Soybean-derived phosphatidylinositol inhibits in vivo low concentrations of amyloid beta protein-induced degeneration of hippocampal neurons in V337M human tau-expressing mice.
In our previous reports using primary cultured rat hippocampal neurons, pathophysiological concentrations (< or =10 nM) of amyloid beta proteins (Abetas) showed neurotoxicity via a phosphatidylinositol metabolism disorder, and soybean-derived phosphatidylinositol protected the neurons against the Abeta's neurotoxicity. In the present study, such a neurotoxic effect of Abeta and a neuroprotective effect of phosphatidylinositol were examined in vivo using transgenic mice expressing V337 M human tau. Intrahippocampal CA1 injection of 1.5 mul of 100 nM or 1 microM Abeta25-35 increased the number of degenerating neurons with an apoptotic feature in bilateral hippocampal CA1, CA2, CA3 and dentate gyrus regions in 1 month, demonstrating an in vivo neurotoxic effect of Abeta at lower concentrations after diffusion. Intrahippocampal co-injection or intracerebroventricular administration of 1.5 microl of 500 nM phosphatidylinositol prevented the Abeta25-35-induced neuronal degeneration in all the hippocampal regions, while co-injection of another acidic phospholipid, phosphatidylserine (1.5 microl, 500 nM) with Abeta25-35 showed no protective effects. Thus, exogenously applied phosphatidylinositol appeared to minimize the toxic effects of Abeta in vivo. These results suggest that soybean-derived phosphatidylinositol may be effective in the treatment of Alzheimer's disease.
Zhang
Nan-Yan
NY
Department of Pharmacology, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Kitagawa
Kaori
K
Hattori
Naoki
N
Nakayama
Yasuhisa
Y
Xiong
Zheng-Mei
ZM
Wu
Bo
B
Liu
Bing
B
Inagaki
Chiyoko
C
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects*; D010716:Phosphatidylinositols / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry*; D016875:tau Proteins / Q000235:genetics*
D016229:Amyloid beta-Peptides; D010716:Phosphatidylinositols; D016875:tau Proteins