Soybean-derived phosphatidylinositol inhibits in vivo low concentrations of amyloid beta protein-induced degeneration of hippocampal neurons in V337M human tau-expressing mice.

Abstract

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.

• Authors: Nan-Yan Zhang, Kaori Kitagawa, Naoki Hattori, Yasuhisa Nakayama, Zheng-Mei Xiong, Bo Wu, Bing Liu, Chiyoko Inagaki
• Journal: Life sciences (Life Sci) Vol. 80 Issue 21 Pg. 1971-6 (May 01 2007) ISSN: 0024-3205 [Print] Netherlands
• PMID: 17391709 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Phosphatidylinositols
• tau Proteins

Topics

• Amyloid beta-Peptides (toxicity)
• Analysis of Variance
• Animals
• Hippocampus (drug effects, pathology)
• In Situ Nick-End Labeling
• Mice
• Mice, Transgenic
• Mutation (genetics)
• Neurons (drug effects)
• Phosphatidylinositols (pharmacology)
• Soybeans (chemistry)
• tau Proteins (genetics)