Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients

• Published in: Neurobiology of disease Vol. 106; pp. 269 - 278
• Main Authors: Rydbirk, Rasmus, Elfving, Betina, Andersen, Mille Dahl, Langbøl, Mia Aggergaard, Folke, Jonas, Winge, Kristian, Pakkenberg, Bente, Brudek, Tomasz, Aznar, Susana
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2017; Elsevier
• Subjects: Aged; CD45 reactivity; Cohort Studies; Cytokines - metabolism; Female; Glycogen synthase kinase 3 beta; Granulocyte colony-stimulating factor; Humans; Immunohistochemistry; Inflammation - metabolism; Inflammation - pathology; Interleukin-13; Interleukin-2; Major histocompatibility complex class II; Male; Multiple System Atrophy; Multiple System Atrophy - immunology; Multiple System Atrophy - pathology; Neuroinflammation; Neurons - immunology; Neurons - pathology; Parkinson Disease - immunology; Parkinson Disease - pathology; Parkinson's Disease; Prefrontal Cortex - immunology; Prefrontal Cortex - pathology; RNA, Messenger - metabolism; S100 calcium binding protein B; CD45 reactivity; Glycogen synthase kinase 3 beta; Interleukin-2; Granulocyte colony-stimulating factor; S100 calcium binding protein B; Major histocompatibility complex class II; Multiple System Atrophy; Interleukin-13; Neuroinflammation; Parkinson's Disease
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2017.07.014

Parkinson's Disease (PD) and Multiple System Atrophy (MSA) are neurodegenerative diseases characterized neuropathologically by alpha-synuclein accumulation in brain cells. This accumulation is hypothesized to contribute to constitutive neuroinflammation, and to participate in the neurodegeneration. Cytokines, which are the main inflammatory signalling molecules, have been identified in blood and cerebrospinal fluid of PD patients, but studies investigating the human brain levels are scarce. It is documented that neurotrophins, necessary for survival of brain cells and known to interact with cytokines, are altered in the basal ganglia of PD patients. In regards to MSA, no major study has investigated brain cytokine or neurotrophin protein expression. Here, we measured protein levels of 18 cytokines (IL-2, 4–8, 10, 12, 13, 17, G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1α and 1β, TNF-α) and 5 neurotrophins (BDNF, GDNF, bFGF, PDGF-BB, VEGF) in the dorsomedial prefrontal cortex in brains of MSA and PD patients and control subjects. We found altered expression of IL-2, IL-13, and G-CSF, but no differences in neurotrophin levels. Further, in MSA patients we identified increased mRNA levels of GSK3β that is involved in neuroinflammatory pathways. Lastly, we identified increased expression of the neurodegenerative marker S100B, but not CRP, in PD and MSA patients, indicating local rather than systemic inflammation. Supporting this, in both diseases we observed increased MHC class II+ and CD45+ positive cells, and low numbers of infiltrating CD3+ cells. In conclusion, we identified neuroinflammatory responses in PD and MSA which seems more widespread in the brain than neurotrophic changes. •IL-2 protein levels are increased in the prefrontal cortex of PD and MSA brains.•IL-13 and G-CSF protein levels are decreased in PD and MSA brains.•Neurons express IL-2 and G-CSF protein.•MHC class II and CD45 reactivity is increased in PD and MSA brains.•GSK3B and S100B mRNA levels are increased in MSA brains.