Microglia proteome from the rat substantia nigra. Study in animal model of fluorocitrate-induced astrocyte dysfunction and microglia activation.

Nervous system inflammation and microglia activation are among hallmarks of Parkinson’s disease. Partial nigrostriatal neurodegeneration can be compensated. Interaction between neurons, microglia and astrocytes could be essential for this functional adaptation and neuronal survival in long-term, but which mechanisms are responsible is unknown. The aim was to check how astrocyte vs neuron degeneration affected differentially microglia activation proteome and which mechanisms were regulated. In a rat model of 7-day infusion by osmotic minipumps of fluorocitrate (FC) into the substantia nigra (SN) (doi: 10.1007/s12035-017-0529-z; doi: 10.1111/jnc.14605; doi: 10.1016/j.mito.2018.12.002) astrocytes become dysfunctional and die, strongly activating microglia in the process. 6-OHDA injected into medial forebrain bundle caused selective degeneration of dopaminergic neurons in the SN and only slightly activated microglia, probably via different mechanism. Controls were sham operated. Microglia cells were sorted out from dissociated SN tissue using FACS, and processed for mass spectrometry proteome analysis. Microglial response to dying astrocytes vs dying neurons was different. Understanding the role of individual cell type in the diseased tissue cellular context is essential to understand disease pathomechanisms and identify better pharmacological targets.