ABSTRACT
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.
ABSTRACT
ObjectiveTo study the the efficacy and safety of joint rabeprazole mosapride treatment of reflux esophagitis(RE). Methods110 patients Confirmed by endoscopy reflux esophagitis were randomly divided into treatment group and control group 55 cases. Treatment group:oral rabeprazole 10mg, sooner or later, a second fasting taking each mosapride 5mg,3 times/day, fasting and a half hours to take; control group: omeprazole 20mg/day, taken before meals ,mosapride taking followed. 2 groups of patients were completed 6 weeks of treatment ,the clinical efficacy and safety were observed. ResultsThe clinical total effective rate of symptom relief( symptom improvement and endoscopic remission and mucosal lesions ) were 94.5％ for the treatment group ( 52/55 ), control group 76.4％ ( 42/55), the efficiency of the treatment group was superior in the control group ( P ＜ 0.05 ). ConclusionRabeprazole joint mosapride treatment of reflux esophagitis could improve symptoms rapidly,and clinical efficacy was superior to omeprazole mosapride treatment of reflux esophagitis, and was safe and reliable.