Normally astrocytes promote CNS neuronal survival23. To determine whether A1s also promote neuronal survival, we co-cultured control and A1 reactive astrocytes with purified RGCs and measured viability. We found RGCs rapidly died when grown with increasing concentrations of A1 reactive astrocyte conditioned media (ACM, Fig. 4a,c). At the highest concentrations there was almost 100% death of cells (Fig. 4c). A1s were similarly toxic to cortical neurons, embryonic spinal motor neurons, and mature differentiated oligodendrocytes (Fig. 4b,d), however even at high doses spinal motor neurons remained around 20% viable; we found that preganglionic and gamma motor neurons were not susceptible to A1-induced toxicity (Extended Data Fig. 7m). Although not toxic to oligodendrocyte precursor cells, A1s were able to slow their differentiation and division (Extended Data Fig. 8). In addition, we tested susceptibility of human dopaminergic neurons to A1-induced toxicity and found that, like rodent cells, they also showed decreased viability with 25% of human dopaminergic cells dying due to A1-induced toxicity (Fig. 4e). This death could not be attributed to Il-1α, TNFα, and C1q alone, which did not cause death of
