Abstracts

Rationale: Recent studies have shown that epileptic seizures can exhibit pathophysiological processes such as cognitive impairment similar to Alzheimer's Disease (AD). Additionally, different degrees of memory problems, language and of executive functions can occur in patients with epilepsy. Despite many studies on the association between epilepsy and AD, their mechanisms and neurobiological bases is still unclear. In this study we investigated the markers of AD in a model of epilepsy and comorbidities, the Wistar Audiogênic Rat (WAR) strain. Methods: We used 2 years old animals divided into 4 groups: (1) Wistar submitted to no stimulus (WT2-NS); (2) WAR submitted to no stimulus (WAR2-NS); (3) WAR submitted to 28 audiogenic stimuli with 2 years old (WAR2-28S) and (4) WAR submitted to 28 audiogenic stimuli with 3 months old (WAR3m-28S). 3 months old WAR submitted to no stimulus was used as control of the experiments. We conducted immunohistochemistry for β-amyloid and phospo-tau (S396) in accordance with manufacturer protocols. β-amyloid and phospho-tau (S396) levels were assessed by Western blotting in hippocampal samples. Approved by Ethics Comittee (protocol number: 002/2011). Results: The levels of β-amyloid into the 4 groups of senescent animals presented no difference, however preliminary data in WAR with 3 months old showed about 50% decrease of β-amyloid levels when compared to 2 years old animals (Wistar and WAR). These preliminary data suggest a possible regulation of β-amyloid in the WAR strain, that we could not demonstrate in 2 years old animals, since at this age the Wistar rats (WT2-NS) exhibited high β-amyloid deposition, similar to the epileptic rats. For phospho-tau analysis, we found that phosphorylation levels were up-regulated 1.5 fold in WAR2-NS and WAR2-28S, but interestingly the WAR3m-28S showed no difference in the regulation when compared to WT2-NS and significant decrease in the phosphorylation when compared to WAR2-NS and WAR2-28S. Moreover, in preliminary results, the phospho-tau level was up-regulated in 2 years old WAR when compared to the 4 groups of 2 years old animals. These results suggest that WAR strain exhibit an intrinsic increased tau phosphorylation and that, when WAR were submitted to epileptic seizures at young age this was associated to a decrease of the tau phosphorylation in senescence. Conclusions: In summary, we report for the first time, the possible association between epilepsy and AD in the WAR strain, a genetic model of epilepsy. Furthermore, early epileptic seizures were able to decrease the tau phophorylation in the senescence. Thus, plastic phenomena associated to the establishment of the epilepsy can represent neuroprotection mechanisms for the onset of AD physiopathology in this model. Financial support: FAPESP, Cinapce-FAPESP, Capes-PROEX, CNPq, FAEPA.