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A pathway proteomic profile of ischemic stroke survivors reveals innate immune dysfunction in association with mild symptoms of depression - a pilot study


Nguyen, VA and Carey, LM and Giummarra, L and Faou, P and Cooke, I and Howells, DW and Tse, T and Macaulay, SL and Ma, H and Davis, SM and Donnan, GA and Crewther, SG, A pathway proteomic profile of ischemic stroke survivors reveals innate immune dysfunction in association with mild symptoms of depression - a pilot study, Frontiers in Neurology, 7 Article 85. ISSN 1664-2295 (2016) [Refereed Article]


Copyright Statement

Copyright 2016 The Author(s) Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.3389/fneur.2016.00085


Depression after stroke is a common occurrence, raising questions as to whether depression could be a long-term biological and immunological sequela of stroke. Early explanations for post-stroke depression (PSD) focused on the neuropsychological/psychosocial effects of stroke on mobility and quality of life. However, recent investigations have revealed imbalances of inflammatory cytokine levels in association with PSD, though to date, there is only one published proteomic pathway analysis testing this hypothesis. Thus, we examined the serum proteome of stroke patients (n = 44, mean age = 63.62 years) and correlated these with the Montgomery-Åsberg Depression Rating Scale (MADRS) scores at 3 months post-stroke. Overall, the patients presented with mild depression symptoms on the MADRS, M = 6.40 (SD = 7.42). A discovery approach utilizing label-free relative quantification was employed utilizing an LC-ESI-MS/MS coupled to a LTQ-Orbitrap Elite (Thermo-Scientific). Identified peptides were analyzed using the gene set enrichment approach on several different genomic databases that all indicated significant downregulation of the complement and coagulation systems with increasing MADRS scores. Complement and coagulation systems are traditionally thought to play a key role in the innate immune system and are established precursors to the adaptive immune system through pro-inflammatory cytokine signaling. Both systems are known to be globally affected after ischemic or hemorrhagic stroke. Thus, our results suggest that lowered complement expression in the periphery in conjunction with depressive symptoms post-stroke may be a biomarker for incomplete recovery of brain metabolic needs, homeostasis, and inflammation following ischemic stroke damage. Further proteomic investigations are now required to construct the temporal profile, leading from acute lesion damage to manifestation of depressive symptoms. Overall, the findings provide support for the involvement of inflammatory and immune mechanisms in PSD symptoms and further demonstrate the value and feasibility of the proteomic approach in stroke research.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Howells, DW (Professor David Howells)
ID Code:117205
Year Published:2016
Web of Science® Times Cited:19
Deposited By:Medicine
Deposited On:2017-06-02
Last Modified:2017-11-06
Downloads:112 View Download Statistics

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