Up-regulation of cell division cycle 20 expression alters the morphology of neuronal dendritic spines in the nucleus accumbens by promoting FMRP ubiquitination.

The nucleus accumbens (NAc) is the key area of the reward circuit, but its heterogeneity has been poorly studied. Using single-cell RNA sequencing, we revealed a subcluster of GABAergic neurons characterized by cell division cycle 20 (Cdc20) mRNA expression in the NAc of adult rats. We studied the coexpression of Cdc20 and Gad1 mRNA in the NAc neurons of adult rats and assessed Cdc20 protein expression in the NAc during rat development. Moreover, we microinjected AAV2/9-hSyn-Cdc20 with or without the dual-AAV system into the bilateral NAc for sparse labeling to observe changes in the synaptic morphology of mature neurons and assessed rat behaviors in open field and elevated plus maze tests. Furthermore, we performed the experiments with a Cdc20 inhibitor, Cdc20 over-expression AAV vector, and Cdc20 conditional knockout primary striatal neurons to understand the ubiquitination-dependent degradation of fragile X mental retardation protein (FMRP) in vitro and in vivo. We confirmed the mRNA expression of Cdc20 in the NAc GABAergic neurons of adult rats, and its protein level was decreased significantly 3 weeks post-birth. Up-regulated Cdc20 expression in the bilateral NAc decreased the dendritic spine density in mature neurons and induced anxiety-like behavior in rats. Cdc20-APC triggered FMRP degradation through K48-linked polyubiquitination in Neuro-2a cells and primary striatal neurons and down-regulated FMRP expression in the NAc of adult rats. These data revealed that up-regulation of Cdc20 in the bilateral NAc reduced dendritic spine density and led to anxiety-like behaviors, possibly by enhancing FMRP degradation via K48-linked polyubiquitination.

Quercetin Protects Against Global Cerebral ischemia‒reperfusion Injury by Inhibiting Microglial Activation and Polarization.

Background: This study aims to investigate the protective effect of quercetin against global cerebral ischemia‒reperfusion (GCI/R) injury in rats and elucidate the underlying mechanism. Methods: A GCI/R injury rat model was established using a four-vessel occlusion (4-VO) method. An oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was induced in BV2 cells. The extent of injury was assessed by evaluating neurological deficit scores (NDS) and brain water content and conducting behavioral tests. Pathomorphological changes in the prefrontal cortex were examined. Additionally, the study measured the levels of inflammatory cytokines, the degree of microglial activation and polarization, and the protein expression of Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor inducing interferon-ß (TRIF). Results: Quercetin pretreatment significantly ameliorated neurological impairment, improved learning and memory abilities, and reduced anxiety in rats subjected to GCI/R injury. Furthermore, quercetin administration effectively mitigated neuronal injury and brain edema. Notably, it suppressed microglial activation and hindered polarization toward the M1 phenotype. Simultaneously, quercetin downregulated the expression of TLR4 and TRIF proteins and attenuated the release of IL-1ß and TNF-α. Conclusion: This study highlights the novel therapeutic potential of quercetin in alleviating GCI/R injury. Quercetin demonstrates its neuroprotective effects by inhibiting neuroinflammation and microglial activation while impeding their transformation into the M1 phenotype through modulation of the TLR4/TRIF pathway.

Risk factors for emergence agitation during the awakening period in elderly patients after total joint arthroplasty: a retrospective cohort study.

OBJECTIVES: This study aimed to explore the incidence and risk factors for emergence agitation (EA) in elderly patients who underwent total joint arthroplasty (TJA) under general anaesthesia, and to assess their predictive values. DESIGN: Single-centre retrospective cohort study. SETTING: A 1600-bed general tertiary hospital in China. PARTICIPANTS: This study enrolled 421 elderly patients scheduled for elective primary TJA under general anaesthesia. PRIMARY AND SECONDARY OUTCOME MEASURES: EA was assessed using the Richmond Agitation Sedation Scale during the awakening period after surgery in the post-anaesthesia care unit. Risk factors for EA were identified using univariate and multivariable logistic analyses. The receiver operating characteristic (ROC) curve was used to assess the predictive values of the risk factors for EA. RESULTS: The incidence of EA in elderly patients who underwent TJA was 37.6%. According to the multivariable logistic analysis, postoperative pain (95% CI: 1.951 to 3.196), male sex (95% CI: 1.781 to 6.435), catheter-related bladder discomfort (CRBD) (95% CI: 4.001 to 15.392) and longer fasting times for solids (95% CI: 1.260 to 2.301) and fluids (95% CI: 1.263 to 2.365) were independent risk factors for EA. As shown by the ROC analysis, postoperative pain and fasting times for solids and fluids had good predictive values, with areas under the ROC curve equalling 0.769, 0.753 and 0.768, respectively. CONCLUSIONS: EA is a common complication after TJA in elderly patients. Some risk factors, including postoperative pain, male sex, CRBD and longer fasting times, can increase the incidence of EA. These risk factors may contribute to identifying high-risk patients, which facilitates the development of effective strategies to prevent and treat EA. TRIAL REGISTRATION NUMBER: ChiCTR1800020193.