Ischemic axonal injury up-regulates MARK4 in cortical neurons and primes tau phosphorylation and aggregation.

ABSTRACT: Ischemic injury to white matter tracts is increasingly recognized to play a key role in age-related cognitive decline, vascular dementia, and Alzheimer's disease. Knowledge of the effects of ischemic axonal injury on cortical neurons is limited yet critical to identifying molecular pathways that link neurodegeneration and ischemia. Using a mouse model of subcortical white matter ischemic injury coupled with retrograde neuronal tracing, we employed magnetic affinity cell sorting with fluorescence-activated cell sorting to capture layer-specific cortical neurons and performed RNA-sequencing. With this approach, we identified a role for microtubule reorganization within stroke-injured neurons acting through the regulation of tau. We find that subcortical stroke-injured Layer 5 cortical neuron

SUBMITTER: Hayden EY 

PROVIDER: S-EPMC6700776 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature