Antiepileptics Topiramate and Levetiracetam Alleviate Behavioral Deficits and Reduce Neuropathology in APPswe/PS1dE9 Transgenic Mice

BackgroundThe close relationship between epileptic seizure and Alzheimer's disease (AD) has been demonstrated in the past decade. Valproic acid, a traditional first-line antiepileptic drug, exerted protective effects in transgenic models of AD. It remains uncertain whether new antiepileptic drugs could reverse neuropathology and behavioral deficits in AD transgenic mice. AimsAPPswe/PS1dE9 transgenic mice were used in this study, which over express the Swedish mutation of amyloid precursor protein together with presenilin 1 deleted in exon 9. 7-month-old APPswe/PS1dE9 transgenic mice were treated daily with 20mg/kg topiramate (TPM) and 50mg/kg levetiracetam (LEV) for 30days by intraperitoneal injection to explore the effects of TPM and LEV on the neuropathology and behavioral deficits. ResultsThe results indicated that TPM and LEV alleviated behavioral deficits and reduced amyloid plaques in APPswe/PS1dE9 transgenic mice. TPM and LEV increased A clearance and up-regulated A transport and autophagic degradation. TPM and LEV inhibited A generation and suppressed -secretase activity. TPM and LEV inhibited GSK-3 activation and increased the activation of AMPK/Akt activation. Further, TPM and LEV inhibited histone deacetylase activity in vivo. ConclusionsTherefore, TPM and LEV might have the potential to treat AD effectively in patient care.