Abstract

Although dystonia is the third most common movement disorder and causes muscles to contract uncontrollably, the exact mechanisms for dystonia are poorly understood. Past research on multiple forms of dystonia have implicated phospho-eIF2a pathway activity in the brain as a central source of dysfunction. This pathway is involved in responding to cellular stressors and mediating synaptic plasticity responses in the brain. The goal of this study is to identify the brain regions and developmental periods in which the pathway’s activation is disrupted in a DYT1 mouse model of childhood-onset dystonia. Western Blot analysis was used to determine the expression levels of phospho-eIF2a and total eIF2a of DYT1 and control mice at various time points in development including p0, p5, p14, p21 and p30 and in various brain regions including the striatum, cortex, cerebellum, and midbrain to determine where pathway dysregulation was most predominant. This knowledge will advance our understanding of the cellular mechanisms of dystonia and provide proof-of-principle experiments to determine whether targeting this pathway is beneficial.