Study on GIP analogues against the cognitive impairments in APP/PS1 transgenic mice

doi:10.12092/j.issn.1009-2501.2019.07.001

Abstract

Abstract:

AIM: To investigate the neuroprotective effects of DAla2GIP-Glu-PAL on the cognitive impairment in APP/PS1 transgenic mice. METHODS: The nine-month-old male APP/PS1 mice and littermate WT mice were randomly divided into: WT-PBS, APP/PS1-PBS, WT-DAla2GIP-Glu-PAL and APP/PS1-DAla2GIP- Glu-PAL. APP/PS1 and WT mice were injected (i.p.) with PBS (0.01 mol/L) or DAla2GIP-Glu-PAL (5 μmol/L) at a volume of 0.2 mL once a day for 21 days prior to Morris experiments, then immunofluorescence staining, Western blot and ELISA experiments were performed.RESULTS:In Morris water maze test, the escape latency of APP/PS1 transgenic mice was significantly higher than that of WT mice from the 3rd to 5th day (P<0.01). In the probe trails experiment, compared with WT-PBS group mice, the swimming time in the target quadrant of APP/PS1-PBS was significantly decreased (P<0.01). Compared to the APP/PS1-PBS group, there were a significant decrease in the escape latency and an increase in swim time in target quadrant in the APP/PS1-DAla2GIP-Glu-PAL group. The fluorescence intensity of Aβ and GFAP in the hippocampus area of mice was detected by immunofluorescence staining, and the content of Aβ protein in mice was detected by Western blot. The value of APP/PS1-PBS group was significantly higher than that of WT-PBS group (P<0.01), and the value of APP/PBS-DAla2GIP-Glu-PAL group was significantly lower than that of APP/PS1-PBS group (P<0.01). In ELISA experiments, compared with the WT-PBS group, the content of IL-1β and TNF-α in the hippocampus area of the mice were significantly increased, and the content of insulin degrading enzyme was significantly decreased in APP/PS1-PBS group (P<0.01). Compared with the APP/PS1-PBS group, the content of IL-1β and TNF-α were significantly decreased. The content of insulin-degrading enzyme was significantly increased in APP/PBS-DAla2GIP-Glu-PAL group (P<0.01). CONCLUSION: DAla2GIP-Glu- PAL reverses cognitive function damage in APP/PS1 mice by inhibiting Aβ deposition, astrocyte proliferation and inflammatory factor secretion in hippocampus and up-regulating insulin-degrading enzyme content.

Key words: Alzhermer's disease, learning and memory, APP/PS1 transgenic mice, GIP analogues, astrocyte

CLC Number:

YUAN Li, HAN Lingna, CHANG Yongli, ZHANG Cuiying. Study on GIP analogues against the cognitive impairments in APP/PS1 transgenic mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(7): 721-729.

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