title: A Pathway Proteomic Profile of Ischemic Stroke Survivors Reveals Innate Immune Dysfunction in Association with Mild Symptoms of Depression - A Pilot Study.
abstract: 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.
authors.affiliation: Occupational Therapy, College of Science Health and Engineering, School of Allied Health, La Trobe University, Melbourne, VIC, Australia; Neurorehabilitation and Recovery, Stroke, The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia.
authors.forename: Vinh A
authors.initials: VA
authors.lastname: Nguyen
authors.affiliation: Occupational Therapy, College of Science Health and Engineering, School of Allied Health, La Trobe University, Melbourne, VIC, Australia; Neurorehabilitation and Recovery, Stroke, The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
authors.forename: Leeanne M
authors.initials: LM
authors.lastname: Carey
authors.affiliation: School of Psychology and Public Health, La Trobe University , Melbourne, VIC , Australia.
authors.forename: Loretta
authors.initials: L
authors.lastname: Giummarra
authors.affiliation: School of Molecular Sciences, La Trobe University , Melbourne, VIC , Australia.
authors.forename: Pierre
authors.initials: P
authors.lastname: Faou
authors.affiliation: School of Molecular Sciences, La Trobe University , Melbourne, VIC , Australia.
authors.forename: Ira
authors.initials: I
authors.lastname: Cooke
authors.affiliation: School of Medicine, University of Tasmania , Hobart, TAS , Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Howells
authors.affiliation: Occupational Therapy, College of Science Health and Engineering, School of Allied Health, La Trobe University, Melbourne, VIC, Australia; Neurorehabilitation and Recovery, Stroke, The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Tse
authors.affiliation: Commonwealth Science and Industrial Research Organisation (CSIRO) , Melbourne, VIC , Australia.
authors.forename: S Lance
authors.initials: SL
authors.lastname: Macaulay
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; Monash University, Clayton, VIC, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Ma
authors.affiliation: The University of Melbourne, Parkville, VIC, Australia; Department of Medicine, Melbourne Brain Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.affiliation: Neurorehabilitation and Recovery, Stroke, The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia.
authors.forename: Sheila G
authors.initials: SG
authors.lastname: Crewther
keywords: blood biomarkers; complement and coagulation; immunity and inflammation; ischemic stroke; post-stroke depression; proteomics; stroke neurological recovery