Collapsin Response Mediator Protein 2, a Potential Therapeutic Target in Temporal Lobe Epilepsy

Аннотация

Temporal lobe epilepsy (TLE) is the most prevalent subtype of epilepsy in humans and can easily develop into refractory epilepsy. The development of TLE is a complex process involving acute insults, a latent period, and chronic recurrent seizures. The latent period could provide an opportunity for intervention if molecular targets were to be identified. Collapsin response mediator protein 2 (CRMP2) was recently found to be involved in the mechanism of epileptogenesis. However, the results were inconsistent. We aimed to determine if CRMP2 is differentially expressed in rats following status epilepticus (SE), and to validate the expression of CRMP2 during the latent period. We used kainic acid (KA) as the initial insult to induce SE in rats and applied two-dimensional gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MALDI-TOF/TOF) to search for aberrant protein expression in the hippocampus. Western blots were used to confirm the expression level of proteins. Protein extracts of the hippocampus from the sham and the KA groups were separated by 2D-DIGE; 17 protein spots on the gel, representing 10 unique proteins, were found to be significantly different between the KA and sham groups. Among those, CRMP2 was significantly up-regulated. Results of western blot analysis confirmed the increased CRMP2 levels in the KA group. Our findings indicate that the increase in CRMP2 during the latent period is possibly involved in the mechanism of epileptogenesis and is expected to be a novel therapeutic target.