Title:Tandem Mass Tag (TMT) Quantitative Proteomic Analysis of Serum
Exosomes in Cerebral Small-vessel Disease (CSVD) Patients With Depressive
Symptoms
Volume: 19
Issue: 5
Author(s): Yanjing Lu, Rong Shen, Hao Zhu, Qian Feng, Yifan Li, Wenxin Xu, Dayong Zhang, Zhong Zhao*Hua Zhou*
Affiliation:
- Department of Neurology,
The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215000, China
- Department of Neurology, Affiliated Hospital of Jiaxing University, Jiaxing, 314000 China
Keywords:
Proteomic, exosome, cerebral small-vessel disease, depression, estrogen, desmosomes, keratins.
Abstract:
Background: Depressive symptoms are one of the main clinical features of the cerebral
small-vessel disease (CSVD). However, the pathogenesis of depressive symptoms of CSVD has not
been fully studied, and a lack of effective diagnostic methodseffective diagnostic methods exists.
Recently, the emerging body of evidence regarding exosomes has rendered them potentially key
players in the neuropsychiatric disease theragnostic. This study’s aim was to investigate serumexosome
proteomic expression in CSVD patients with depressive symptoms and to screen and analyze
potential biomarkers for clinical diagnosis.
Methods: Serum samples were collected from 36 CSVD patients, including 18 cerebral small-vessel
disease (CSVD+D) patients with depressive clinical manifestations and 18 cerebral small-vessel
disease patients that did not present depression-related clinical manifestations (CSVD-D). This investigation
employed tandem mass tag (TMT) combined with mass spectrometry for sample detection
and quantitative analysis of proteins. The differential proteins with significant dysregulated
expression levels in patient plasma exosomes were screened and analyzed through bioinformatics
techniques.
Results: This investigation focused on a global collection of 659 quantifiable proteins. Compared to
the CSVD-D group, 7 up-regulated and 30 down-regulated proteins were identified in the CSVD+D
group (P < 0.05). Gene ontology (GO) enrichment analyses revealed proteomic expression profile
dysregulations within serum exosomes in patients with depression, such as desmosomes and
keratins, rendering them as potential biomarkers. Kyoto encyclopedia of genes and genomes
(KEGG) database investigations revealed the differentially expressed proteins to be highly aggregated
within the estrogen signaling pathway.
Conclusion: This investigation pioneered TMT proteomic evaluation of serum exosomes within
CSVD patients suffering from depression and reveals the shifts in proteomic expression profiles by
serum exosomes within such patients. This study identified several important molecular / signal
pathway abnormalities related to depression. These results provide a possible means to further clarify
the pathogenesis of depressive symptoms of cerebrovascular disease and its diagnosis and treatment
in the future.
