Aniracetam restores the effects of amyloid-beta protein or ageing on membrane fluidity and intracellular calcium concentration in mice synaptosomes.
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.
Li
Y
Y
College of Life Sciences, Qufu Normal University, Qufu, PR China.
Wang
J-J
JJ
Cai
J-X
JX
D000375:Aging / Q000502:physiology*; D000465:Algorithms; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000187:drug effects*; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D018697:Nootropic Agents; D011760:Pyrrolidinones; C036466:aniracetam; D002118:Calcium