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

CNS Neuroscience and Therapeutics - Tập 19 Số 11 - Trang 871-881 - 2013
Jian‐Quan Shi1, Bian‐Rong Wang2, You‐Yong Tian1, Jun Xu3, Li Gao3, Shuli Zhao4, Teng Jiang1, Hong‐Guang Xie4, Yingdong Zhang1
1Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
2Department of Neurology Jiangsu Geriatric Hospital Nanjing Jiangsu Province China
3Department of Neurology Affiliated Nanjing Brain Hospital Nanjing Medical University Nanjing Jiangsu Province China
4Central Laboratory Nanjing First Hospital Nanjing Medical University Nanjing Jiangsu Province China

Tóm tắt

SummaryBackgroundThe 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 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.ResultsThe 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.ConclusionsTherefore, TPM and LEV might have the potential to treat AD effectively in patient care.

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Thông tin xuất bản

CNS Neuroscience and Therapeutics

Tập 19 Số 11

871-881

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