Stress induces region specific alterations in microRNAs expression in mice

Several studies have demonstrated that exposure to both acute and chronic aversive stimuli can affect neural activity in different brain areas. In particular it has been shown that stressful events can induce not only short-term changes in neural transmission and gene regulation, but also long-term changes that can lead to structural modification. In this study we investigated, in CD1 mice, the effects of single or repeated exposures to restraint stress (2 h for I or 5 consecutive days) in the frontal cortex on a crucial class of gene expression regulators, the microRNAs (miRs).First we performed a microarray profiling on RNA extracted from the frontal cortex of mice exposed to acute or repeated restraint stress. The results indicated a Prominent increase in the expression levels of different miRs after acute stress while only minor changes were observed after repeated restraint. The Northern blot analysis on selected miRs confirmed an increase after acute restraint for let-7a, miR-9 and miR26-a/b. Finally, Northern blot analysis of the selected miRs on RNA extracted from the hippocampus of stressed mice demonstrated that such changes were region specific, as no differences were observed in the hippocampus. These data suggest that control of mRNA translation through miRs is an additional mechanism by which stressful events regulates protein expression in the frontal cortex. (C) 2009 Elsevier B.V. All rights reserved

Phosphorylation of S845 GluA1 AMPA receptors modulates spatial memory and structural plasticity in the ventral striatum.

The function of AMPA receptors phosphorylation in synaptic plasticity has been dissected in many in vitro models but its role and dynamics on experience-dependent plasticity are still unclear. Here we studied the effects of AMPA receptor manipulations in the ventral striatum, where glutamatergic transmission is known to mediate spatial memory. We first demonstrate that intra-ventral striatal administrations of the AMPA receptors blocker, NBQX, dose dependently impair performance in the Morris water maze. We also report that spatial learning induced a time-limited increase in GluA1 phosphorylation in this same brain region. Finally, through focal, time-controlled ventral striatal administrations of an RNA aptamer interfering with GluA1-S845 phosphorylation, we demonstrate that phosphorylation at this site is a necessary requirement for spatial memory formation and for the synaptic remodeling underlying it. These results suggest that modulation of AMPA receptors by S845 phosphorylation could act as an essential starting signal leading to long-term stabilization of spatial memories

microRNAs Modulate Spatial Memory in the Hippocampus and in the Ventral Striatum in a Region-Specific Manner

MicroRNAs are endogenous, noncoding RNAs crucial for the post-transcriptional regulation of gene expression. Their role in spatial memory formation, however, is poorly explored. In this study, we analyzed learning-induced microRNA expression in the hippocampus and in the ventral striatum. Among miRNAs specifically downregulated by spatial training, we focused on the hippocampus-specific miR-324-5p and the ventral striatum-specific miR-24. In vivo overexpression of the two miRNAs demonstrated that miR-324-5p is able to impair memory if administered in the hippocampus but not in the ventral striatum, while the opposite is true for miR-24. Overall, these findings demonstrate a causal relationship between miRNA expression changes and spatial memory formation. Furthermore, they provide support for a regional dissociation in the post-transcriptional processes underlying spatial memory in the two brain structures analyzed

Quality improvement intervention to increase colorectal cancer screening at the primary care setting: a cluster-randomised controlled trial

Background Approximately 81% of deaths in Argentina are from chronic non-communicable diseases and 21% caused by cancer. Colorectal cancer (CRC) is the second most frequent cancer in Argentina. Even though CRC screening has been recommended for adults from 50 to 75 years old by using a faecal immunochemical test (FIT) annually, screening rates remain below 20% in the country.Methods We conducted an 18-month, two-arm, pragmatic cluster-randomised controlled trial evaluating the effect of a quality improvement intervention, based on the Plan-Do-Study-Act cycles, considering barriers and catalysts to articulate theory and practice, to increase CRC screening rates using FITs at primary care level. The study involved ten public primary health centres in Mendoza province, Argentina. The primary outcome measure was the rate of effective CRC screening. Secondary outcomes were the rate of participants with a positive FIT, tests with invalid results and the rate of participants referred for colonoscopy.Results Screening was effective in 75% of the participants in the intervention arm vs 54.2% in the control arm, OR 2.5 (95% CI 1.4 to 4.4, p=0.001). These results remained unchanged after adjusting for individual demographic and socioeconomic characteristics. Regarding secondary outcomes, the overall prevalence of positive tests was 17.7% (21.1% in the control arm and 14.7% in the intervention arm, p=0.3648). The overall proportion of participants with inadequate test results was 5.2% (4.9% in the control arm vs 5.5% in the intervention arm, p=0.8516). All the participants with positive tests were referred for colonoscopy in both groups.Conclusions An intervention based on quality improvement strategies proved to be highly successful in increasing effective CRC screening in Argentina’s primary care setting within the public healthcare system.Trial registration number NCT04293315