Ischemic stroke is a serious threat to human life and health, which is often accompanied by cerebral ischemia-reperfusion (I/R) injury in clinic. Ischemic postconditioning (IPostC) is a short period of mild non-fatal ischemia in the early stage of cerebral I/R injury. However, there are few reports about the protective effect of IPostC. In the present study, we investigated the neuroprotective effect of IPostC in a mice model of ischemia induced by the middle cerebral artery occlusion (MCAO). MicroRNA-124(miR-124) is a small RNA highly expressed in the brain. Several studies have shown that miR-124 is significantly decreased in IPostC. Therefore, we hypothesize that IPostC may play an important role by downregulating the expression of miR-124. Mice were treated with cerebral I/R and IPostC treatment on the basis of MCAO. The results showed that IPostC significantly reduced neurobehavioral deficits and decreased brain infarct volume. Moreover, we also found that inhibiting miR-124 effectively reduced neurons/cells apoptosis in vivo and vitro. In addition, western blot analysis of apoptosis-related proteins and PI3K/Akt2 signaling pathway proteins showed that downregulation of miR-124 significantly decreased the expression of Caspase-3 and BAX, and increased the expression of anti-apoptotic protein Bcl-2. Inhibition of miR-124 also increase PI3K/Akt/mTOR signaling pathway, thus inhibiting cell apoptosis and autophagy. However, overexpression of miR-124 weakens the protective effect of IPostC. These observations suggest that IPostC exerts its neuroprotective effect through negatively regulating PI3K/Akt2 signaling pathway by miR-124.
Objective(s): Previous studies have reached different conclusions regarding an association between apolipoprotein E (APOE) polymorphisms and depression. This meta-analysis was designed to clarify these controversies. Materials and Methods: Literatures were identified reviewing the national and international databases. The eligible articles for meta-analysis were determined by quality assessment and implementation of inclusion/exclusion criteria. This meta-analysis was performed using Review Manager 5.2 software. The odds ratios (ORs) with corresponding 95% confidence interval (CIs) were calculated using a fixed effects model. Funnel plots and Egger's regression tests were used to assess the publication bias. Results: A total of nine studies that met the inclusion criteria were identified by performing a comprehensive search on the association between APOE polymorphisms and depression. APOE epsilon 4 allele was significantly associated with depression (allele: OR=1.36, 95% CI=1.11-1.66, P=0.003; dominant: OR=1.34, 95% CI=1.06-1.68, P=0.001; recessive: OR=1.11, 95% CI=0.45-2.76, P=0.82). HAMD scores were higher in depression patients with-APOE epsilon 4 genotype than who without-APOE epsilon 4 genotype (OR=0.96, 95% CI=0.16-1.76, P=0.02). Conclusion: APOE epsilon 4 allele increased the depression risk; depressive patients carrying APOE epsilon 4 allele had more severe depressive symptoms.
Background: The dementia and affective disorders are common non-motor features in patients with essential tremor (ET). However, the relationship of ET with cognitive impairments and affective disorders remains controversial. This meta-analysis aimed to analyze the association of ET with dementia and affective disorders.Methods: Original studies published from January 1999 to October 2019 were systematically searched from the database of Medline (OvidSP), EMBASE (OvidSP), and the Cochrane Central Register of Controlled Trials. Pooled standard mean difference (SMD, random effect model), odds ratios (ORs), relative risk (RR), and 95% CI were calculated.Results: Compared with the Non-ET group, patients with ET had significantly lower Mini-Mental State Examination (MMSE) score (SMD, −1.16; 95% CI, −1.75 to −0.58; p = 0.0001) and had significantly higher depressive and anxiety symptoms scale score (SMD, 0.55; 95% CI, 0.22–0.87; p = 0.0009). The OR for dementia and affective disorders in individuals with ET compared with individuals without ET was 2.49 (95% CI, 2.17–2.85, p < 0.00001). While there was no significant difference in Montreal Cognitive Assessment (MoCA) score between ET and Non-ET groups (SMD, −0.52; 95% CI, −0.16 to 0.13; p = 0.23), there was a significant difference in the risk of mortality between ET and Non-ET groups (RR = 4.69, 95% CI, 2.18–10.07).Conclusion: The non-motor symptoms should not be neglected among patients with ET. However, the causal relationship between ET and dementia, depression, and anxiety is unclear.