Impact of Human Melanopsin Gene (OPN4) Polymorphisms (I394T, P10L) on Nocturnal Melatonin and Daily Rhythms in Young Adults

CLOCK rs1801260 and MTNR1B rs10830963 Polymorphisms Modulate the Association between Cholesterol Levels and Circadian Rhythms in Arctic Residents

Melanopsin gene polymorphism and volumetric change in the left hippocampal dentate gyrus following light therapy in mood disorders: An exploratory study

Introduction Bright light therapy (BLT) is an effective treatment for mood disorders. We previously reported that four weeks of bright light (BL) exposure in patients with mood disorders led to increased volume of the left dentate gyrus (DG). We propose a novel hypothesis that the extent of light-induced volumetric increase in the left DG may be influenced by individual genetic variation in the OPN4 gene, especially rs1079610. This exploratory study aimed to test this hypothesis. Methods We recontacted 21 patients with mood disorders who had previously participated in a 4-week, randomized controlled trial comparing BL (10,000 lux) and dim light (DL; 50 lux). All participants underwent magnetic resonance imaging and 18F-fluorodeoxyglucose (FDG) positron emission tomography at baseline and after 4 weeks of light exposure. Blood samples were collected for genotyping of two Single-Nucleotide Polymorphisms (SNPs) in OPN4 (rs1079610 and rs2675703), which are expressed in intrinsically photosensitive retinal ganglion cells. The primary outcome was the main effect of the rs1079610 genotype for percentage change volume (%ΔV) of the left DG. Analysis of covariance was conducted using a general linear model. Results The final sample size was 21 (BL group, n = 11; DL group, n = 10). A significant main effect of rs1079610 genotype (C allele carriers versus TT) was observed (F (1,17) = 7.16, P = 0.016, partial η2 = 0.3). Sensitivity analyses were performed with sequential adjustment for potential confounders. The association between rs1079610 genotype and %ΔV of the left DG remained statistically significant after adjustment for age, sex, baseline left DG volume, and diagnosis (F (1,13) = 4.8, P = 0.047, partial η2 = 0.27). Discussion The findings of this study suggest that rs1079610 in OPN4 might be a potential SNP that affects volumetric change in the left DG following light therapy in mood disorders.

Dopamine Receptor D2 gene Polymorphisms rs2005313, rs4274224, and rs4938019 in Pakistani Patients with Schizophrenia:a Diagnostic Tool for Schizophrenia

Shank3 mutation disrupts the molecular signature of sleepiness across development

Background Sleep problems are common in autism, emerge early in life and reduce quality of life, yet the mechanistic link between autism and poor sleep remains unclear. Human and rodent data indicate that difficulty falling asleep is a core feature of autistic insomnia, pointing to impaired responses to sleepiness as the underlying cause. We previously showed that adult mice carrying a mutation in the high-confidence autism gene Shank3 (Shank3ΔC) recapitulate this insomnia phenotype and struggle to respond to sleepiness after acute sleep deprivation. Here, we used Shank3ΔC mice to examine the molecular basis of sleepiness and how this autism-associated mutation alters it to inform understanding of sleep problems in autistic individuals. Methods This study used RNA-sequencing and bioinformatics to identify molecular targets underlying the effect of the Shank3ΔC mutation on the molecular basis of sleepiness across development in male mice. We first compared cortical genome-wide gene expression following acute sleep deprivation and recovery sleep in adult wild-type (WT) and mutant mice. We then used polysomnography and RNA-sequencing to assess the response to increased sleepiness in WT and mutant mice at postnatal days 24 and 30. Results The neurotypical response to acute sleep deprivation shifted from upregulating neuronal growth and development pathways at P24/P30 to upregulating DNA damage repair and neuronal activity-dependent transcription in adulthood. The Shank3ΔC mutation largely blocked recruitment of these pathways at P24 and in adulthood while paradoxically increasing the magnitude of the mutant response at P30. In addition, mutants consistently upregulated oxidative stress pathways linked to neurodegeneration and protein synthesis regardless of age, whereas WT animals downregulated these functions. Limitations This study examined gene expression only in male mice, used a single autism rodent model, and averaged signals across mixed cortical cell types. Future work should include females, additional autism models, and single-cell approaches in additional brain regions to further characterize the cellular effects of sleep deprivation and autism-associated mutations. Conclusions The Shank3ΔC mutation impairs the molecular accumulation of and response to sleepiness, both by elevating oxidative stress responses and by blocking the age-typical upregulation of pathways that differ between juveniles and adults.

Circadian Disruption Is Associated with Elevated Whole-Semen mtDNA Copy Number and Implicates CRY1 as a Candidate Regulator in Humans and Mice

Circadian disruption has been linked to impaired male fecundity, but its association with semen molecular phenotypes and circadian genes remains unclear. We analyzed 441 men from the Male Reproductive Health in Chongqing College Students cohort to assess whether social jetlag, an indicator of circadian disruption, was associated with whole-semen mitochondrial DNA copy number (mtDNAcn), an emerging biomarker of male fecundity. Core circadian genes related to mtDNAcn were screened using genetic polymorphism data. A light-cycle phase-shifting mouse model, Cry1-knockout mice, and testicular Cry1 re-expression models were used for experimental validation, with histology, transcriptomics, single-cell data, and proteomics analyses used to explore mechanisms. Social jetlag was associated with higher mtDNAcn in men (1.29-fold, p = 0.026), with a concordant increase in circadian-disrupted mice (1.33-fold, p = 0.010). Among core circadian genes, CRY1 showed the strongest association with mtDNAcn (p = 0.048). Cry1 knockout elevated mtDNAcn (2.18-fold, p < 0.001), whereas testicular Cry1 re-expression reduced it toward wild-type levels. Circadian disruption and Cry1 deficiency were accompanied by seminiferous epithelial disorganization, spermatogenesis-related transcriptomic changes, and altered mitochondrial pathway signatures. To our knowledge, this study is the first to identify whole-semen mtDNAcn as a circadian-disruption-associated molecular phenotype and supports CRY1 as a candidate regulator.

THE SIGNIFICANCE OF THE NOS3 G894T (GLU298ASP, RS1799983) GENE IN CARDIOVASCULAR ADAPTATION IN ADOLESCENT FOOTBALL PLAYERS

In recent years, among the genes associated with success in sports and adaptation to physical exertion, NOS3 (endothelial nitric oxide synthase gene) has garnered particular attention. Polymorphisms of the NOS3 gene affect nitric oxide synthesis, which in turn determines the state of endothelial function, vascular dilation, and hemo­dynamic adaptation processes. Objective. To evaluate the relationship between cardiovascular system adaptation indicators and NOS3 G894T (Glu298Asp, rs1799983) gene polymorphisms in adolescent football players. Research materials. The study included 100 adolescent football players who train regularly (AF group) and 60 adolescents who participate in sports as part of their school's physical education curriculum (SC group). Conclusion. In the study of the NOS3-G894T (rs1799983) polymorphism, the most favorable adaptation profile was observed in carriers of the GG genotype. They exhibited a lower resting heart rate, a higher incidence of physiological bradycardia, better parame­ters of autonomic heart rhythm regulation, more pronounced physiological myocardial remodeling, and optimal diastolic function values. Conversely, the presence of the T allele was associated with a decrease in the functional reserves of the cardiovascular system, a reduction in vagal nerve influence, and a shift in the autonomic balance towards sympathetic activity.