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

Nguyen, Vinh A., Carey, Leeanne M., Giummarra, Loretta, Faou, Pierre, Cooke, Ira, Howells, David W., Tse, Tamara, Macaulay, S. Lance, Ma, Henry, Davis, Stephen M., Donnan, Geoffrey A., and Crewther, Sheila G. (2016) 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. 85. pp. 1-16.

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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 ID: 44469
Item Type: Article (Research - C1)
ISSN: 1664-2295
Keywords: ischemic stroke, proteomics, post-stroke depression, complement and coagulation, immunity and inflammation, stroke neurological recovery, blood biomarkers
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© 2016 Nguyen, Carey, Giummarra, Faou, Cooke, Howells, Tse, Macaulay, Ma, Davis, Donnan and Crewther. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Funders: Commonwealth Scientific and Industrial Research Organization (CSIRO) , Preventative Health Flagship, James S. McDonnell Foundation, Victorian Government's Operational Infrastructure Support Program , Australian Research Council (ARC), La Trobe University
Projects and Grants: James S. McDonnell Foundation 21st Century Science Initiative in Cognitive Rehabilitation – Collaborative Award (# 220020413), ARC #FT0992299
Date Deposited: 23 Jun 2016 04:54
FoR Codes: 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310114 Systems biology @ 50%
31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310205 Proteomics and metabolomics @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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