Over-expression of miR-34a Induces Rapid Cognitive Impairment and Alzheimer's Disease-like Pathology.

Over-expression of miR-34a Induces Rapid Cognitive Impairment and Alzheimer's Disease-like Pathology. Brain Res. 2019 Jul 08;:146327 Authors: Sarkar S, Engler-Chiurazzi EB, Cavendish JZ, Povroznik JM, Russell AE, Quintana DD, Mathers PH, Simpkins JW Abstract Autosomal dominant Alzheimer disease (AD) is caused by rare mutations in one of three specific genes. This is in contrast to idiopathic, late-onset AD (LOAD), which has a more polygenetic risk profile and represents more than 95% of cases. Previously, we have demonstrated that increased expression of microRNA (miRNA)-34a (miR-34a) in AD brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity. Here we report the generation of a heterozygous, conditional miR-34a overexpression mouse (miR-34aP+/-P(TetR-TetO-miR-34a) Transgenic Mice). Doxycycline-treated mice of either sex exhibited profound behavioral impairment compared to untreated groups with only 1-2 months of over-expression of miR-34a. Cognitive impairment of individual mice in T- and Y-maze tasks correlated with elevated miR-34a expression in many parts of the brain including the hippocampus and prefrontal cortex, regions which are known to be involved in this task and implicated in LOAD dysfunction. Immunocytochemistry of brain sections from mice show high amyloid β and phosphorylated tau-specific staining in the hippocampus and cortex. Analysis of protein samples from these ...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research