Referenced in: none

Automatically associated channels: Cav3.2

Title: Zinc regulates a key transcriptional pathway for epileptogenesis via metal-regulatory transcription factor 1.

Authors: Karen M J van Loo, Christina Schaub, Julika Pitsch, Rebecca Kulbida, Thoralf Opitz, Dana Ekstein, Adam Dalal, Horst Urbach, Heinz Beck, Yoel Yaari, Susanne Schoch, Albert J Becker

Journal, date & volume: Nat Commun, 2015 , 6, 8688

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26498180

Abstract
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.