Applications of Arrays to Neurological Disorders

Many studies have been carried out on HD mouse models and human material to investigate the basic mechanisms of neurodegeneration of mutant HTT protein [70-72], the effects of mutant HTT protein length [73], the variability in expression changes in different regions of the brain [74], the effects of potential HD drug treatments [13, 75, 76], and to identify potential biomarkers which correlate with the progression of the disease [77]. The next sections will discuss each of these applications in turn. 

To provide an insight into the pathways involved in HD neurodegeneration, gene expression studies of the striatum were performed on the mouse model of HD, R6/2, which expresses exon 1 of the HD gene with 140 150 CAG repeats under control of the HD promoter [70], Eighty percent of cells in the mouse striatum were estimated to consist of medium spiny GABAergic neurons. Decreased neurotransmitter receptor gene expression was identified 

The dysregulation of transcription has provided a target for therapeutic intervention, and microarray analysis has been used to follow the effect of the drug in the treated samples. For example, acetylation of histones regulates 

An alternative therapeutic strategy has focused on improving cognitive features of HD, and the effect of this treatment on gene expression has been studied [76], R6/2 mice were treated from 5 weeks old, when they exhibit spatial learning difficulties, with a cocktail of tacrine (an acetylcholine esterase inhibitor, which results in a global increase of brain acetylcholine levels), moclobemide (an antidepressant that inhibits monoamine oxidase A and 

MS is an autoimmune disease that attacks the myelin sheath of oligodendrocytes around the neuronal axons. This allows the axonal cytoskeleton to be damaged, bringing about secondary axonal loss and persisting neurological dysfunction. The characteristic pathology is of a lesion or plaque in the CNS white matter, formed by inflammation and demyelination and these can be classified into active, chronic active, or chronic silent plaques [86]. 

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