Abstract
We aim to study the therapeutic efficacy of analog P165 of amyloid precursor protein 5-mer peptide in streptozotocin (STZ)-induced cognitive decline model. Rats were divided into four groups: control, STZ, STZ+P165, and STZ+rosiglitazone (RSG). STZ model was established by intracerebroventricular injection of STZ. Three weeks following surgery, rats received daily gavage administration of distilled water (control and STZ groups), P165 (STZ+P165), or RSG (STZ+RSG) for four consecutive weeks. Learning and memory abilities were assessed with the Morris water maze test. Insulin-like growth factor-1 (IGF-1) was detected by ELISA. Expressions of insulin receptor-β (IR-β), insulin receptor substrate-1 (IRS-1), serine/threonine kinase (Akt), and phosphorylation of CREB (p-CREB) were observed by immunohistochemistry. Both P165 and RSG significantly reduced the escape latency relative to the STZ group (P165, P < 0.05; RSG, P < 0.01). STZ model rats had reduced levels of IGF-1 relative to control, and this deficit was attenuated in the STZ+P165 group (P < 0.01). IR and IRS-1 were elevated in STZ rats, and these levels were restored to near control in the STZ+P165 and STZ+RSG groups (P < 0.01). Our findings demonstrate that P165 and RSG improved hippocampus-dependent spatial learning and memory in STZ rats by regulating the insulin signaling pathway.
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Acknowledgments
This work was supported by the following grants: Beijing Natural Science Foundation (7132044), Capital Health Development Research Fund (2011-1001-02), Beijing Health Systems, Health and Technical Personnel of High-level Plan (2009-3-64).
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Supplementary Figure S1. Histological examination of hippocampal CA1 and CA3 neurons from different groups. Sections were stained with HE. Magnification, 100X. (PDF 332 kb)
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Xu, BL., Wang, R., Meng, XH. et al. Effects of analog P165 of amyloid precursor protein 5-mer peptide on learning, memory and brain insulin receptors in the rat model of cognitive decline. Neurol Sci 35, 1821–1826 (2014). https://doi.org/10.1007/s10072-014-1849-7
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DOI: https://doi.org/10.1007/s10072-014-1849-7