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Formyl Peptide Receptor 2 Deficiency Improves Cognition and Attenuates Tau Hyperphosphorylation and Astrogliosis in a Mouse Model of Alzheimer's Disease.
J Alzheimers Dis. 2019; 67(1):169-179.JA

Abstract

Alzheimer's disease (AD) is characterized by progressive loss of memory and other cognitive functions. Accumulation of amyloid-β (Aβ) and hyperphosphorylated tau are two major neuropathological features of AD. Formyl peptide receptor 2 (FPR2), contributing to innate immunity and inflammation, has been implicated in the uptake and clearance of Aβ. It remains unclear whether FPR2 affects cognition and tau phosphorylation. The effects of FPR2 in cognition and tau phosphorylation were examined using FPR2 knock-out (Fpr2-/-) mice receiving intracerebroventricular (ICV) injection of streptozotocin (STZ). The general behaviors and cognitive functions were evaluated using rotarod, open field test, and Morris water maze test. The alteration in tau hyperphosphorylation and activation of astrocytes were determined by using western blotting and/or immunofluorescence staining. ICV injection of STZ impaired spatial learning and memory of mice in Morris water maze. FPR2 deficiency improved spatial learning and memory of ICV-STZ mice. In the hippocampus and cortex of ICV-STZ mice, a marked increase was observed in tau phosphorylation at Ser199, Thr205, and Ser396 compared with ICV-saline control mice. However, FPR2 deficiency attenuated the hyperphosphorylation of tau at Ser199 and Ser396. In addition, the expression of GFAP was significantly increased in hippocampus and cortex of ICV-STZ mice. FPR2 deletion reduced the increase of GFAP expression induced by ICV injection of STZ. These results indicate that FPR2 deficiency is associate with improved cognition, reduced tau hyperphosphorylation, and activation of astrocytes in the mouse AD model tested. FPR2 may be a potential target in AD prevention and therapy.

Authors+Show Affiliations

School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China.School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China.School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China.School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China.School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China.School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China. Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30475772

Citation

Zhang, Haibo, et al. "Formyl Peptide Receptor 2 Deficiency Improves Cognition and Attenuates Tau Hyperphosphorylation and Astrogliosis in a Mouse Model of Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 67, no. 1, 2019, pp. 169-179.
Zhang H, Wang D, Gong P, et al. Formyl Peptide Receptor 2 Deficiency Improves Cognition and Attenuates Tau Hyperphosphorylation and Astrogliosis in a Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2019;67(1):169-179.
Zhang, H., Wang, D., Gong, P., Lin, A., Zhang, Y., Ye, R. D., & Yu, Y. (2019). Formyl Peptide Receptor 2 Deficiency Improves Cognition and Attenuates Tau Hyperphosphorylation and Astrogliosis in a Mouse Model of Alzheimer's Disease. Journal of Alzheimer's Disease : JAD, 67(1), 169-179. https://doi.org/10.3233/JAD-180823
Zhang H, et al. Formyl Peptide Receptor 2 Deficiency Improves Cognition and Attenuates Tau Hyperphosphorylation and Astrogliosis in a Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2019;67(1):169-179. PubMed PMID: 30475772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Formyl Peptide Receptor 2 Deficiency Improves Cognition and Attenuates Tau Hyperphosphorylation and Astrogliosis in a Mouse Model of Alzheimer's Disease. AU - Zhang,Haibo, AU - Wang,Ding, AU - Gong,Ping, AU - Lin,Aihua, AU - Zhang,Yan, AU - Ye,Richard D, AU - Yu,Yang, PY - 2018/11/27/pubmed PY - 2020/3/3/medline PY - 2018/11/27/entrez KW - Alzheimer’s disease KW - astrocyte activation KW - formyl peptide receptor 2 KW - tau phosphorylation SP - 169 EP - 179 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 67 IS - 1 N2 - Alzheimer's disease (AD) is characterized by progressive loss of memory and other cognitive functions. Accumulation of amyloid-β (Aβ) and hyperphosphorylated tau are two major neuropathological features of AD. Formyl peptide receptor 2 (FPR2), contributing to innate immunity and inflammation, has been implicated in the uptake and clearance of Aβ. It remains unclear whether FPR2 affects cognition and tau phosphorylation. The effects of FPR2 in cognition and tau phosphorylation were examined using FPR2 knock-out (Fpr2-/-) mice receiving intracerebroventricular (ICV) injection of streptozotocin (STZ). The general behaviors and cognitive functions were evaluated using rotarod, open field test, and Morris water maze test. The alteration in tau hyperphosphorylation and activation of astrocytes were determined by using western blotting and/or immunofluorescence staining. ICV injection of STZ impaired spatial learning and memory of mice in Morris water maze. FPR2 deficiency improved spatial learning and memory of ICV-STZ mice. In the hippocampus and cortex of ICV-STZ mice, a marked increase was observed in tau phosphorylation at Ser199, Thr205, and Ser396 compared with ICV-saline control mice. However, FPR2 deficiency attenuated the hyperphosphorylation of tau at Ser199 and Ser396. In addition, the expression of GFAP was significantly increased in hippocampus and cortex of ICV-STZ mice. FPR2 deletion reduced the increase of GFAP expression induced by ICV injection of STZ. These results indicate that FPR2 deficiency is associate with improved cognition, reduced tau hyperphosphorylation, and activation of astrocytes in the mouse AD model tested. FPR2 may be a potential target in AD prevention and therapy. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/30475772/Formyl_Peptide_Receptor_2_Deficiency_Improves_Cognition_and_Attenuates_Tau_Hyperphosphorylation_and_Astrogliosis_in_a_Mouse_Model_of_Alzheimer's_Disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-180823 DB - PRIME DP - Unbound Medicine ER -