Fig. 4.

Glial and neuronal proteins and pathways in EVs during EAE. a Heatmap of the relative neuron and glial cell contribution to the spinal cord EV pool before and 16 and 15 days after EAE induction. The deconvolution analysis was carried out using BRETIGEA. Graphs showing mean relative abundance of selected b oligodendrocyte lineage, c astrocyte, d microglial, e immature neuronal, and f mature neuronal markers in EVs at the different time points (± SD; n = 3 samples). g Heatmap showing the relative abundance of the top proteins (filtered for adjusted p-value < 0.01 and fold change kept at < − 1.5/> 1.5) from the “vesicle-mediated transport in synapse” GO term enriched in our data. Proteins are shown as gene symbols. h, i Pie charts showing the change of pre- vs postsynaptic protein and inhibitory vs excitatory synapse protein abundance. The cellular compartment gene ontology terms associated with the proteins detected were filtered: for pre- vs postsynaptic analysis to include either “presynaptic” and not “postsynaptic” (110 identified proteins) or “postsynaptic” but not “presynaptic” (295 identified proteins); and for inhibitory vs excitatory to include either both “GABA-ergic” and “inhibitory” (17 identified proteins) or both “glutamatergic” and “excitatory” (20 identified proteins). Numbers on the pie chart represent the percentage significantly up- (red) or downregulated (blue) proteins of all identified proteins of the particular synaptic compartment or type (significance defined by p < 0.05 and fold change > 1.2/< − 1.2)