Fig. 10.

Effect of empty AAV9 vectors (AAV9-Ф) or AAV9 expressing human α-syn on the expression of markers of the microglial phenotype in rats not treated or treated with the AT1 antagonist candesartan (CAND) or telmisartan (TELM). AAV9 expressing human WT α-syn induced a significant increase in the expression of markers of the M1 cytotoxic phenotype (IL-1β, IL-6, iNOS, and TNF-α; a–d). The marked increase in TNF-α expression induced by AAV9 expressing human A53T α-syn is shown in (e). However, a decrease in the expression of the M2 repair/regenerative phenotype marker ARG-1 was observed (f). These changes were inhibited by simultaneous treatment with the AT1 blockers candesartan or telmisartan (a–f). The results were normalized to the values of the control group. For RT-PCR, the comparative cycle threshold values method (2^−ΔΔCt) was used. Gene expression was measured relative to that of the housekeeping transcripts (β-actin). The levels of TNF-α were quantified with rat specific enzyme-linked immunosorbent assay (ELISA) kits in picograms per milliliter protein and expressed as percentages of the content in the control group samples. Data are means ± SEM. ^*p < 0.05 relative to the AAV9-Ф-injected group; ^#p < 0.05 relative to the group injected with AAV9 expressing human α-syn. One-way ANOVA followed by Holm–Sidak post hoc test. Abbreviations: α-syn A53T = A53T mutated alpha-synuclein; α-syn WT, wild-type alpha-synuclein; ANOVA = analysis of variance; ARG-1 = arginase-1; CAND = candesartan; IL-1β = interleukin-1β; IL-6 = interleukin 6; iNOS = inducible nitric oxide synthase; TELM = telmisartan; TNF-α = tumor necrosis factor alpha; SEM = standard error of the mean; Ф = empty-null