Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer's Disease Mouse Model

J Alzheimers Dis. 2016;51(2):333-8. doi: 10.3233/JAD-151078.

Abstract

The aim of this study was to examine hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer's disease mouse model using cilostazol as a chemical stimulus. Eight-month-old mice were assigned to vehicle or cilostazol treatment for three months and hemispheres were analyzed using quantitative proteomics. Bioinformatics interpretation showed that following treatment, aggregation of blood platelets significantly decreased in the right hemisphere whereas neurodegeneration significantly decreased and synaptic transmission increased in the left hemisphere only. Our study provides novel evidence on cerebral laterality of pharmacologic activity, with important implications in deciphering regional pharmacodynamic effects of existing drugs thus uncovering novel hemisphere-specific therapeutic targets.

Keywords: Alzheimer’s disease; cilostazol; hemisphere asymmetry; mass spectrometry pharmacology; pharmacodynamics; pharmacoproteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism*
  • Cilostazol
  • Disease Models, Animal
  • Functional Laterality / drug effects
  • Male
  • Mice, Transgenic
  • Nootropic Agents / pharmacokinetics
  • Nootropic Agents / pharmacology*
  • Proteome / drug effects
  • Tetrazoles / pharmacokinetics
  • Tetrazoles / pharmacology*

Substances

  • Nootropic Agents
  • Proteome
  • Tetrazoles
  • Cilostazol