Microarray expression profiling
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Microarray or gene chip analyses are largescale studies of changes in gene expression (i.e., in the amount of gene product produced). It allows the collection of information about genetic changes that occur together in a coordinated fashion to affect a given phenotype, rather than being limited to the examination of one gene at a time. For example, alcoholics often exhibit loss of white matter in various brain regions. This white matter is composed of the extensions of nerve cells that are normally covered by the insulating substance myelin. Using mRNA expression profiling, reduced expression of several myelinrelated genes could be demonstrated in the brain tissue of alcoholics obtained after they died. Microarrays thus allow for a molecular or "genomic" approach to neurobiology because of their capacity to assess widespread changes in gene expression. Microarrays permit a more global view of the system being studied than typical bench laboratory techniques and require new analytic and computational approaches. Despite considerable promise, numerous technical and experimental design issues need to be considered in every array experiment. |
A second example: neuronal plasticity of the brain dopamine system is thought to underlie the behavioral changes elicited by chronic exposure to drugs of abuse such as cocaine. To identify the potential mechanisms responsible for these adaptive changes, three genetically distinct mouse models of altered dopaminergic function have been used. These genetic animal models that recapitulate the pharmacological models of "behavioral sensitization" associated with exposure to psychostimulants (dopamine transporter knockout; DATKO); tricyclic antidepressants (norepinephrine transporter knockout, NETKO) and reserpine (vesicular monoamine transporter knockout, VMAT2+/-), all demonstrate enhanced behavioral responses to direct or indirect dopamine receptor agonists.
By microarray expression profiling of 36,000 genes/ESTs (expressed sequence tags), a handful of commonly up- and down-regulated genes in the striatum of the three mutant lines was identified. Comparison of this profile with that of normal mice pharmacologically sensitized to cocaine, further restricted this collection to only two down-regulated genes, giving insight into a possible general mechanism underlying drug-induced neuronal and behavioral plasticity.
See also under "Molecular biological research methodology": Microarray analysis