Potentially neurotoxic systems involved in traumatic and degenerative diseases of the brain were assessed in acute
psychosis. Astrocyte-derived exosomes (ADEs) and neuron-derived exosomes (NDEs) were immunoprecipitated from plasma of ten untreated first-episode psychotics (FPs) and ten matched normal controls (Cs). Neural mitochondrial electron transport and
complement proteins were extracted, quantified by ELISAs and normalized with levels of CD81 exosome marker. Levels of subunits 1 and 6 of
NADH-ubiquinone oxidoreductase (complex I) and subunit 10 of
cytochrome b-c1
oxidase (
complex III), but not of subunit 1 of
cytochrome C oxidase (complex IV) or
superoxide dismutase 1 (SOD1) were significantly lower in ADEs and NDEs of FPs than Cs. This dysregulated pattern of electron transport
proteins is associated with increased generation of
reactive oxygen species. ADE
glial fibrillary acidic protein levels were significantly higher in FPs than Cs, indicating a higher percentage of inflammatory astrocytes in FPs. ADE levels of C3b
opsonin were significantly higher and those of
C5b-9 attack complex was marginally higher in FPs than Cs. A significantly lower ADE level of the
C3 convertase inhibitor CD55 may explain the higher levels of
C3 convertase-generated C3b. ADE levels of the neuroprotective
protein leukemia inhibitory factor (LIF) were significantly lower in FPs than Cs, whereas levels of
IL-6 were no different. Plasma neural exosome levels of electron transport and
complement proteins may be useful in predicting FP and guiding
therapy. SOD mimetics,
C3 convertase inhibitors and LIF receptor agonists also may have therapeutic benefits in FP.