Analysis of circulating exosomes reveals a peripheral signature of astrocytic pathology in schizophrenia

Abstract

Background: There is considerable interest in identifying peripheral biomarkers that reflect neuropathological changes in schizophrenia. Extracellular vesicles, including exosomes can cross the blood brain barrier with their contents intact and their cargo, including lipids, proteins and genetic materials can be assayed peripherally. Circulating exosomes have been studied in other neurodegenerative disorders, but there is scarce data in schizophrenia.Methods: We examined neuropathology relevant protein biomarkers in circulating exosomes from patients with schizophrenia and age and gender matched healthy controls using methods consistent with the recommended "Minimal information for studies of extracellular vesicles 2018" (MISEV2018) guidelines. Nanoparticle tracking analysis was used to determine the size and concentration of exosomes. Exosomal membrane marker (CD9) and specific target cargo proteins (glial fibrillary acid protein[GFAP], synaptophysin and α-II-spectrin) immunopositivity was examined using Western blot analyses and band intensity quantified.Results: No group differences were observed between schizophrenia and control samples in plasma exosomal concentration and size or in CD9 or calnexin positivity. Exosomal GFAP concentration was significantly higher and α-II-spectrin expression significantly lower in schizophrenia samples and there were no group differences observed for exosomal synaptophysin concentration. Conclusions: Our results demonstrate for the first time, a differential pattern of exosomal protein expression in schizophrenia compared to matched healthy controls, consistent with the hypothesized astro-glial pathology in this disorder. These results warrant further .

Modulation of Plasma Proteomic Profile by Regular Training in Male and Female Basketball Players: A Preliminary Study

“…It may also play a role in the extracellular release of microvesicles that differ from the exosomes ( Nabhan et al, 2012 ). Moreover, Spectrin, involved in secretion, is a ubiquitous cytoskeletal protein and its proteolysis leads in several cells to the biogenesis of plasma membrane EVs ( Ranganathan et al, 2021 ). The relationship between membrane and cytoskeleton provides structural stability and one of the proteins involved in this stability is Spectrin.…”

Exosomes in schizophrenia: Pathophysiological mechanisms, biomarkers, and therapeutic targets

“…Since exosomal proteins might play a role in SCZ, researchers examined neuropathology-relevant protein biomarkers, including synaptophysin which is a-II-Spectrin and Glial Fibrillary Acid Protein (GFAP), in the circulating plasma-derived exosomes of chronic SCZ and HCs [ 72 ]. The results depicted that the concentration of a-II-Spectrin was lower in SCZ while the exosomal samples from both groups had a similar concentration of synaptophysin, implying the presence of neuronally derived exosomes (NDE) irrespective of disease status.…”

Extracellular Vesicles in Mental Disorders: A State-of-art Review

“…25 perturbed metabolites in EVs related to metabolism of glycerophospholipid, phenylalanine, tyrosine, or tryptophan have been found to be linked to schizophrenia. [74] In detail, proteins or small molecules such as amyloid-beta 42 (Aβ42) [62] and glial fibrillary acidic protein was elevated, while α-II-spectrin [75], subunits 1 and 6 of NADHubiquinone oxidoreductase and subunit 10 of cytochrome b-c1 oxidase were lower in patients with schizophrenia, which provides evidence on the astrocyte-related neuroinflammatory underpinnings of the association between the dysregulated protein expression and increased reactive oxygen species. [76] Other research discovered dysregulation of miRNAs in EVs from postmortem brain tissues, CSF and peripheral blood in patients with schizophrenia or other mental disorders with psychosis.…”