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Fig. 4 | Journal of Neuroinflammation

Fig. 4

From: Lewy body-like alpha-synuclein inclusions trigger reactive microgliosis prior to nigral degeneration

Fig. 4

Antigen-presenting MHC-II immunoreactive (MHC-IIir) microglia increase in the SNc in association with peak accumulation of α-syn inclusions but are limited during the interval of degeneration. ac Representative images of pSyn inclusions in the SNc at 2, 4, and 5 months p.i.; scale bar (ac) = 10 μm. d Stereological assessment of pS129 containing neurons in the substantia nigra in PFF animals at 1, 2, 3, 4, 5, and 6 months p.i.; *p ≤ 0.001 compared to 4, 5, and 6 months. #p ≤ 0.006 compared to 3, 4, 5, and 6 months. pSyn inclusions decrease over time in association with neuronal loss. e Major-histocompatibility complex-II (MHC-II; blue) protein colocalizes with ionized calcium-binding adaptor molecule 1 mRNA (brown) within microglia. f, g Representative images of MHC-II antigen-presenting microglia in the SN at 2 months in PBS- and PFF-injected rats and 6 months post-PFF injection (h); scale bar (fh) = 50 μm, insets = 10 μm. i Stereological assessment of MHC-IIir microglia in the SN reveals MHC-IIir microglia are significantly higher in PFF vs. PBS animals at 2, 4, and 5 months *p < 0.006. More MHC-IIir microglia are evident in 2-month PFF animals vs. all other PFF time points #p < 0.02. Notably, MHC-IIir microglia peak at the same time pSyn aggregation peaks (d, i). j Number of MHC-II immunoreactive microglia correlated with number of SNc neurons with intraneuronal pSyn inclusions (r = 0.8858, p = 0.0015, R2 = 0.7846). k In a follow-up study, intrastriatal injection of rat serum albumin (RSA) does not impact numbers of MHC-IIir microglia compared to PBS p > 0.05. Injection of PFFs in this second cohort confirmed previous observations of a significant increase in MHC-IIir microglia compared to PBS or RSA at 2 months p.i. *** p ≤ 0.0006. Abbreviations: p.i. = postinjection; PFFs = pre-formed alpha-synuclein fibrils; PBS = phosphate-buffered saline; RSA = rat serum albumin; MHC-II = major-histocompatibility complex-II; Iba-1 = ionized calcium binding adaptor molecule 1; ir = immunoreactive; SNc = substantia nigra pars compacta; SEM = standard error of the mean

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