BackgroundMany clinical studies have shown a correlation between plasma cortisol and neurological disorders. This study explored the causal relationship between plasma cortisol and dementia, epilepsy and multiple sclerosis based on Mendelian randomization (MR) method.MethodsData were taken from the summary statistics of a genome-wide association study, FinnGen consortium and United Kingdom Biobank. Dementia, epilepsy, and multiple sclerosis were used as outcomes, and genetic variants associated with plasma cortisol were used as instrumental variables. The main analysis was performed using the inverse variance weighted method, and the results were assessed according to the odds ratio (OR) and 95% confidence interval. Heterogeneity tests, pleiotropy tests, and leave-one-out method were conducted to evaluate the stability and accuracy of the results.ResultsIn two-sample MR analysis, the inverse variance weighted method showed that plasma cortisol was associated with Alzheimer’s disease (AD) [odds ratio (95% confidence interval) = 0.99 (0.98-1.00), P = 0.025], vascular dementia (VaD) [odds ratio (95% confidence interval) = 2.02 (1.00-4.05), P = 0.049)], Parkinson’s disease with dementia (PDD) [odds ratio (95% confidence interval) = 0.24 (0.07-0.82), P = 0.023] and epilepsy [odds ratio (95% confidence interval) = 2.00 (1.03-3.91), P = 0.042]. There were no statistically significant associations between plasma cortisol and dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and multiple sclerosis.ConclusionThis study demonstrates that plasma cortisol increase the incidence rates of epilepsy and VaD and decrease the incidence rates of AD and PDD. Monitoring plasma cortisol concentrations in clinical practice can help prevent diseases, such as AD, PDD, VaD and epilepsy.

BackgroundDementia is a clinical syndrome commonly seen in the elderly individuals. With the prevalence of dementia, the incidence of neuropsychiatric symptoms in dementia patients is increasing annually. Agitation, as one of the neuropsychiatric symptoms, has a serious impact on the quality of life of patients with dementia. Several antidepressant drugs have been shown to be effective for treating agitated behavior symptoms in patients with dementia, but there are no direct comparisons among those drugs. Therefore, we carried out a network meta-analysis (NMA) to examine the efficacy and safety of those antidepressant drugs.MethodsWe searched eight databases (PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, China National Knowledge Infrastructure, VIP Database and China biomedical literature service) from their inception to 6 November 2022. Randomized controlled trials (RCTs) reporting the efficacy and safety of antidepressant drugs in treating agitated behavior symptoms in patients with dementia were included in our analysis. The quality assessment was carried out by two researchers individually and the analysis was based on the frequency method.ResultsTwelve articles with 1,146 participants were included in our analysis. Based on the outcome of the agitation score, treatment with citalopram (standardized mean difference, SMD = −0.44, 95% confidence interval, 95% CI = −0.72 to −0.16) showed significant benefits over the placebo group. Treatment with trazodone (odds ratio, OR = 4.58, 95% CI = 1.12–18.69) was associated with a higher risk of total adverse events compared with a placebo treatment.ConclusionAmong the antidepressant drugs included in this study, treatment with citalopram was probably the only optimal intervention, when considering the improvement from baseline to the end of the intervention, and there was not a statistically significant difference in safety when compared with a placebo treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier: PROSPERO, CRD42022320932.

IntroductionBrain tissue is extremely sensitive to hypoxia/reoxygenation (H/R) injury, which can easily cause irreversible damage to neurons. H/R injury can induce neuronal apoptosis through glutamate-mediated excitotoxicity. N-methyl-d-aspartate receptor (NMDAR) is one of the main receptors of excitatory glutamate, and blocking NMDAR protects brain tissue from ischemic and hypoxic injury. However, NMDAR hypofunction can also cause psychotic symptoms or cognitive impairment. There is still a lack of systematic research on the changes in the proteome and transcriptome in neuronal cells under conditions of NMDAR hypofunction and H/R injury.MethodsWe compared the changes in the proteome, transcriptome and lncRNA expression levels in neurons after NMDAR knockdown and H/R by isobaric tags for relative and absolute quantitation (iTRAQ) and RNA sequencing (RNA-Seq).ResultsThe results showed that the proteins Rps9, Rpl18 and Rpl15 and the lncRNAs XLOC_161072 and XLOC_065271 were significantly downregulated after NMDAR knockdown but upregulated after H/R; in contrast, the mRNAs Bank1 and Pcp4l1 and the lncRNAs XLOC_159404 and XLOC_031922 were significantly upregulated after NMDAR knockdown but downregulated after H/R.DiscussionIn this study, we demonstrated the characterization of protein, mRNA, and lncRNA expression profiles in neurons following NMDAR knockdown and H/R injury. These molecules are involved in multiple biological functions and signaling pathways, and their roles in neurons lacking NMDAR and subjected to H/R injury deserve further study. Additionally, we found that lncRNAs respond fastest to hypoxic stimulation and that Gapdh is not suitable as a reference protein for NMDAR-reduced neuron-related experiments.