Insulin-Like Growth Factor-1 Alleviates Expression of A(1-40) and -, -, and -Secretases in the Cortex and Hippocampus of APP/PS1 Double Transgenic Mice

摘要

To examine the effect of subcutaneous injection of insulin-like growth factor-1 (IGF-1) on the expression of the amyloid protein (A(1-40)), -secretase (ADAM10), -secretase (BACE1), and -secretase (PS1) in APP/PS1 double transgenic mice. APP/PS1 double transgenic mice and wild-type mice were divided into wild-type group, wild-type therapy group, transgenome group, and transgenic therapy group. Subcutaneous injection of IGF-1 (50g/kgday) was administered once daily to the wild-type therapy group and transgenic therapy group for 8weeks, respectively. The expression of the A(1-40) in the cortex and hippocampus was detected by immunohistochemistry 8weeks after administration. The levels of A(1-40), DAM10, BACE1, and PS1 were analysed by Western blot. The expression of the A(1-40) in the cortex of the gene therapy group was significantly lower than that of the transgenome group (p0.05). In APP/PS1 double transgenic mice, BACE1 expression was markedly higher in both the hippocampus (p0.001, p=0.00009) and the cortex (p=0.001), compared to that of the wild-type mice. The treatment of IGF-1 markedly reduced ADAM10 expression in the hippocampus in both transgenic mice and wild-type mice (p0.05), whereas the treatment mainly decreased BACE1 expression in transgenic mice but not in the wild-type mice (p0.05). No significant differences in PS1 levels were detected in all groups. IGF decreased A(1-40) over-expression in the cortex and hippocampus and might inhibit the damage induced by A(1-40) in APP/PS1 double transgenic mice. Our study suggests that IGF-1 should inhibit A production through -secretase and -secretase but not -secretase.