Laser microdissection and gene expression profiling in the human postmortem brain

Laser microdissection in combination with gene expression profiling using postmortem human brain tissue provides a powerful approach to interrogating cell type-specific pathologies within neural circuits that are known to be dysfunctional in neuropsychiatric disorders. The success of these experiments critically depends on a number of factors, such as the cellular purity of the sample, the quality of the RNA, the methodologies of data normalization and computational data analysis, and how data are interpreted. Data obtained from these experiments should be validated at the protein level. Furthermore, from the perspective of disease mechanism discovery, it would be ideal to investigate whether manipulation of the expression of genes identified as differentially expressed can rescue or ameliorate the neurobiologic or behavioral phenotypes associated with the specific disease. Thus, the ultimate value of this approach rests upon the fact that the generation of novel disease-related pathophysiologic hypotheses may lead to deeper understanding of disease mechanisms and possible development of effective targeted treatments.