Fig. 2. Intramuscular transmission of MSA prions.
TgM83+/− mice received intramuscular injection of 1% brain homogenate from one control and four MSA patient samples. (a, b) Kaplan–Meier plots show the onset of neurological signs following right thigh (a) and tongue (b) inoculation. Upticks indicate mice that did not die from synucleinopathy. (c, d) Frozen half-brains from all mice were tested in the α-syn140*A53T–YFP cell assay (× 103 A.U.). Closed circles indicate mice containing prions (above dotted line), while triangles indicate mice that died from other causes. Open circles indicate mice terminated at 450 dpi. (c) Mice inoculated into the thigh with MSA6 (P < 0.0001), MSA12 (P < 0.01), and MSA13 (P < 0.001) and (d) into the tongue with MSA6 (P < 0.01) contained significantly more α-synuclein prions than C2-inoculated mice. (e, f) Quantification of phosphorylated α-synuclein immunostaining in the HC, Thal, HTH, Mid, and pons of inoculated mice. MSA inoculation into the thigh (e) and tongue (f) induced α-synuclein pathology, but C2 inoculation had no effect. Data shown as mean ± standard deviation. (g, h) Detergent-insoluble phosphorylated α-synuclein was detected in the brains of mice inoculated with MSA in the thigh (g) and the tongue (h) but was not detected in C2-inoculated animals. * = P < 0.05, ** = P < 0.01, *** = P < 0.001, **** = P < 0.0001.