Circadian Rhythm Dysregulation and Restoration: The Role of Melatonin

Sleep is an essential component of overall human health but is so tightly regulated that when disrupted can cause or worsen certain ailments. An important part of this process is the presence of the well-known hormone, melatonin. This compound assists in the governing of sleep and circadian rhythms. Previous studies have postulated that dysregulation of melatonin rhythms is the driving force behind sleep and circadian disorders. A computer-aided search spanning the years of 2015–2020 using the search terms melatonin, circadian rhythm, disorder yielded 52 full text articles that were analyzed. We explored the mechanisms behind melatonin dysregulation and how it affects various disorders. Additionally, we examined associated therapeutic treatments including bright light therapy (BLT) and exogenous forms of melatonin. We found that over the past 5 years, melatonin has not been widely investigated in clinical studies thus there remains large gaps in its potential utilization as a therapy.

Gut Microbiota Mediates Oolong Tea Polyphenols Alleviation of Circadian Rhythm Disturbance

BackgroundTea polyphenols can be digested in the intestinal tract so as to promote the growth of helpful gut microbiota, and through the production of catechin, tryptophan, acetic acid and other active substances which involved in the modulation of circadian rhythms mechanism to improve the circadian rhythm disorders and neurological weakness, while its specific mechanism is still unclear. The interaction between host circadian rhythm and gut microbes through the gut-brain axis (GBA) provides new clues for tea polyphenols to improve host health. Our present research mainly investigated the metabolites of the gut microbiota and the heterogeneous expression of circadian rhythm genes in the liver and hypothalamic, and then revealed the modulatory role of oolong tea polyphenols (OTP) of circadian rhythm disorder via the GBA. We used 16S rDNA and untargeted metabolomics sequencing techniques to analyze the effects of OTP on intestinal flora diversity and abundance of specific flora in mice with diurnal disorders, and to screen out marker metabolites which may be involved in circadian rhythm regulation. Transcriptomics and 10X single-cell sequencing were used to evaluate the effects of OTP on circadian rhythm genes in liver and hypothalamus and hypothalamus cell types in mice with diurnal disorders. The Y maze and Morris water maze experiments were investigated the effects of OTP on long-term and short-term memory impairment.ResultsBy establishing a circadian rhythm disorder mouse model, our experimental results showed that OTP improved the structural disorder of the intestinal microbiota caused by continuous darkness, especially significantly decreased the ratio of Firmicutes/Bacteroidetes (F/B), thereby modulating the production of metabolites related to pyruvate metabolism, glycolysis/gluconeogenesis, and tryptophan metabolism to alleviate the steady-state imbalance caused by circadian rhythm disorders. In addition, OTP can significantly ameliorate the rhythm oscillation disorder of specific gut microbes and liver clock genes induced by continuous darkness, and made dysrhythmic mice perform well in cognitive behavior tests. Simultaneously, OTP intervention increased the number of rhythmic expression genes in the liver which in the CD group has 156, while in the OTP group has 208. Transplanting fecal microbiota from the OTP group into germ-free mice exhibited that OTP significantly increased the number of hypothalamus cell clusters, up-regulated the number of astrocytes and fibroblasts, and enhanced the expression of circadian rhythm genes Cry2, Per3, Bhlhe41, Nr1d1, Nr1d2, Dbp, and Rorb in hypothalamic cells. ConclusionsOur results confirmed that OTP reduced the F/B ratio, made the daily oscillation of the intestinal microbiota tended to be regular, actively improve the intestinal microecological status, the content of important metabolite closely associated with circadian rhythm such as Tryptophan, Glutamine, 2-indolecarboxylic acid and some others has been significantly increased, the poor expression of clock genes (such as Cry2, Per3, Bhlhe41, Nr1d1, Nr1d2, Dbp and Rorb) in liver and hypothalamus cells has been improved. These results indicated that OTP can significantly improve the metabolic imbalance and cognitive impairment caused by the circadian rhythm disorder, maintain the host's homeostasis, which with potential prebiotic functional characteristics to positively contribute to host health.

Insomnia and Its Related Factors in Elderly Population of Tehran, Iran

Background and Objective: The present study aimed to determine the prevalence of insomnia and its related factors among elderly population of Tehran, Iran. Materials and Methods: This study was a cross-sectional descriptive study. Data were collected by a three-part questionnaire. The first part included demographic information; the second part contained data on weight, height, neck circumference, menstruation status, diabetes, hypertension (HTN), and heart disease. The third part contained questions about Insomnia Screening Questionnaire (ISQ). Cluster sampling was used and 651 samples were selected for the present study. Results: The prevalence of insomnia was significantly higher in female, single, and illiterate subjects and also in subjects with chronic diseases, psychological disorders, circadian rhythm disorder, restless legs syndrome (RLS), parasomnia, and sleep apnea. Conclusion: According to this study, insomnia is common among elderly population of Tehran, and there is a relationship between this disorder and chronic diseases, psychological disorders, and sleep disorders.