| First Author | van Loo KM | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8688 | PubMed ID | 26498180 |
| Mgi Jnum | J:227916 | Mgi Id | MGI:5704005 |
| Doi | 10.1038/ncomms9688 | Citation | van Loo KM, et al. (2015) Zinc regulates a key transcriptional pathway for epileptogenesis via metal-regulatory transcription factor 1. Nat Commun 6:8688 |
| abstractText | Temporal lobe epilepsy (TLE) is the most common focal seizure disorder in adults. In many patients, transient brain insults, including status epilepticus (SE), are followed by a latent period of epileptogenesis, preceding the emergence of clinical seizures. In experimental animals, transcriptional upregulation of CaV3.2 T-type Ca(2+)-channels, resulting in an increased propensity for burst discharges of hippocampal neurons, is an important trigger for epileptogenesis. Here we provide evidence that the metal-regulatory transcription factor 1 (MTF1) mediates the increase of CaV3.2 mRNA and intrinsic excitability consequent to a rise in intracellular Zn(2+) that is associated with SE. Adeno-associated viral (rAAV) transfer of MTF1 into murine hippocampi leads to increased CaV3.2 mRNA. Conversely, rAAV-mediated expression of a dominant-negative MTF1 abolishes SE-induced CaV3.2 mRNA upregulation and attenuates epileptogenesis. Finally, data from resected human hippocampi surgically treated for pharmacoresistant TLE support the Zn(2+)-MTF1-CaV3.2 cascade, thus providing new vistas for preventing and treating TLE. |
