clock collaborates with multitude of epigenetic remodelers to fine tune transcriptional rhythms in a tissue-specific manner. Very exciting research demonstrate that three-dimensional properties of the genome have a regulatory role on circadian transcriptional rhythmicity, from bacteria to mammals. Unexpectedly, highly dynamic long-range chromatin interactions have been revealed during the circadian cycle in mammalian cells, where thousands of regulatory elements physically interact with promoter regions every 24 h. Molecular mechanisms directing circadian dynamics on chromatin folding are emerging, and the coordinated action between the core clock and epigenetic remodelers appears to be essential for these movements. These evidences reveal a critical epigenetic regulatory layer for circadian rhythms and pave the way to uncover molecular mechanisms triggering pathological states associated to circadian misalignment.

Assuntos

RESUMO

Objective: To assess sleep bruxism prevalence and its association with circadian preference and sleep-related characteristics among dental students. Methods: Dental students of the Federal University of Minas Gerais participated in this cross-sectional study. Participants answered a scale assessing individuals' circadian preference, and a questionnaire regarding sleep-related characteristics and behaviors, history of muscle ache in the temporomandibular area, and history of bruxism. Results: One hundred fifty-two students participated in the study. Sleep bruxism was reported by 11.3%. Most students (63.2%) were classified as intermediary, 34.9% as morningness, and 1.3% as eveningness. Individuals who reported muscle ache in the temporomandibular area in the morning (PR = 3.5; 95% CI = 1.1-11.5) were more likely to be in the group with sleep bruxism. Conclusion: Muscle ache in the temporomandibular area is an important associated factor with sleep bruxism among dental students. Special attention should be paid to dental students' circadian preference.

Assuntos

RESUMO

Myocardial gene expression and metabolism fluctuate over the course of the day in association with changes in energy supply and demand. Time-of-day-dependent oscillations in myocardial processes have been linked to the intrinsic cardiomyocyte circadian clock. Triiodothyronine (T3) is an important modulator of heart metabolism and function. Recently, our group has reported time-of-day-dependent rhythms in cardiac T3 sensitivity, as well as, T3-mediated acute alterations on core clock components. Hypo and hyperthyroidism are the second most prevalent endocrine disease worldwide. Considering the importance of the cardiomyocyte circadian clock and T3 to cardiac physiology, the aim of this study was to investigate the consequences of chronic hypo and hyperthyroidism on 24-h rhythms of circadian clock genes in the heart. Hypo and hyperthyroidism was induced in rats by thyroidectomy (Tx) and i.p. injections of supraphysiological dose of T3, respectively. Here we report alterations in mRNA levels of the major core clock components (Bmal1, Per2, Nr1d1, and Rora) for both experimental conditions (with the exception of Per2 during hyperthyroid condition). Oscillations in mRNA levels of key glucose and fatty-acid metabolism genes known to be clock controlled (Pdk4, Ucp3, Acot1, and Cd36) were equally affected by the experimental conditions, especially during the hypothyroid state. These findings suggest that chronic alterations in thyroid status significantly impacts 24-h rhythms in circadian clock and metabolic genes in the heart. Whether these perturbations contribute toward the pathogenesis of cardiac dysfunction associated with hypo and hyperthyroidism requires further elucidation.

Assuntos

RESUMO

Neurospora crassa is a model organism for the study of circadian clocks, molecular machineries that confer ∼24-hr rhythms to different processes at the cellular and organismal levels. The FREQUENCY (FRQ) protein is a central component of the Neurospora core clock, a transcription/translation negative feedback loop that controls genome-wide rhythmic gene expression. A genetic screen aimed at determining new components involved in the latter process identified regulation of conidiation 1 (rco-1), the ortholog of the Saccharomyces cerevisiae Tup1 corepressor, as affecting period length. By employing bioluminescent transcriptional and translational fusion reporters, we evaluated frq and FRQ expression levels in the rco-1 mutant background observing that, in contrast to prior reports, frq and FRQ expression are robustly rhythmic in the absence of RCO-1, although both amplitude and period length of the core clock are affected. Moreover, we detected a defect in metabolic compensation, such that high-glucose concentrations in the medium result in a significant decrease in period when RCO-1 is absent. Proteins physically interacting with RCO-1 were identified through co-immunoprecipitation and mass spectrometry; these include several components involved in chromatin remodeling and transcription, some of which, when absent, lead to a slight change in period. In the aggregate, these results indicate a dual role for RCO-1: although it is not essential for core-clock function, it regulates proper period and amplitude of core-clock dynamics and is also required for the rhythmic regulation of several clock-controlled genes.

Assuntos