CX3CL1 improves neuronal function in mice with Alzheimer’s disease by inhibiting microglial pyroptosis

Abstract:

Objective To investigate the effect of exogenous injection of chemokine C-X3-C-motif ligand 1（CX3CL1） on neuronal function in mice with Alzheimer’s disease（AD） and its mechanism.Methods APP/PS1 double transgenic mice were used to establish a model of AD，and the mice were randomly divided into control group，AD model group，AD+PBS group，and AD+CX3CL1 group. The mice in the AD+CX3CL1 group were given intracranial administration of CX3CL1，and those in the AD+PBS group were injected with an equal volume of PBS solvent. The open field test and the Morris water maze test were used to assess the cognitive behavior of mice，and immunofluorescent staining，TUNEL staining，Nissl staining，Western blotting，and RT-PCR were used to analyze hippocampal tissue.Results The AD mice receiving CX3CL1 injection showed an increase in movement distance，but without a significant difference（P=0.189）；however，in the water maze test，the AD+CX3CL1 group showed a significant reduction in the movement distance to reach the submerged platform（P=0.001）. The AD model group had significant increases in the expression levels of gasdermin D and inflammation-related proteins（P<0.05），while CX3CL1 injection significantly reduced the expression levels of these proteins（P<0.05）. The AD model group had significant reductions in the number of Nissl bodies and the expression levels of （synaptosomal-associated protein of 25 kDa（SNAP25），post synaptic density protein 95（PSD95），and vesicle-associated membrane protein 1（VAMP1），while the CX3CL1 group showed significant increases in the number of Nissl bodies（P=0.001） and the expression levels of SNAP25，PSD95，and VAMP1（P=0.043，0.026，and 0.003）.Conclusion Exogenous CX3CL1 injection can improve neuronal function and protect neurons from damage in AD mice by regulating inflammatory factors and reducing pyroptosis.