Formyl Peptide Receptor 2 Deficiency Improves Cognition and Attenuates Tau Hyperphosphorylation and Astrogliosis in a Mouse Model of Alzheimer's Disease.

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: Haibo Zhang, Ding Wang, Ping Gong, Aihua Lin, Yan Zhang, Richard D Ye, Yang Yu
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 67 Issue 1 Pg. 169-179 ( 2019) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 30475772 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Formyl Peptide
• formyl peptide receptor 2, mouse
• tau Proteins
• Streptozocin

Topics

• Alzheimer Disease (chemically induced, genetics, pathology)
• Animals
• Astrocytes (pathology)
• Behavior, Animal (drug effects)
• Cognition (physiology)
• Disease Models, Animal
• Gliosis (genetics, pathology)
• Injections, Intraventricular
• Maze Learning (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phosphorylation
• Psychomotor Performance (drug effects)
• Receptors, Formyl Peptide (deficiency, genetics)
• Streptozocin (toxicity)
• tau Proteins (metabolism)