Plasma-based proteomics reveals lipid metabolic and immunoregulatory dysregulation in post-stroke depression.
BACKGROUND
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.


METHODS
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.


RESULTS
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes--apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG)--were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control>PSD>stroke subjects; haptoglobin, stroke>PSD>healthy control.


CONCLUSIONS
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
Y
Y
Zhan
Department of Neurology, The First Affiliated Hospital at Chongqing Medical University, 1, Yixue Road, Yuzhong District, Chongqing, 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
Y-T
YT
Yang
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
H-M
HM
You
Department of Neurology, The First Affiliated Hospital at Chongqing Medical University, 1, Yixue Road, Yuzhong District, Chongqing, 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
D
D
Cao
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
C-Y
CY
Liu
Department of Neurology, The First Affiliated Hospital at Chongqing Medical University, 1, Yixue Road, Yuzhong District, Chongqing, 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
C-J
CJ
Zhou
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
Z-Y
ZY
Wang
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
S-J
SJ
Bai
Department of Neurology, The First Affiliated Hospital at Chongqing Medical University, 1, Yixue Road, Yuzhong District, Chongqing, 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
J
J
Mu
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
B
B
Wu
Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing, China.
Q-L
QL
Zhan
Department of Neurology, The First Affiliated Hospital at Chongqing Medical University, 1, Yixue Road, Yuzhong District, Chongqing, 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China. Electronic address: xiepeng@cqmu.edu.cn.
P
P
Xie
D000368:Aged; D053304:Apolipoprotein C-II / Q000378:metabolism; D001054:Apolipoproteins A / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003866:Depressive Disorder / Q000209:etiology / Q000378:metabolism*; D005260:Female; D018260:Gelsolin / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D020521:Stroke / Q000150:complications* / Q000378:metabolism
D053304:Apolipoprotein C-II; D001054:Apolipoproteins A; D018260:Gelsolin; D006023:Glycoproteins; D006242:Haptoglobins; C015246:LRG1 protein, human; C022205:apolipoprotein A-IV; D002097:C-Reactive Protein
PSD; Plasma; Post-stroke depression; Proteomic; Stroke