Insulin-Like Growth Factor-1 Alleviates Expression of Aβ1-40 and α-, β-, and γ-Secretases in the Cortex and Hippocampus of APP/PS1 Double Transgenic Mice.

Abstract

To examine the effect of subcutaneous injection of insulin-like growth factor-1 (IGF-1) on the expression of the amyloid protein (Aβ1-40), α-secretase (ADAM10), β-secretase (BACE1), and γ-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 (50μg/kgday) was administered once daily to the wild-type therapy group and transgenic therapy group for 8weeks, respectively. The expression of the Aβ1-40 in the cortex and hippocampus was detected by immunohistochemistry 8weeks after administration. The levels of Aβ1-40, DAM10, BACE1, and PS1 were analysed by Western blot. The expression of the Aβ1-40 in the cortex of the gene therapy group was significantly lower than that of the transgenome group (p < 0.05). In APP/PS1 double transgenic mice, BACE1 expression was markedly higher in both the hippocampus (p < 0.001, 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 (p < 0.05), whereas the treatment mainly decreased BACE1 expression in transgenic mice but not in the wild-type mice (p < 0.05). No significant differences in PS1 levels were detected in all groups. IGF decreased Aβ1-40 over-expression in the cortex and hippocampus and might inhibit the damage induced by Aβ1-40 in APP/PS1 double transgenic mice. Our study suggests that IGF-1 should inhibit Aβ production through α-secretase and β-secretase but not γ-secretase.