Cellular and Molecular Neurobiology
Author: Estefania Clavenzani | Email: eclavenzani@immf.uncor.edu
E Clavenzani1°, J M Bourbotte, J C Battista, C Conde1°
1° Estefania Clavenzani
Neuroinflammation is an important mechanism of hyperexcitable pathologic brain tissue in pharmaco- resistant epilepsies. The transforming growth factor β (TGF-β) pathway is involved in epileptogenesis and SARA (Smad Anchor for Receptor Activation) is a protein associated to TGF-β. A recent study has reported that the expression of SARA is increased in the hippocampus and temporal cortex of rats induced to status epilepticus (SE) with pilocarpine, and also in patients with temporal lobe epilepsy (TLE). Smurf2 is a ubiquitin ligase contributing to physiological and pathological processes, which has been involved in the degradation of SARA and TGF-β receptors, in HEK293T cells. However, studies don’t show a cooperative modulation between SARA and Smurf2 proteins, not even Smurf2 activity in TLE conditions. Then, in this work we focus on the biological role of SARA in TLE and its possible participation in seizures. We induced SE on young rats with pilocarpine, to analyze levels and distribution of SARA and Smurf2 in neurons. Additionally, in the same way, we analyzed the behavior of both proteins in samples from human astrocytes of epileptic versus healthy patients. Our preliminary results show an increased expression of SARA in human astrocytes and animal models with TLE vs control samples. These findings could indicate a deregulation in the complex formed by Smurf2, leading to the SARA and TGF-β receptor accumulation and could be a reason for seizures in patients.