Single-cell molecular biology: implications for the diagnosis and treatment of neurological disease

The normal functioning of the central nervous system (CNS) requires complex interactions among numerous biological components. The pathophysiology of perturbations in this system is as complex as that of neurological disease. Many methods exist to examine the biological output of dysfunctional cells from a diseased system (e.g., immunohistochemical analysis, electrophysiology, and microdialysis), with one goal being to understand the mechanisms of cell death. This understanding may allow the design of therapeutic strategies to prevent cell death and ensuing behavioral abnormalities. Analysis of messenger RNA (mRNA) levels for various genes in CNS tissue may enhance understanding of neurological disease, since cells differ in the complement and abundance of genes they express. One popular method for detecting changes in gene expression is the Northern blot technique, in which total RNA from a sample is extracted and the RNA molecules are separated by size on a denaturing gel and transferred or "blotted" onto nylon membranes that are then probed with radiolabeled DNA for subsequent autoradiograpic detection of gene expression.