ABSTRACT
Epileptogenesis in the temporal lobe elicits regulation of gene expression and protein translation, leading to reorganization of neuronal networks. In this process, miRNAs were described as being regulated in a cell-specific manner, although mechanistics of miRNAs activity are poorly understood. The specificity of miRNAs on their target genes depends on their intracellular concentration, reflecting the balance of biosynthesis and degradation. Herein, we confirmed that pilocarpine application promptly (<30 min) induces status epilepticus (SE) as revealed by changes in rat electrocorticogram particularly in fast-beta range (21-30 Hz). SE simultaneously upregulated XRN2 and downregulated PAPD4 gene expression in the hippocampus, two genes related to miRNA degradation and stability, respectively. Moreover, SE decreased the number of XRN2-positive cells in the hilus, while reduced the number of PAPD4-positive cells in CA1. XRN2 and PAPD4 levels did not change in calretinin- and CamKII-positive cells, although it was possible to determine that PAPD4, but not XRN2, was upregulated in parvalbumin-positive cells, revealing that SE induction unbalances the accumulation of these functional-opposed proteins in inhibitory interneurons that directly innervate distinct domains of pyramidal cells. Therefore, we were able to disclose a possible mechanism underlying the differential regulation of miRNAs in specific neurons during epileptogenesis.
Subject(s)
Hippocampus/pathology , MicroRNAs/genetics , Neurons/metabolism , RNA Stability/genetics , Seizures/chemically induced , Seizures/genetics , Animals , Exoribonucleases/genetics , Exoribonucleases/metabolism , GABAergic Neurons/metabolism , Gene Expression Regulation , Interneurons/metabolism , Male , MicroRNAs/metabolism , Organ Specificity/genetics , Parvalbumins/metabolism , Pilocarpine , Rats, Wistar , Seizures/pathology , Status Epilepticus/chemically induced , Status Epilepticus/genetics , Status Epilepticus/pathology , Subcellular Fractions/metabolism , mRNA Cleavage and Polyadenylation Factors/genetics , mRNA Cleavage and Polyadenylation Factors/metabolismABSTRACT
OBJECTIVES: We aimed to investigate the association of depression with cardiovascular risk factors and diseases (CVRFD) in a large population-based sample. METHODS: This cross-sectional study included 1012 deceased individuals greater than 50 years of age from a general autopsy service located in São Paulo, Brazil. Demographics, socioeconomic profile, and CVRFD information were collected by caregivers from the deceased individuals from the Brain Bank of the Brazilian Aging Brain Study Group. Depression diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Mental Disorders was the main outcome. RESULTS: Depression was associated with female gender (odds ratio (OR) = 1.86; 95% confidence interval (CI) = 1.28-2.71, p = 0.001), widowhood (OR = 1.54; 95% CI = 1.03-2.32, p = 0.04), physical inactivity (OR = 1.61; 95% CI = 1.15-2.26, p = 0.006), and smoking (OR = 2.03; 95% CI = 1.40-2.95, p < 0.001) after multivariate logistic regression analysis. Other CVRFD were not associated with the presence of depression. CONCLUSIONS: In our cross-sectional study, sedentary individuals and smokers showed a higher chance of depression during lifetime. Measures to control these common risk factors could decrease the incidence of depression.
