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Original Investigation

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

ORCID Icon, , ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon show all
Pages 33-45 | Received 08 Oct 2020, Accepted 28 Dec 2020, Published online: 28 Apr 2021
 

Abstract

Objectives

Extracellular vesicles, including exosomes, cross the blood brain barrier with their contents intact and can be assayed peripherally. Circulating exosomes have been studied in other neurodegenerative disorders, but there is scarce data in schizophrenia. This study aimed to examine neuropathology-relevant protein biomarkers in circulating plasma-derived exosomes from patients with schizophrenia and age- and sex-matched healthy controls.

Methods

Nanoparticle tracking analysis was used to determine the size and concentration of exosomes. Exosomal membrane marker (CD9) and specific target cargo protein (glial fibrillary acid protein[GFAP], synaptophysin, and α-II-Spectrin) immunopositivity was examined using Western blot analyses with band intensity quantified. Methods were consistent with the ‘Minimal information for studies of extracellular vesicles 2018’ (MISEV2018) guidelines.

Results

Exosomal GFAP concentration was significantly higher and α-II-Spectrin expression significantly lower in plasma obtained from schizophrenia patients. No group differences were observed between in plasma exosomal concentration and size or in CD9, calnexin, or synaptophysin levels.

Conclusions

Our results demonstrate a differential pattern of exosomal protein expression in schizophrenia compared to matched healthy controls, consistent with the hypothesised astroglial pathology in this disorder. These results warrant further examination of circulating exosomes as vehicles of novel peripheral biomarkers of disease in schizophrenia and other neuropsychiatric disorders.

Acknowledgements

None.

Statement of interest

None to declare.

Additional information

Funding

This work was supported by unrestricted research funds (SNRGY), Department of Veteran’s Affairs (Mohini Ranganathan), Brain and Behavior Research Foundation (Suhas Ganesh) and St Joseph's Foundation. (T. Mohanakumar).

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