The role of BDNF in Huntington’s Disease: A Targeted Analysis of 12 Microarray Studies

Abstract

Objectives

Huntington’s disease (HD) is a common hereditary neurodegenerative disorder. Pathogenesis is strongly associated with mutation of the protein huntingtin (HTT). This study focuses on the REST/BDNF pathway and provides statistical analysis on expression levels of many genes involved in this pathway in HD and normal subjects.

Methods

12 recent microarray studies were systematically selected from the Gene Expression Omnibus (GEO). Over-representation analysis was performed on all assayed genes using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Detailed analysis of genes involved in BDNF expression, delivery, and response was performed and Fischer’s combined probability test was applied to combine findings across the 12 selected studies.

Results

Our findings suggest down-regulation of BDNF expression in HD-affected compared to controls. Analysis of the gene expressions of REST and AKT2 suggests that BDNF expression may be correlated negatively with REST expression and positively with AKT2 expression.

Conclusions

The changes in BDNF expression in HD suggest that impairment of the expression, delivery, and downstream effects of BDNF may play a role in HD pathogenesis.