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 (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 Aβ1–40 in the cortex and hippocampus was detected by immunohistochemistry 8 weeks 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.
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Acknowledgements
I wish to thank Zongyan Teng for her suggestions on experimental design and thank Xaioyi Yao for providing timely assistance in analysing a large number of samples.
Funding
This work was supported by the following grants: Funds for Young Scholar of the Second Affiliated Hospital of Harbin Medical University (No. QN2012-08) (the leading researcher of the project group: Fangfang Song) and the Scientific Research Foundation for the Returned Overseas Scholars of Heilongjiang Province (No. LC2009C13) (the leading researcher of the project group: Lihong Jiang).
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Yina Zhang is responsible for the design and writing of the project. Lihong Jiang is responsible for project funding, design, and analysis with constructive discussions. Fangfang Song is responsible for project funding and completing the whole experiment and is the author of the first draft of the article. Tingting Liu contributed significantly to manuscript modification and embellishment. Songyan Meng contributed to proofread data and modify charts. Fengqing Li performed the figures’ typesetting.
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Song, F., Liu, T., Meng, S. et al. 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. J Mol Neurosci 66, 595–603 (2018). https://doi.org/10.1007/s12031-018-1201-4
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DOI: https://doi.org/10.1007/s12031-018-1201-4