Mouse anti-Human BACE1 monoclonal antibody, clone 3D2

Mild repetitive traumatic brain injury (rTBI) induces chronic behavioral and cognitive alterations and increases the risk for dementia. Currently, there are no therapeutic strategies to prevent or mitigate chronic deficits associated with rTBI. Previously we developed an animal model of rTBI that recapitulates the cognitive and behavioral deficits observed in humans. We now report that rTBI results in an increase in risk-taking behavior in male but not female mice. This behavioral phenotype is associated with chronic activation of the integrated stress response and cell-specific synaptic alterations in the type A subtype of layer V pyramidal neurons in the medial prefrontal cortex. Strikingly, by briefly treating animals weeks after injury with ISRIB, a selective inhibitor of the integrated stress response (ISR), we (1) relieve ISR activation, (2) reverse the increased risk-taking behavioral phenotype and maintain this reversal, and (3) restore cell-specific synaptic function in the affected mice. Our results indicate that targeting the ISR even at late time points after injury can permanently reverse behavioral changes. As such, pharmacological inhibition of the ISR emerges as a promising avenue to combat rTBI-induced behavioral dysfunction.

MicroRNAs (miRNAs) are considered among the most reliable biomarkers to diagnose and predict Alzheimer's disease (AD), due to their regulatory nature. The main goal of this study was to evaluate the expression of miR4422 and miR3714, as the main regulators of GSAP and BACE1 expression, in AD patients compared with healthy subjects. Twenty patients with a mild to moderate AD (58-71 years old) and 15 healthy subjects (58-73 years old) participated in this study. The expression levels of miR4422 and miR3714 as the target genes and 5S rRNA and miRlet7a-5p as the reference genes were measured in the two groups. To compare the expression between the case and the control groups, the t test or the Wilcoxon test was used, based on the data distribution patterns. The efficiencies of amplification of the miR4422, miR3714, 5S rRNA, and miRlet7a-5p genes all were in the acceptable range. The mean miR4422-5S rRNA dCt value was significantly different between the two groups (p = 0.018). The relative fold change of the expression was 0.43. The mean miR4422-miRlet7a-5p dCt value (p = 0.41), the mean miR3714-5S rRNA dCt value (p = 0.10), and the mean miR3714-miRlet7a-5p dCt value (p = 0.063) were not significantly different between the two groups. We indicated that miR4422 could be a reliable biomarker for Alzheimer's diagnosis. It seems that the reduced expression of miR4422 that targets GSAP and BACE1 expression can lead to an increase in the formation of A beta plaque.