Figure 2.

Intrinsic aberrant microglial activity and apoptotic spines can trigger synaptic stripping. ① HFD-induced hippocampal IL-1β elevation promotes the pro-inflammatory M1 phenotype in microglia. ② The aberrant microglia are attracted by CX3CL1 (Fractalkine) from the dendritic spine, which is recognized by the microglial CX3CR1. On the other hand, ③ reduced adiponectin level induces the accumulation of β-amyloid in the hippocampus. ④ Aβ accumulation causes mitochondrial dysfunction with the reduced mitochondrial membrane potential as well as the increased oxidative stress. The apoptotic mitochondrial releases cytochrome c which can activate flippase activity through caspase 3. ⑤ Phosphatidylserine located at the outer membrane of the phospholipid bilayer are served as an ‘eat-me’ signal, which is recognized by the receptors on the microglia. ⑥ Together, both aberrant microglial activity and malfunctioned neuronal mitochondria can trigger synaptic stripping by the microglia. Created with BioRender.com.