Figure 7.

Role of SphK2 activity in AD brains. A, Effect of the direct injection of SKI II into the hippocampus of nontransgenic wild-type female mice (C57BL) at 8 weeks of age. The levels of Tris-soluble Aβ in the injected side of hippocampus were divided by those in the uninjected side. Data represent relative ratio of each group (n = 4; mean ± SEM; **p < 0.01). B, Levels of Tris-soluble Aβ in the cerebral cortices of female A7 mice at 6 months of age after a 7 d treatment with SKI II (50 mg · kg⁻¹ · d⁻¹, p.o.). Total brain Aβ levels were measured by human-specific sandwich ELISA (n = 5; mean ± SEM; **p < 0.01). C, Effect of Aβ fibril on SphK2 activity in N2a cells. N2a cells were treated with Aβ₄₂ fibril (30 μm) overnight, and cell lysates were subjected to an in vitro SphK2 activity assay (n = 3; mean ± SEM; ***p < 0.001). D–F, Immunoblot analysis of Tris-soluble fractions (15 μg of protein in each lane) from cortices of AD (denoted as A) or non-demented (denoted as N) individuals. Average protein levels of SphK2 (E) and βIII-tubulin (F) in each individual were analyzed by densitometric analyses (*p < 0.05). G, Average of in vitro SphK2 enzymatic activity of Tris-soluble fractions from brains of AD and non-demented individuals. The enzymatic activities of SphK2 were normalized by the protein levels of SphK2 quantified in D.