Antioxidants have a rapid and long-lasting effect on neuritic abnormalities in APP:PS1 mice.
Senile plaques are a major pathological hallmark of Alzheimer's disease (AD). Compelling evidence suggests that senile plaques lead to structural alterations of neuronal processes and that local toxicity may be mediated by increased oxidative stress. Anti-oxidant therapy can alleviate the neuronal abnormalities in APP mice, but the time-course of this beneficial effect is unknown. We used multiphoton microscopy to assess in vivo the characteristics of antioxidant treatment on senile plaques and neurites in AD model mice (APPswe/PS1dE9). We observed that α-phenyl-N-tert-butyl nitrone (PBN), Ginkgo biloba extract (EGb 761) and Trolox had no effect on the size of existing senile plaques. However, all anti-oxidants had a straightening effect on curved neurites. This effect was detected as soon as 4 days after commencing the treatment, and was maintained after 1 month of daily treatment, with no further increase in the effect. The straightening of neurites persisted 15 days after stopping the treatment. These data indicate that neuronal plasticity is fast and still active in adult animals, and suggest that amelioration of the neuritic distortions associated with senile plaques with antioxidants is both rapid and long lasting.
Garcia-Alloza
Monica
M
Massachusetts General Hospital, Department of Neurology/Alzheimer's Disease Research Laboratory, 114 16th Street, Charlestown, MA 02129, USA.
Borrelli
Laura A
LA
Hyman
Bradley T
BT
Bacskai
Brian J
BJ
D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000235:genetics*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020441:Ginkgo biloba; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D053764:Presenilin-1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D013997:Time Factors; D000096983:Ginkgo Extract
D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D002839:Chromans; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D010936:Plant Extracts; D053764:Presenilin-1; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C029217:phenyl-N-tert-butylnitrone; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid