Expression and Cellular Distribution of Major Vault Protein: A Putative Marker for Pharmacoresistance in a Rat Model for Temporal Lobe Epilepsy

Summary: Purpose: Because drug transporters might play a role in the development of multidrug resistance (MDR), we investigated the expression of a vesicular drug transporter, the major vault protein (MVP), in a rat model for temporal lobe epilepsy.

Methods: By using real-time polymerase chain reaction (PCR) analysis and immunocytochemistry, we quantified MVP mRNA and protein from the dentate gyrus (DG) and parahippocampal cortex (PHC) taken from EEG-monitored rats at 1 week after electrically induced status epilepticus (SE) and at 5–9 months after SE, when rats exhibit spontaneous seizures.

Results: Within 1 week after SE, MVP mRNA levels increased in both DG and PHC compared with those in controls. In chronic epileptic rats, MVP mRNA was still significantly upregulated in the PHC, whereas in the DG, the expression returned to control levels. MVP protein increased within 1 day after SE in reactive microglial cells within most limbic regions; the hippocampus showed the highest expression at 1 week after SE. In chronic epileptic rats, MVP protein expression was largely decreased in most brain regions, but it was still high, especially in the piriform cortex. The occurrence of SE was a prerequisite for increased MVP expression, because no increase was found in electrically stimulated rats that did not exhibit SE.

Conclusions: MVP expression is upregulated in chronic epileptic rats and may contribute to the development of pharmacoresistance.