Current studies are of postmortem brains.

"For Parkinson’s disease, the search for novel drug targets has involved the use of microarray technologies in combination with a technique termed ‘voxelation’, which provides a quasi-three-dimensional approach to studying changes in gene expression in animal models of Parkinson’s disease"

Target validation
full article:

http://www.sciencedirect.com/science...9ec5142ae0f0c1

Using cDNA microarray to assess Parkinson's disease models and the effects of neuroprotective drugs

Silvia Mandel, Orly Weinreb and Moussa B. H. YoudimE-mail The Corresponding Author

Abstract

The remarkable progress made by molecular biology and molecular genetics during the past decade, and the advent of the novel tools of genomics and proteomics, are expected to reveal differential expression profiles of thousands of genes and proteins involved in the degeneration of dopamine-containing cells in Parkinson's disease and allow more focused treatments according to individual genotypes. Of particular interest is the application of microarrays in drug discovery and design to identify ‘fingerprints’ as potential candidate targets for drug intervention. The major microarray findings relevant to Parkinson's disease and its neurotoxin-induced animal and cell models will be discussed, with particular reference to the neuroprotective therapeutic potential that could arise from the development of drugs ‘a la carte’.


full article:
http://www.sciencedirect.com/science...efed4daf6c9c88

Outstanding issues with microarray study of PD: strengths and weaknesses

Gene-expression microarray technology is contributing to several important developments that have emerged over the past four years, and is rapidly becoming a technique that is employed routinely in neuroscience [25 and 46]. Nonetheless, it is a measurement procedure, with a set of general limitations that must be considered when employing human, animal or cell tissue. The reproducibility among independent replicates will depend on several factors, including animals of the same genetic background, animal weight and housing conditions, and the precise dissection of the brain region affected. Well-designed studies, with regard to neurotoxin type, dose and administration regimen, and brain region targeted (specifically SNc) are needed. The most precise gene-array results will be obtained by employing isolated nigral DA-containing neurons. Methods such as single-cell PCR [47] and laser capture microdissection [48] will be of significant importance to assess differential expression in the different cell types constituting the tissue in question. If working with cell lines special attention should be given to the passage number because biochemical pathways might be impaired.

Human brain tissue deserves even more rigorous attention because of the innate problems to obtain suitable autopsy materials, with careful consideration of the disease pathology, autopsy time, age and gender of patient, drug treatment and cause of death. The diversity of cell types in the brain and the variation between different subclasses of neurons necessitates cautious follow-up. Due to the inherent complexity of nervous tissue and the need to use post-mortem material, few microarray studies on neurodegenerative diseases, including PD, have been conducted. Moreover, in contrast to cDNA microarray studies with cancer, where many biological measures of the disease reveal several orders of magnitude differences in gene expression, alterations of genes in neurological diseases appear to be much more limited and often do not exceed a twofold change [49]. Furthermore, because alterations in gene expression less than twofold are not easily detected, significant biological changes might be missed. Thus, well-designed studies need to include sufficient numbers of samples and proper statistical methods and computational analyses. Typically, confirmatory studies that employ in situ or immunohistochemistry analyses should clarify the issue. Finally, the use of clustering analysis to detect particular functional group changes in gene expression might provide a higher level of examination of gene alterations. This is particularly useful for studies that examine complex changes in gene expression over time in neurodegenerative diseases, or in cases where sample availability is limited. Because an unprecedented amount of information is produced from microarray studies, bioinformatics and modeling expertise are increasingly crucial components.




A Correlation Analysis on Multiplex Three-Dimensional Brain Gene Expression Mapping of Parkinson Disease
http://ieeexplore.ieee.org/xpls/abs_...number=4382015