The Role And Mechanism Of CSF1R In Myelin Degeneration

Microglia are immune cells in the brain and play an important role in maintaining normal brain function.It is a resident phagocyte in the central nervous system(CNS)and plays a protective role in nerve tissue injuries.Colony stimulating factor 1 receptor(CSF1R)is mainly expressed in microglia in the CNS.CSF1R(also named CD115)gene mutation leads to a disease named adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP).The pathological features of ALSP include extensive white matter degeneration,loss of myelin and axon,a large number of axon globular degeneration,and rich in lipid and pigment.However,the mechanism of myelin degeneration caused by abnormal Csf1r function is unclear.Here,we construct a chronic demyelination model by feeding dicyclohexanone oxalyldihydrazone(CPZ)in Csf1r heterozygous deletion mouse.We use immunohistochemical staining,immunofluorescence staining,Western blotting,real-time quantitative PCR,and electron microscopy to explore the role and molecular mechanism of CSF1R in neurodegenerative diseases.We found that heterozygous deletion of Csflr aggravated the demyelination and increased the transcription level of myelin basic protein induced by CPZ.Csf1r partial deletion did not affect the thickness of myelin sheath but reduced the proportion of myelinated nerve fibers in CPZ induced mouse model.Simultaneously,we observed that the number of microglia decreased and the number of astrocytes increased in CPZ-induced Csf1r heterozygous deletion mouse.These results indicate that CSF1R may open up a new way for the treatment of neurodegenerative diseases.