Journal of Pineal Research最新文献

Postmenopausal women have a significantly increased risk of cardiovascular disease and osteoporosis due to the lack of estrogen protection. To explore the effects of melatonin on clock genes and glucose and lipid metabolic disorders of postmenopausal women, the models of ovariectomized (OVX) mice under different dietary conditions were generated and given melatonin gavage for 8 weeks. Biochemical indexes of serum and the morphology and histology of livers of the mice were checked. Transcriptome analysis, qPCR and Western blot were used to detect the expressional levels of genes related to clock and glucose and lipid metabolism in the livers of mice. The intestinal microbiota of the ovariectomized mice under different dietary conditions was further analyzed with 16S rDNA sequences. Melatonin significantly reduced the high concentrations of TC and LDL-C in the serum and lipid accumulation in the livers of the ovariectomized mice, and downregulated the protein expression associated with cholesterol and fatty acid biosynthesis, including HMGCR, FDPS, IDI1, MVK, LSS, FASN, and ACC. Melatonin could also improve the insulin resistance of the ovariectomized mice, upregulate the protein expression levels of p-IRS1, p-AKT, and p-mTOR, and reduce the protein expression level of p-Glycogen Synthase under high-fat diet (HFD) conditions. In addition, melatonin restored the clock genes expression disturbances caused by ovarian removal or high-fat diets, and upregulated the expression of the core circadian clock genes Clock and Bmal1. Melatonin also effectively increased the abundance of beneficial bacteria, improved the structure of microflora, and reduced the harmful bacteria of the ovariectomized mice fed with HFD. These results suggest that melatonin could affect liver clock genes expression and gut microbiota in ovariectomized mice, and improve glucose and lipid metabolic disorders under different dietary conditions.

In this letter to the editor, we comment on the recently published study from Scott et al. (2025), which highlights circadian misalignment as a possible determinant of insomnia severity. Considering the robust methodology of this study and in light of recent research aiming at optimizing melatonin treatment schedules, our letter explores why these findings may pave the way towards an extension of current recommendations for melatonin administration in insomnia, while encouraging the quantification of circadian misalignment during sleep medicine clinical practice. Finally, possible methodologies to routinely assess circadian misalignment in insomnia patients are discussed.

Evidence exists for the daily rhythmicity of bone metabolism that may be influenced by melatonin production, reproductive hormones, the light/dark cycle, or all three, but the ability to determine their independent contributions is confounded by the synchrony of the sleep/wake and dark/light cycles with the endogenous circadian system in sighted individuals. Blind participants, who often have no circadian light perception and may exhibit desynchrony between their sleep/wake cycle and circadian system, provide an opportunity to study the independent contribution of melatonin and light on bone metabolism in a field-based setting. In this exploratory study, 35 pre-, peri-, and postmenopausal blind women (N = 13, 8, and 14, respectively) both with (N = 17) and without (N = 18) visual light perception (LP and NPL, respectively) who were either normally entrained (N = 19) or abnormally entrained or non-entrained (N = 16) to the 24-h day were randomly selected from a cohort of 130 visually impaired women. Levels of 6-sulfatoxymelatonin (aMT6s; ng/h) and the bone resorption marker amino-terminal cross-linked telopeptide of collagen I (NTx; BCE nM/h) were assayed from serial urine samples collected over 48 h and fit by a cosinor model to determine the presence of significant 24-h rhythms. Most blind women (N = 32/35, 91%) had a significant 24-h aMT6s rhythm (mean ± SD, 03:44 ± 4:27 hh:mm), but fewer women had a significant 24-h NTx rhythm (N = 20/35, 57%; 21:01 ± 5:50 hh:mm). There was no significant difference in the proportion of women with significant NTx rhythms by visual light perception status (LP: N = 10/17, 59% vs. NPL, N = 10/18, 56%), entrainment status (Entrained: N = 11/19, 58% vs. Abnormal or Not entrained: N = 9/16, 56%) or reproductive status (Premenopausal: N = 7/13, 54% vs. Perimenopausal: 5/8, 63% vs. Postmenopausal: 8/14, 57%). There was no correlation between the peak timings of aMT6s and NTx among the 17 participants with significant rhythms in both metabolites (r = 0.07, p = 0.80). NTx area under the curve was significantly higher among perimenopausal women with LP (p = 0.04). Our results do not support a direct influence of light, melatonin, or reproductive status on NTx rhythms, but the apparent increase of NTx in the perimenopausal period warrants further investigation.

Parkinson's disease is the second most frequent neurodegenerative disease after Alzheimer's disease, and the most common neurodegenerative disease that causes movement dysfunction. Without innovations in prevention and treatment, the incidence and prevalence of Parkinson's disease is projected to increase by > 30% by 2030, making the development of new treatments an urgent priority. We previously investigated the association between melatonin receptor agonists and Parkinson's disease using the US Food and Drug Administration's Adverse Event Reporting System (FAERS). The results showed that ramelteon may reduce the incidence of Parkinson's disease. However, since the US FAERS relies on spontaneous reports, which are susceptible to reporting bias, further validation using real-world data is required. This study investigated the association between ramelteon use and risk of developing Parkinson's disease using the DeSC database, a Japanese claims database reported to be representative of the general Japanese population. The association was evaluated using sequence symmetry analysis, with the adjusted sequence ratio (ASR) serving as the evaluation index. Our DeSC database analysis showed a negative association between ramelteon use and Parkinson's disease (ASR: 0.959, 95% confidence interval: 0.955–0.964). Our results support previous reports suggesting that ramelteon may help suppress the onset of Parkinson's disease. However, even though this study used real-world data, these results should be interpreted with caution, as a sequence symmetry analysis cannot be adjusted for covariates. Therefore, additional pharmacoepidemiological studies are needed to further verify the potential risk of Parkinson's disease associated with ramelteon use.

The association between modern lifestyle factors and dry eye disease (DED) pathogenesis has garnered increasing scientific attention. Emerging evidence implicates circadian disruption—a prevalent consequence of contemporary living patterns—as a significant yet not fully clarified pathogenic factor in DED development. To address this knowledge gap, we developed a circadian disruption mouse model using chronic jet lag exposure. Mice subjected to chronic jet lag exhibited conjunctival clock gene dysregulation and upregulated pro-inflammatory mediators, such as TNF-α, IL-6, and IL-17. Transcriptomic profiling demonstrated marked activation of IL-17-mediated inflammatory pathways within the conjunctival tissue. Therapeutic IL-17 neutralization substantially attenuated ocular surface inflammation, improved corneal epithelial integrity, and decreased apoptotic cell density in circadian disruption-induced dry eye mouse model. Moreover, REV-ERBα agonism potently suppressed IL-17 transcription, whereas BMAL1 deficiency exacerbated IL-17-driven inflammatory responses through REV-ERBα downregulation. Chronic jet lag additionally induced ocular surface microbiota dysbiosis, characterized by Firmicutes overproliferation. Melatonin administration effectively suppressed conjunctival IL-17 expression through BMAL1-REV-ERBα pathway activation while reducing the relative abundance of Firmicutes to restore ocular surface microbiota balance. Our study reveals that circadian disruption induces ocular surface inflammation through the BMAL1-REV-ERBα-IL-17 signaling axis and exacerbates dysbiosis of the ocular surface microbiota. Melatonin mitigates these pathological alterations via dual-directional modulation of circadian-immune signaling crosstalk and restoration of microbiota balance. Importantly, this study establishes melatonin as a multifaceted therapeutic agent for combating lifestyle-associated DED, while elucidating the underlying mechanisms governing circadian rhythm-microbiome axis dynamics in ocular surface pathogenesis.