Effect of amylin on learning and memory abilities and Akt signaling pathway in mice with Alzheimer's disease

Abstract

Objective To investigate the effects of amylin, also known as islet amyloid polypeptide (IAPP), on learning and memory abilities and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in APP/PS1 mice. Methods A total of 20 APP/PS1 mice were randomly divided into Alzheimer's disease (AD) group and IAPP group, with 10 mice in each group. The mice in the latter group were given an intraperitoneal injection of 0.5 μmol/L IAPP, and those of the former group received same dose of PBS. Both interventions were given once per day, for 10 weeks. Morris water maze test was used to measure the learning and memory abilities; HE staining was employed to observe the pathological changes in the hippocampus; Transmission electron microscopy was utilized to observe the ultrastructure of hippocampal neurons; Biochemical assay were conducted to detect the contents of glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and superoxide dismutase (SOD) in hippocampal tissues; ELISA was applied to measure the levels of inflammatory factors such as IL-1β, IL-6, and TNF-α as well as content of Aβ42 in hippocampal tissues; And Western blotting was conducted to detect the expression of PI3K/Akt proteins. Results Compared with the AD group, significantly shorter platform latency (P < 0.01), increased number of traversing the platform and longer time to explore the hidden platform (P < 0.01) were observed in the IAPP group, but no such difference was seen in the swimming speed of the mice. HE staining displayed that the IAPP group had more and well-arranged nerve cells in the hippocampal tissue when compared with the AD group (P < 0.05). Lower Aβ protein expression (P < 0.01), reduced oxidative stress and decreased contents of inflammatory factors (P < 0.01) in hippocampal tissue were observed in the IAPP group than the AD group. The IAPP group showed clearer structure of neuronal mitochondria, reduced vacuolization, and better arranged microtubules and microfilaments, and elevated expression of p-PI3K/PI3K and p-Akt/Akt proteins when compared with the AD group (P < 0.01). Conclusion Amylin can reduce oxidative stress and inflammatory responses, improve learning and memory abilities in AD mice, and promote the activity of PI3K/Akt signaling pathway.

Keywords

• alzheimer's disease
• amylin
• pi3k/akt pathway
• oxidative stress
• inflammatory level