TSHR signaling promotes hippocampal dependent memory formation through modulating Wnt5a/ß-catenin mediated neurogenesis.

Subclinical hyperthyroidism is defined biochemically as a low or undetectable thyroid-stimulating hormone (TSH) with normal thyroid hormone levels. Low TSHR signaling is considered to associate with cognitive impairment. However, the underlying molecular mechanism by which TSHR signaling modulates memory is poorly understood. In this study, we found that Tshr-deficient in the hippocampal neurons impairs the learning and memory abilities of mice, accompanying by a decline in the number of newborn neurons. Notably, Tshr ablation in the hippocampus decreases the expression of Wnt5a, thereby inactivating the ß-catenin signaling pathway to reduce the neurogenesis. Conversely, activating of the Wnt/ß-catenin pathway by the agonist SKL2001 results in an increase in hippocampal neurogenesis, resulting in the amelioration in the deficits of memory caused by Tshr deletion. Understanding how TSHR signaling in the hippocampus regulates memory provides insights into subclinical hyperthyroidism affecting cognitive function and will suggest ways to rationally design interventions for neurocognitive disorders.

Association Between Monocyte-to-High-Density Lipoprotein Ratio and Prediabetes: A Cross-Sectional Study in Chinese Population.

Background: The monocyte-to-high-density lipoprotein cholesterol (MHR) ratio has been linked to metabolic disorders. However, there is limited research on the predisposition to MHR and prediabetes. Hence, we conducted a study to investigate the relationship between MHR and the prevalence of prediabetes. Methods: In total, 85,293 participants were included in our cross-sectional observational study. Multivariable regression analysis, subgroup analyses, and interaction testing were used to determine the relationship between MHR and prediabetes. To explore the non-linear association of MHR with prediabetes risk, generalized additive model (GAM) and smoothing splines were applied. The threshold effect analysis of MHR on the risk of prediabetes was further employed to identify the turning point. Results: After controlling for covariates, the results indicated that a positive correlation persisted between MHR and prediabetes (odds ratio (OR) =1.64, 95% confidence interval (CI), 1.48-1.82), and subgroup analyses found a more robust correlation between MHR and prediabetes in individuals with lower age, SBP, DBP, TG, TC and higher values of BMI and LDL-C than in their counterparts. Additionally, the correlation between MHR and the risk of prediabetes was found to be non-linear, with a turning point of -0.4 (Log-Likelihood Ratio, P< 0.001). The impact of variables on the two sides of the turning point were 1.94 (1.72, 2.19) and 0.88 (0.69, 1.14). Conclusion: The positive correlation between MHR and the risk of prediabetes in Chinese participants was observed to be non-linear, and MHR ≤ -0.4 was strongly positively correlated with prediabetes risk.