Fig. 7

Blockade of NMDA receptors rescues neurotoxicity caused by α-synuclein (auto)antibodies. (A) Representative images of neuronal NmC expression in α-syn + NmC overexpressing cultures before (pre-treatment, upper panel) and after 1 d (lower panel) of treatment with serum containing α-syn AAbs in the presence or absence of NMDA-R blockers, AP5 and memantine, or with antagonists of intracellular calcium transporters RyR (dantrolene) and IP3-R (2-APB). (B) Quantification of percent NmC-positive cells (relative to untreated cells) in α-syn + NmC overexpressing neurons at 1 d or 3 d post-treatment with serum containing α-syn AAb, in presence of blockers of calcium channels. (C) Quantification of percent NmC-positive cells /relative to untreated cells) in α-syn + NmC overexpressing neurons at 1 d or 3 d post-treatment with anti-α-syn Ab (138501), in presence of blockers of calcium channels. (D, E) Blocking other glutamate receptors like AMPA receptor with NBQX (D) or a complete blockade of neuronal activity using tetrodotoxin (TTX) (E) does not rescue α-syn Ab-mediated neurodegeneration. N = 3–5 biological and 6–10 technical replicates. Statistics by one-way ANOVA with Tukey’s (B) or Dunnett’s (C - E) multiple comparison test; statistical power (1-ß error probability) > 0.9 for all conditions. * = p < 0.05; ** = p < 0.01; *** = p < 0.001