The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus.

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.SIGNIFICANCE STATEMENT Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. Here, we examined the behaviors of loss- and gain-of-function of Slack channel mice in elevated plus maze and open field tests and found the anxiolytic role of the Slack channel. By altering the Slack channel expression in the specific neuronal circuit, we demonstrated that the Slack channel played its anxiolytic role by decreasing the excitability of BLA-vHPC glutamatergic projections. Our data reveal the role of the Slack channel in the regulation of anxiety, which may provide a potential molecular target for anxiolytic therapies.

Positive association between triglyceride glucose index and central systolic blood pressure among hypertensive adults.

BACKGROUND: While studies have suggested the association between triglyceride-glucose (TyG) index, a reliable surrogate for insulin resistance and hypertension data are limited to the correlation of TyG and central blood pressure. This study aims to test the hypothesis that a higher TyG index is associated with elevated central systolic blood pressure (cSBP). METHODS: A total of 9249 Chinese hypertensive adults from the H-type Hypertension and Stroke Prevention and Control Project were analyzed in this study. cSBP was measured noninvasively using an A-Pulse CASPro device. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Smoothing curve and multivariate linear regression models [beta coefficient (ß) with 95% CI] were applied to analyze the association between TyG index and cSBP. Subgroup analyses were conducted to explore potential modifications to such a correlation. RESULTS: The overall mean TyG index is 8.8 ± 0.7, and the total mean cSBP is 131.3 ± 12.8 mmHg. TyG index was observed to be independently and positively associated with cSBP among the total population (ß = 0.92, 95% CI: 0.53-1.31, P < 0.001), and participants who do not use antihypertensive drugs (ß = 1.03, 95% CI: 0.46-1.60, P < 0.001), which is in accordance with the result of the smoothing curve. The association between TyG index and cSBP appears robust in all tested subgroups. CONCLUSIONS: TyG index is positively and independently associated with cSBP among hypertensive adults. Our study result suggests that TyG index might serve as an effective marker for vascular function.

Individual and joint effects of borderline ankle-brachial index and high plasma total homocysteine on all-cause death in hypertensive adults.

BACKGROUND: The cardiovascular hazards of total homocysteine (tHcy) are long known. In addition, despite the acknowledgment on the importance of low ankle-brachial index (ABI) (< 0.9), borderline ABI (0.91-0.99) was once commonly overlooked. This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population. METHODS: This study included 10,538 participants from China H-type Hypertension Registry Study. ABI was described into two groups: normal ABI (1.00-1.40) and borderline ABI. tHcy level was also divided into two groups: < 15.02 and ≥ 15.02 µmo/L. Four groups were analyzed, using COX proportional hazard regression model, separately and pairwise to observe the independent and joint effect on all-cause death. RESULTS: A total of 126 (1.2%) deaths were observed in the 1.7 years follow-up time. Borderline ABI has a higher predicted risk of death than normal ABI (HR = 1.87, 95%CI: 1.17-3.00) after adjusting for potential covariates. Compare with tHcy level < 15.02 µmo/L (low tHcy), those with tHcy ≥ 15.02 µmo/L (high tHcy) had higher risk to event outcome (HR = 1.99, 95% CI: 1.30-3.05). According to the cumulative hazard curve, group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups. Among those with borderline ABI, participants with high tHcy had higher death risk than those with low tHcy, nevertheless, no significant different between borderline and normal ABI among those with low tHcy levels. CONCLUSIONS: Borderline ABI and tHcy level both have independent predictive value on all-cause death. The combined group of borderline ABI and high tHcy has highest risk factor of outcomes, which suggested the mutual additive value of borderline ABI and tHcy. More attention should be given to the importance of borderline ABI in hypertensive population, especially with elevated tHcy level.

The Correlation Between Olfactory Test and Hippocampal Volume in Alzheimer's Disease and Mild Cognitive Impairment Patients: A Meta-Analysis.

Background: Previous studies have reported that olfactory identification deficits may be the earliest clinical features of Alzheimer's disease (AD). However, the association between odor identification and hippocampal atrophy remains unclear. Objective: This meta-analysis quantified the correlation between odor identification test scores and hippocampal volume in AD. Method: A search of the PUBMED, EMBASE, and WEB OF SCIENCE databases was conducted from January 2003 to June 2020 on studies with reported correlation coefficients between olfactory identification score and hippocampal volume in patients with amnestic AD or mild cognitive impairment (MCI). The quality of the studies was assessed using the Newcastle-Ottawa quality assessment scale (NOS). Pooled r-values were combined and computed in R studio. Results: Seven of 627 original studies on AD/MCI using an olfactory identification test (n = 902) were included. A positive correlation was found between hippocampal volume and olfactory test scores (r = 0.3392, 95% CI: 0.2335-0.4370). Moderator analysis showed that AD and MCI patients were more profoundly correlated than normal controls (AD: r = 0.3959, 95% CI: 0.2605-0.5160; MCI: r = 0.3691, 95% CI: 0.1841-0.5288; NC: r = 0.1305, 95% CI: -0.0447-0.2980). Age difference and patient type were the main sources of heterogeneity in this analysis. Conclusion: The correlation appears to be more predominant in the cognitive disorder group (including MCI and AD) than in the non-cognitive disorder group. Age is an independent factor that affects the severity of the correlation during disease progression. The mildness of the correlation suggests that olfactory tests may be more accurate when combined with other non-invasive examinations for early detection. Systematic Review Registration: https://inplasy.com/, identifier INPLASY202140088.