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

Authors :
Song F
Liu T
Meng S
Li F
Zhang Y
Jiang L
Source :
Journal of molecular neuroscience : MN [J Mol Neurosci] 2018 Dec; Vol. 66 (4), pp. 595-603. Date of Electronic Publication: 2018 Nov 09.
Publication Year :
2018

Abstract

To examine the effect of subcutaneous injection of insulin-like growth factor-1 (IGF-1) on the expression of the amyloid protein (Aβ <subscript>1-40</subscript> ), 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 (50 μg/kg day) was administered once daily to the wild-type therapy group and transgenic therapy group for 8 weeks, respectively. The expression of the Aβ <subscript>1-40</subscript> in the cortex and hippocampus was detected by immunohistochemistry 8 weeks after administration. The levels of Aβ <subscript>1-40</subscript> , DAM10, BACE1, and PS1 were analysed by Western blot. The expression of the Aβ <subscript>1-40</subscript> 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 Aβ <subscript>1-40</subscript> over-expression in the cortex and hippocampus and might inhibit the damage induced by Aβ <subscript>1-40</subscript> 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.

Details

Language :
English
ISSN :
1559-1166
Volume :
66
Issue :
4
Database :
MEDLINE
Journal :
Journal of molecular neuroscience : MN
Publication Type :
Academic Journal
Accession number :
30414017
Full Text :
https://doi.org/10.1007/s12031-018-1201-4