Neuron stem cell NLRP6 sustains hippocampal neurogenesis to resist stress-induced depression

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

Stress Resilience among caregivers of patients with mental illness during Covid 19 pandemic

Background: COVID 19 has brought daily life to a standstill for almost all population across the world. The pandemic is a source of unexpected stress. The pandemic is causing huge pressures on all people. Resilience can help us to get through and overcome stressful hardship. Methodology: The present qualitative descriptive study conducted among caregivers of patients with mental illness at the inpatient and outpatient department of Amrita Institute of Medical Sciences, Kochi. The main objective of the study was to determine the level of stress resilience among caregivers of patients with mental illness. Secondary objectives were to find association of level of stress resilience among caregivers with various mental illness and to find the association of level of stress resilience and selected demographic characteristics. Tools used for data collection are Demographic data collection tool and Connor Davidson Stress Resilience scale. Totally 132 samples were collected using purposive sampling technique. Results: 4.54% of the respondents scores between 26 -50 points (first intermediate resilience), 53.78% of respondents scores between 51 -75 points (second intermediate resilience) and 41.66 % of respondents scores between 76- 100 points (highest resilience). None of the respondents shows lowest resilience (0-25 points). The study results reveal that most of the respondents shows second intermediate resilience towards stress. Conclusion: The study arouses a need for adopting coping strategies to improve the quality of life of caregivers. For improving the resilience, interventions like stress coping skill training or counseling services can be adopted.

Study on the fecal metabolomics of CUMS-susceptible and CUMS-resilient rats / 药学学报

Proton nuclear magnetic resonance (1H NMR) based metabolomics was applied to characterize the fecal metabolic profiles of chronic unpredictable mild stress (CUMS)-depression (CUMS-D) and CUMS-resilience (CUMS-R) rats. The fecal biomarkers and metabolic pathways involved in CUMS-D and CUMS-R were screened and identified, revealing the underlying mechanisms of two different responses of the body to the same stresses. Firstly, the classic depression model, i.e. CUMS, was constructed. According to the fecal metabolomics profiles, the model rats were divided into two groups, i.e. the CUMS-D group and the CUMS-R group. And then, the depression statuses of CUMS-D rats and CUMS-R rats were verified by their sucrose preference rates. Lastly, multivariate data analysis was applied to clarify the fecal biomarkers and corresponding metabolic pathways involving in CUMS-D and CUMS-R. The results show that compared with the control rats, the sucrose preference rates of CUMS-D rats were significantly reduced. By contrast, the sucrose preference rates of CUMS-R rats had no significant difference. At the same time, CUMS-D and CUMS-R showed both unique and shared biomarkers and pathways. Three pathways are significantly related to CUMS-D, including taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and arginine and proline metabolism. Glycerolipid metabolism and tryptophan metabolism are specific pathways related to CUMS-R. This study explores the mechanisms of the emergence of susceptible and resilience of rats under the same stimulus from a metabolomics perspective. The current findings provide not only a new perspective for studying depression, and personalized and precision treatments in clinic, but also the research and development of antidepressants.