Exosome-associated mitochondrial DNA in late-life depression: Implications for cognitive decline in older adults
Date
2024-06
Authors
Mendes-Silva, Ana Paula
Nikolova, Yuliya S.
Rajji, Tarek K.
Kennedy, James
Diniz, Breno
Gonçalves, Vanessa F.
Vieira, Erica
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Affective Disorders
ORCID
Type
Article
Degree Level
Abstract
Background: Disrupted cellular communication, inflammatory responses and mitochondrial dysfunction are consistently observed in late-life depression (LLD). Exosomes (EXs) mediate cellular communication by transporting molecules, including mitochondrial DNA (EX-mtDNA), playing critical role in immunoregulation alongside tumor necrosis factor (TNF). Changes in EX-mtDNA are indicators of impaired mitochondrial function and might increase vulnerability to adverse health outcomes. Our study examined EX-mtDNA levels and integrity, exploring their associations with levels of TNF receptors I and II (TNFRI and TNFRII), and clinical outcomes in LLD.
Methods: Ninety older adults (50 LLD and 40 controls (HC)) participated in the study. Blood was collected and exosomes were isolated using size-exclusion chromatography. DNA was extracted and EX-mtDNA levels and deletion were assessed using qPCR. Plasma TNFRI and TNFRII levels were quantified by multiplex immunoassay. Correlation analysis explored relationships between EX-mtDNA, clinical outcomes, and inflammatory markers.
Results: Although no differences were observed in EX-mtDNA levels between groups, elevated levels correlated with poorer cognitive performance (r = − 0.328, p = 0.002) and increased TNFRII levels (r = 0.367, p = 0.004). LLD exhibited higher deletion rates (F(83,1) = 4.402, p = 0.039), with a trend remaining after adjusting for covariates (p = 0.084). Deletion correlated with poorer cognitive performance (r = − 0.335, p = 0.002). No other associations were found.
Limitation: Cross-sectional study with a small number of participants from a specialized geriatric psychiatry treatment center.
Conclusion: Our findings suggest that EX-mtDNA holds promise as an indicator of cognitive outcomes in LLD. Additional research is needed to further comprehend the role of EX-mtDNA levels/integrity in LLD, paving the way for its clinical application in the future.
Description
Keywords
exosomes, mitochondrial DNA, late-life depression, cognitive function, inflammation
Citation
Mendes-Silva, A. P., Nikolova, Y. S., Rajji, T. K., Kennedy, J. L., Diniz, B. S., Gonçalves, V. F., & Vieira, E. L. (2024). Exosome-associated mitochondrial DNA in late-life depression: Implications for cognitive decline in older adults. Journal of Affective Disorders, 362, 217–224. https://doi.org/10.1016/j.jad.2024.06.092
Degree
Department
Program
Advisor
Committee
Part Of
item.page.relation.ispartofseries
DOI
https://doi.org/10.1016/j.jad.2024.06.092