Deficiency of FPR2 improves learning and attenuates tau hyperphosphorylation in ICV-STZ Alzheimer's disease mouse model

[Speaker] Yang Yu:1
[Co-author] Ding Wang:1, Haibo Zhang:1
1:School of Pharmacy, Shanghai Jiao Tong University, China

Background: Alzheimer's disease (AD) is a neurodegenerative disease. AD has two main pathological hallmarks, senile plaques, which consist of beta-amyloid protein (Abeta), and neurofibrillary tangles (NFTs), which consist of hyperphosphorylated tau protein. Formyl peptide receptor 2 (FPR2) is a G protein-coupled receptor (GPCR), which mainly expressed on the surface of macrophages in mammals. Studies showed that FPR2 also expressed on the surface of microglial cells and astrocytes in the brain. FPR2 is one of the functional receptor of Abeta. However, the function of FPR2 on tau protein is poorly understood. In this study, we examined the effect of FPR2 on mouse learning and memory and phosphorylation of tau protein in an AD mouse model. Methods: We established the ICV-STZ (intracerebroventricular injection of Streptozotocin) mouse model of AD by used FPR2 knock-out (FPR2-/-) mice and wide type mice. We used Morris water maze test to detect the learning and memory of mice, and western blot experiment to examine the phosphorylation level of tau protein. Results: The results of Morris water maze tests showed that, for the wide-type mice, the ICV-STZ AD mice took a longer time and swam a longer distance than ICV-saline control mice. This results suggested that learning ability was impaired in ICV-STZ AD mice compared with ICV-saline control mice. While for FPR2-/- mice, deficiency of FPR2 improved the learning ability of ICV-STZ AD mice, as evidenced by significant shorter escape latency and swimming distance to reach the escape platform compared with ICV-STZ wide type AD mice. We further detected phosphorylation level of tau protein in the hippocampus of the mice brain. For wide type mice, the phosphorylated tau protein was significantly increased in ICV-STZ AD model mice compared with ICV-saline control mice. However, for FPR2-/- mice, deficiency of FPR attenuated tau hyperphosphorylation in ICV-STZ AD model mice compared with ICV-saline mice. Conclusion: All these data showed that FPR2 deficiency could improve learning and attenuate tau hyperphosphorylation for ICV-STZ AD model mice, suggesting that FPR2 may play an important role in AD progression.
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