Soybean-derived phosphatidylinositol inhibits in vivo low concentrations of amyloid β 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 (≤ 10 nM) of amyloid β proteins (Aβs) showed neurotoxicity via a phosphatidylinositol metabolism disorder, and soybean-derived phosphatidylinositol protected the neurons against the Aβ's neurotoxicity. In the present study, such a neurotoxic effect of Aβ and a neuroprotective effect of phosphatidylinositol were examined in vivo using transgenic mice expressing V337 M human tau. Intrahippocampal CA1 injection of 1.5 μl of 100 nM or 1 μM Aβ25–35 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 Aβ at lower concentrations after diffusion. Intrahippocampal co-injection or intracerebroventricular administration of 1.5 μl of 500 nM phosphatidylinositol prevented the Aβ25–35-induced neuronal degeneration in all the hippocampal regions, while co-injection of another acidic phospholipid, phosphatidylserine (1.5 μl, 500 nM) with Aβ25–35 showed no protective effects. Thus, exogenously applied phosphatidylinositol appeared to minimize the toxic effects of Aβ in vivo. These results suggest that soybean-derived phosphatidylinositol may be effective in the treatment of Alzheimer's disease.