title: Antiepileptics topiramate and levetiracetam alleviate behavioral deficits and reduce neuropathology in APPswe/PS1dE9 transgenic mice.
abstract: BACKGROUND
  The 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.
  
  
  OBJECTIVE
  APPswe/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 20 mg/kg topiramate (TPM) and 50 mg/kg levetiracetam (LEV) for 30 days by intraperitoneal injection to explore the effects of TPM and LEV on the neuropathology and behavioral deficits.
  
  
  RESULTS
  The results indicated that TPM and LEV alleviated behavioral deficits and reduced amyloid plaques in APPswe/PS1dE9 transgenic mice. TPM and LEV increased Aβ clearance and up-regulated Aβ transport and autophagic degradation. TPM and LEV inhibited Aβ generation and suppressed γ-secretase activity. TPM and LEV inhibited GSK-3β activation and increased the activation of AMPK/Akt activation. Further, TPM and LEV inhibited histone deacetylase activity in vivo.
  
  
  CONCLUSIONS
  Therefore, TPM and LEV might have the potential to treat AD effectively in patient care.
authors.affiliation: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Jian-Quan
authors.initials: JQ
authors.lastname: Shi
authors.forename: Bian-Rong
authors.initials: BR
authors.lastname: Wang
authors.forename: You-Yong
authors.initials: YY
authors.lastname: Tian
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Zhao
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Xie
authors.forename: Ying-Dong
authors.initials: YD
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000077287:Levetiracetam; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D053764:Presenilin-1 / Q000235:genetics; D000077236:Topiramate
chemical_list: D016564:Amyloid beta-Protein Precursor; D000927:Anticonvulsants; D018696:Neuroprotective Agents; D053764:Presenilin-1; D000077236:Topiramate; D005632:Fructose; D000077287:Levetiracetam; D010889:Piracetam
keywords: Alzheimer's disease; Behavior; Histone deacetylase inhibition; Levetiracetam; Neuropathology; Topiramate
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