Fig. 8

Long-term CSF1R inhibition increases microglial soma size and extranigral major histocompatibility complex II expression. A–D Ionized calcium-binding adaptor molecule 1 (Iba1, green) and phosphorylated alpha-synuclein (pSyn, red) immunofluorescence in the ipsilateral substantia nigra pars compacta (SNpc) 6 months following intrastriatal alpha-synuclein preformed fibril (α-syn PFF) or phosphate buffered saline (PBS) injection, with or without Pexidartinib (PLX3397B). Modest accumulation of pSyn immunoreactive neurons in the ipsilateral SNpc is evident following α-syn PFF injection. E Quantification of microglial soma size demonstrates a significant increase associated with PLX3397B treatment. In rats not fed PLX3397B, α-syn PFF injection is associated with increased microglial soma size. F Major histocompatibility complex II immunoreactive (MHC-IIir) microglia in the ipsilateral SNpc of α-syn PFF and PBS injected rats, with and without 6 months of PLX3397B treatment. G Quantification of MHC-IIir microglia in the SNpc demonstrates a significant degeneration-associated increase as compared to PBS injected rats at 6 months that is not affected by PLX3397B treatment. H MHC-II expression outside of the SNpc in both α-syn PFF and PBS rats after 6 months PLX3397B treatment. I Quantification of MHC-IIir expression in the midbrain parenchyma revealed a significant increase associated with long term PLX3397B treatment. Values represent the mean ± SEM. Black outline = no PLX3397B, green outline = PLX3397B. ****p < 0.0001 ***p = 0.001, ** p < 0.01, *p < 0.05. Scale bars in A–D and F are 100 µm. scale bars in H are 500 µm