CSF from Parkinson disease patients differentially affects cultured microglia and astrocytes.
BACKGROUND
Excessive and abnormal accumulation of alpha-synuclein (α-synuclein) is a factor contributing to pathogenic cell death in Parkinson's disease. The purpose of this study, based on earlier observations of Parkinson's disease cerebrospinal fluid (PD-CSF) initiated cell death, was to determine the effects of CSF from PD patients on the functionally different microglia and astrocyte glial cell lines. Microglia cells from human glioblastoma and astrocytes from fetal brain tissue were cultured, grown to confluence, treated with fixed concentrations of PD-CSF, non-PD disease control CSF, or control no-CSF medium, then photographed and fluorescently probed for α-synuclein content by deconvolution fluorescence microscopy. Outcome measures included manually counted cell growth patterns from day 1-8; α-synuclein density and distribution by antibody tagged 3D model stacked deconvoluted fluorescent imaging.


RESULTS
After PD-CSF treatment, microglia growth was reduced extensively, and a non-confluent pattern with morphological changes developed, that was not evident in disease control CSF and no-CSF treated cultures. Astrocyte growth rates were similarly reduced by exposure to PD-CSF, but morphological changes were not consistently noted. PD-CSF treated microglia showed a significant increase in α-synuclein content by day 4 compared to other treatments (p ≤ 0.02). In microglia only, α-synuclein aggregated and redistributed to peri-nuclear locations.


CONCLUSIONS
Cultured microglia and astrocytes are differentially affected by PD-CSF exposure compared to non-PD-CSF controls. PD-CSF dramatically impacts microglia cell growth, morphology, and α-synuclein deposition compared to astrocytes, supporting the hypothesis of cell specific susceptibility to PD-CSF toxicity.
Department of Neurology, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Mya C
MC
Schiess
Jennifer L
JL
Barnes
Timothy M
TM
Ellmore
Brian J
BJ
Poindexter
Kha
K
Dinh
Roger J
RJ
Bick
D001253:Astrocytes / Q000473:pathology* / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape / Q000502:physiology; D002478:Cells, Cultured; D002556:Cerebrospinal Fluid Proteins / Q000009:adverse effects*; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D017628:Microglia / Q000473:pathology* / Q000502:physiology; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000378:metabolism; D051844:alpha-Synuclein / Q000502:physiology
D002556:Cerebrospinal Fluid Proteins; D051844:alpha-Synuclein