Research Report DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington's mice (R6/2) reveals neuroinflammation and insulin associations Susan F. Crocker, Willard J. Costain, Harold A. Robertson ⁎ Brain Repair Centre, Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5 ARTICLE INFO ABSTRACT Article history: Accepted 26 February 2006 Available online 19 April 2006 Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder caused by CAG repeat expansion in the gene that codes for the protein huntingtin. The underlying neuropathological events leading to the selectivity of striatal neuronal loss are unknown. However, the huntingtin mutation interferes at several levels of normal cell function. The complexity of this disease makes microarray analysis an appealing technique to begin the identification of common pathways that may contribute to the pathology. In this study, striatal tissue was extracted for gene expression profiling from wild-type and symptomatic transgenic Huntington mice (R6/2) expressing part of the human Huntington's disease gene. We interrogated a 15 K high-density mouse EST array not previously used for HD and identified 170 significantly differentially expressed ESTs in symptomatic R6/2 mice. Of the 80 genes with known function, 9 genes had previously been identified as altered in HD. 71 known genes were associated with HD for the first time. The data obtained from this study confirm and extend previous observations using DNA microarray techniques on genetic models for HD, revealing novel changes in expression in a number of genes not previously associated with HD. Further bioinformatic analysis, using software to construct biological association maps, focused attention on proteins such as insulin and TH1-mediated cytokines, suggesting that they may be important regulators of affected genes. These results may provide insight into the regulation and interaction of genes that contribute to adaptive and pathological processes involved in HD. © 2006 Elsevier B.V. All rights reserved. Keywords: Cytokine Neuroinflammation Diabetes Neuroendocrine Neurodegeneration BRAIN RESEARCH 1088 (2006) 176 – 186 ⁎ Corresponding author. Fax: +1 902 494 6294. E-mail address: Harold.Robertson@dal.ca (H.A. Robertson). 0006-8993/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2006.02.102 available at www.sciencedirect.com www.elsevier.com/locate/brainres