Experimental Study On Alzheimer-like Axonal Pathology In Rats With Lipopolysaccharide Induced Neuroinflammation

Objectives To investigate the expression of amyloidogenic proteins, especially the expression of BACE1in rat brain with LPS induced neuroinflammation, and explore the possible relationship between neuroinflammation and Alzheimer-like axonal pathology.Methods24normal adult male SD rats were used and randomly divided into experimental and control group. LPS or PBS was injected into the right lateral hippocampus by stereotaxis instrument. Animals survived for30days. Immunohistochemistry was used to detecte the expression of MHC-II in the rat brain with LPS-injected, and immuno-fluorescent double staining was used to observe the co-localization of MHC-Ⅱ/GFAP (astrocytes marker) and MHC-Ⅱ/CD11b (microglia marker); Then we examined the expression of BACE1in rat brain by western blot and immunohistochemistry; Using immunofluorescent double staining to observe the co-localization of BACE1/APP, BACE1/Aβ, BACEl/SYN (axonal marker) and BACE1/MAP2(dendritic marker).Results The expression of MHC-II was increased in the ipsilateral cortex and hippocampal after LPS injection, and the up-regulated MHC-Ⅱ mainly expressed in microglia, partly in astrocytes; The expression of BACE1was significantly elevated in the ipsilateral cortex and hippocampal in LPS-treated group, when compared with control group; The elevated BACE1was located in dystrophic axons, and colocalized with increased APP and Aβ.Conclusion LPS-induced neuroinflammatory caused the increased expression of BACE1in the ipsilateral hippocampus and cortex; The up-regulation of BACE1is associated with Alzheimer-like axonal pathology. Neuroinflammation could act as an initiative factor for Alzheimer-like axonal pathology in rat brain.