Genetically enhancing the expression of chemokine domain of CX3CL1 fails to prevent tau pathology in mouse models of tauopathy

• DOI: 10.1186/s12974-018-1310-6
• Publication Date: 2018-09-25T09:17:23Z
• Authors: Shane M. Bemiller; Nicole M. Maphis; Shane V. Formica; Gina N. Wilson; Crystal M. Miller; Guixiang Xu; Olga N. Kokiko-Co...; Ki-Wook Kim; Steffen Jung; Judy L. Cannon; Samuel D. Crish; Astrid E. Cardona; Bruce T. Lamb; Kiran Bhaskar
• Keywords: CX3CR1; CX3CL1; Tauopathy

Fractalkine (CX3CL1) and its receptor (CX3CR1) play an important role in regulating microglial function. We have previously shown that Cx3cr1 deficiency exacerbated tau pathology led to cognitive impairment. However, it is still unclear if the chemokine domain of ligand CX3CL1 essential neuronal pathology. used transgenic mice lacking endogenous Cx3cl1 (Cx3cl1−/−) expressing only obligatory soluble form (with domain) mucin stalk (referred as Cx3cl1105Δ mice) assess behavioral function both lipopolysaccharide (LPS) genetic (hTau) mouse models tauopathy. First, increased basal levels accompanied activation compared control groups. Second, CD45+ F4/80+ neuroinflammation phosphorylation were observed LPS, hTau/Cx3cl1−/−, hTau/Cx3cl1105Δ pathology, which correlated with impaired spatial learning. Finally, cell surface expression CX3CR1 was reduced mice, suggesting enhanced fractalkine internalization (mimicking deletion), likely contributes elevated Collectively, our data suggest overexpression does not protect against