Gene, Express Thyself: The Use of DNA Microarrays in Epilepsy Research

What is gene expression? How is it relevant to epilepsy?
Genes are the segments of our DNA, or "genetic code," that are used to make proteins, one of the principal components of cells. "Gene expression" is the flow of genetic information from a gene to a protein. It is one of the fundamental biological processes that enable our cells to grow, survive, and function. The ability of this process to proceed properly is therefore critical to our own development, longevity, and health in general. Inappropriate gene expression, which may happen in response to an injury or as the result of a genetic mutation, is responsible for countless diseases, including many types of epilepsy.

What are DNA microarrays?
DNA microarrays, often referred to as "gene chips," are tools used in the laboratory to measure levels of gene expression in a particular cell or tissue. Microarrays are constructed by positioning a piece of DNA on a membrane or glass matrix. This DNA segment corresponds to a particular gene and serves as a probe to detect the level of expression of that gene in the test sample. A second DNA probe, corresponding to a different gene, is then positioned next to that, and so on, to form the microarray, which can ultimately represent hundreds or thousands of genes. Biological samples are then applied to the microarray to determine the level of expression of each of the arrayed genes within the sample. In a typical sample, some genes will be highly expressed, some will be expressed at intermediate levels, and some will have no expression at all. The overall profile of gene expression can then be examined for changes between different conditions (for example, the presence or absence of a disease), or for changes over time in the same condition or the same subject (before treatment versus after treatment, for instance). This technique enables the researcher to analyze the responses of thousands of genes simultaneously, an extremely powerful tool in characterizing the cell or tissue of interest.

After the test sample is applied to the DNA microarray, the microarray at high magnification resembles a grid of dots of varying intensities, ranging from black to gray to white. Each dot represents an individual gene, and the intensity of that dot is proportional to that gene's level of expression in the test sample. Black dots indicate little or no gene expression and white dots indicate high levels of expression. Sophisticated computer analysis of dot intensity is used to determine the exact level of expression of each gene represented on the array.

How is microarray-based research likely to contribute to therapeutic advances in epilepsy?
The primary application of DNA microarrays in epilepsy research is to evaluate changes in gene expression that are associated with epilepsy. Using experimental epilepsy models in which epilepsy is induced in animals, two kinds of studies are being performed using DNA microarray technologies:

• Broad-scale analysis of gene expression in brain regions that undergo significant structural changes during the development of epilepsy. Researchers hope to identify specific genes that contribute to changes in the brain that may cause seizures when they are inappropriately turned on or off.
• Characterization of the expression of specific gene families within individual cells located in a region of the brain often involved in recurrent seizures. By combining this analysis with studies of the electrical properties of the cell, researchers hope to determine how gene expression may underlie cellular hyperexcitability that contributes to the development of epilepsy.

In sum, DNA microarrays not only make it much easier to investigate genes that have already been identified as being of interest, but also help in identifying new genes that may play fundamental roles in the onset and establishment of spontaneous, recurrent seizures. By gaining this new knowledge, we greatly increase our opportunities to intervene in the seizure process and ultimately to achieve cures for various epileptic disorders.