In the present study, we observed the in vitro effect of
aniracetam on membrane fluidity and free
calcium concentrations ([Ca(2+)]i) of frontal cortical (FC) and hippocampal (HP) synaptosomes of aged mice and young mice treated with
amyloid-beta protein (Abeta) Membrane fluidity was measured by using fluorescence anisotropy of the lipophilic probe,
1,6-diphenyl-1,3,5-hexatriene (DPH). [Ca(2+)]i was measured by using Fura 2-AM fluorescent spectrophotometry. We found that membrane fluidity of the FC and HP synaptosomes was decreased in 14 months old mice compared with that in 3 months old mice. Similarly,
Abeta25-35 (1 microM) decreased the membrane fluidity in 3 months old mice. These effects of ageing and
Abeta25-35 on membrane fluidity were restored by
aniracetam in a concentration-dependent manner. Furthermore,
Abeta25-35 (1 microM) largely increased [Ca(2+)]i in FC and HP synaptosomes in 3 months old mice, but this effect on HP synaptosomes was effectively reversed by
aniracetam (1-4 mM). The present findings suggest that
aniracetam restores age- and Abeta-induced alterations in membrane fluidity or Abeta-induced increase in [Ca(2+)]i, demonstrating a possible beneficial role of
aniracetam in the clinic treatment for
senile dementia or
Alzheimer's disease.