TY - JOUR
T1 - Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients
AU - Rydbirk, Rasmus
AU - Elfving, Betina
AU - Andersen, Mille Dahl
AU - Langbøl, Mia Aggergaard
AU - Folke, Jonas
AU - Winge, Kristian
AU - Pakkenberg, Bente
AU - Brudek, Tomasz
AU - Aznar, Susana
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.nbd.2017.07.014
DO - 10.1016/j.nbd.2017.07.014
M3 - Journal article
C2 - 28732710
SN - 0969-9961
VL - 106
SP - 269
EP - 278
JO - Neurobiology of Disease
JF - Neurobiology of Disease
ER -
