Although ketamine shows a rapid and sustained antidepressant effect, the precise mechanisms underlying its effect are unknown. Recent studies indicate a key role of p11 (also known as S100A10) in depression-like behavior in rodents. The present study aimed to investigate the role of p11 in the antidepressant-like action of ketamine in chronic unpredictable mild stress (CUMS) rat model. The open-field test, forced swimming test and sucrose preference test were performed after administration of ketamine (10 mg kg−1) or a combination of ketamine and ANA-12 (a tropomyosin-related kinase B (TrkB) antagonist; 0.5 mg kg−1). The lentivirus vector for p11 was constructed to knock down the hippocampal expression of p11. In the CUMS rats, ketamine showed a rapid (0.5 h) and sustained (72 h) antidepressant effect, and its effect was significantly blocked by co-administration of ANA-12. Furthermore, ketamine significantly increased the reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of CUMS rats, whereas ketamine did not affect the expression of p11 in CUMS rats 0.5 h after administration. In addition, ketamine significantly increased the reduced ratio of p-TrkB/TrkB in the hippocampus by CUMS rats, and its effect was also blocked by ANA-12. Moreover, the reduced expression of BDNF and p11 in the hippocampus of CUMS rats was significantly recovered to control levels 72 h after ketamine administration. Interestingly, knockdown of hippocampal p11 caused increased immobility time and decreased sucrose preference, which were not improved by ketamine administration. These results suggest that p11 in the hippocampus may have a key role in the sustained antidepressant effect of ketamine in the CUMS model of depression.
Aortocaval compression is a major cause of maternal hypotension. A randomised controlled clinical trial was designed to compare two wedged supine positions for prevention of hypotension following combined spinal epidural anaesthesia for caesarean delivery. Sixty parturients undergoing elective caesarean delivery were randomly assigned to two different wedged supine positions. After the completion of subarachnoid injection, parturients were placed with either a wedge under the right pelvis (group P, pelvic wedge) or under the right lumbar region (group L, lumbar wedge). Systolic blood pressure and heart rate were recorded every minute for 20 minutes from the subarachnoid injection. Hypotension, defined as systolic blood pressure <100 mmHg or 80% of the baseline, was treated with intravenous ephedrine 5 mg. The incidence of hypotension, ephedrine use and neonatal Apgar scores and umbilical arterial pH were recorded. The incidence of hypotension was significantly higher in group P than that in group L (23/30 [77%] vs. 14/30 [47%], P=0.016). Systolic blood pressure decreased significantly in both groups at seven, eight and nine minutes (P <0.001); moreover it was lower at seven, eight and nine minutes in group P than in group L (P <0.01). Heart rate did not change significantly in either group. There were no significant differences between the two groups for Apgar score and umbilical arterial pH. A lumbar wedge is more effective than a pelvic wedge in preventing hypotension following combined spinal epidural anaesthesia for caesarean delivery, although it does not eliminate hypotension.
Proper HOXA10 expression was essential for endometrial receptivity what was crucial for successful embryo implantation in mammalian. This study confirmed that miR-182 regulated the expression levels of HOXA10 by binding to its 3' UTR, selectively downregulated HOXA10 in goat endometrial epithelium cells (gEECs) but not stromal cell (gESCs) in vitro. However, HOXA10 and miR-182 both up-expressed in the goat endometrium at gestational day 15 (D15) compared with gestational day 5 (D5), suggesting that there were some other factors regulated the expression of HOXA10 during the development of goat endometrium in vivo. What's more, HOXA10 gene silencing (HOXA10-siRNA) resulted in gEECs apoptosis in vitro, and it regulated the protein levels of oestrogen receptor a (ERa), progesterone receptor B (PRb), insulin-like growth factor 1 receptor (IGF1R), BCL-2, pleiotrophin (PTN), AKT and p-JNK in gEECs. Furthermore, HOXA10 might regulate the protein levels of endometrial receptivity biomarker genes, including vascular endothelial growth factor (VEGF), osteopontin (OPN), cyclooxygenase-2 (COX-2) and prolactin receptor (PRLR) in gEECs. In conclusion, miR-182 targeted HOXA10 selectively in EECs in vitro, and HOXA10 played an important role in maintaining the function of EECs in dairy goats.
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