Global expression profiling in epileptogenesis: does it add to the confusion?

Abstract

Since the inception of global gene expression profiling platforms in the mid-1990s, there has been a significant increase in publications of differentially expressed genes in the process of epileptogenesis. In particular for mesial temporal lobe epilepsy, the presence of a latency period between the first manifestation of seizures to chronic epilepsy provides the opportunity for therapeutic interventions at the molecular biology level. Using global expression profiling techniques, approximately 2000 genes have been published demonstrating differential expression in mesial temporal epilepsy. The majority of these changes, however, are specific to laboratory or experimental conditions with only 53 genes demonstrating changes in more than two publications. To this end, we review the current status of gene expression profiling in epileptogenesis and suggest standard guidelines to be followed for greater accuracy and reproducibility of results.

Figure 1

Initial hit theory of epileptogenesis. Abbreviations: AED = anti‐epileptic drug.

Figure 2

(L‐top) Low power (2.5×) view demonstrating normal subiculum into CA1; (R‐top) Low power (2.5×) view demonstrating CA1 sclerosis and sparing of CA2; (L‐bottom) Low power (2.5×) view demonstrating neuronal loss in CA3/4; (R‐bottom) Medium power (5×) view with dispersion of dentate gyrus. (arrow: subiculum, block arrow: CA1, curved block arrow: CA2, curved arrow: CA3/4, arrow outline: dentate gyrus).

Figure 3

Global expression profiling experiments. Abbreviations: qRT‐PCR = quantitative real‐time polymerase chain reaction.