REST is Present in Human Control and Huntington's Disease Neurons.

Abstract

AIMS: The repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master regulator of neuronal gene expression. REST/NRSF functions by recruiting other co-factors to genomic loci that contain the repressor element 1/neuron restrictive silencer element (RE1/NRSE) binding motif. In brain, demonstration of REST protein presence in neurons has remained controversial. However, RE1/NRSE containing neuronal genes are actively modulated and REST dysregulation is implicated in Huntington's Disease (HD). We aimed to investigate REST distribution in autopsy brain from control and HD patients. METHODS: Brain tissues from 6 controls and 6 HD cases (Vonsattel grade 3 and 4) were investigated using immunohistochemical analysis. RESULTS: REST was present in neurons and glial cells of the cortex, caudate nucleus, hippocampus and cerebellum. REST labeling was mainly cytoplasmic in neurons while preferential nuclear staining of REST was found in glial cells. We also found that REST and huntingtin (HTT) colocalize in human neurons. Low levels of cytoplasmic REST were detected in neurons of the HD cortex and caudate but no direct relationship between decreased neuronal REST expression and disease grade was observed. CONCLUSIONS: These data support the notion of REST presence in human brain neurons and glial cells and indicate the importance of developing compounds able to restore REST-regulated transcription of neuronal genes in HD.