Amelioration of Behavioral Impairments and Neuropathology by Antiepileptic Drug Topiramate in a Transgenic Alzheimer's Disease Model Mice, APP/PS1

Int J Mol Sci. 2019 Jun 19;20(12):3003. doi: 10.3390/ijms20123003.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that is the main cause of dementia in the elderly. The aggregation of β-amyloid peptides is one of the characterizing pathological changes of AD. Topiramate is an antiepileptic drug, which in addition, is used in the treatment of many neuropsychiatric disorders. In this study, the therapeutic effects of topiramate were investigated in a transgenic mouse model of cerebral amyloidosis (APP/PS1 mice). Before, during, and after topiramate treatment, behavioral tests were performed. Following a treatment period of 21 days, topiramate significantly ameliorated deficits in nest-constructing capability as well as in social interaction. Thereafter, brain sections of mice were analyzed, and a significant attenuation of microglial activation as well as β-amyloid deposition was observed in sections from topiramate-treated APP/PS1 mice. Therefore, topiramate could be considered as a promising drug in the treatment of human AD.

Keywords: APP/PS1 transgenic mouse; Alzheimer’s disease; amyloidosis; topiramate.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Amyloidosis / drug therapy
  • Amyloidosis / pathology
  • Animals
  • Anticonvulsants / chemistry
  • Anticonvulsants / pharmacology*
  • Behavior, Animal / drug effects*
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Transgenic
  • Molecular Structure
  • Protein Aggregates / drug effects
  • Protein Aggregation, Pathological / drug therapy
  • Protein Aggregation, Pathological / metabolism
  • Topiramate / chemistry
  • Topiramate / pharmacology*

Substances

  • Amyloid beta-Protein Precursor
  • Anticonvulsants
  • Protein Aggregates
  • Topiramate