Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson's disease. Academic Article uri icon

Overview

abstract

  • Microglial activation and oxidative stress are significant components of the pathology of Parkinson's disease (PD), but their exact contributions to disease pathogenesis are unclear. We have developed an in vitro model of nigral injury, in which lipopolysaccharide-induced microglial activation leads to injury of a dopaminergic cell line (MES 23.5 cells) and dopaminergic neurons in primary mesencephalic cell cultures. The microglia are also activated by PD IgGs in the presence of low-dose dopa-quinone- or H(2)O(2)-modified dopaminergic cell membranes but not cholinergic cell membranes. The activation requires the microglial FCgammaR receptor as demonstrated by the lack of activation with PD IgG Fab fragments or microglia from FCgammaR-/- mice. Although microglial activation results in the release of several cytokines and reactive oxygen species, only nitric oxide and H(2)O(2) appear to mediate the microglia-induced dopaminergic cell injury. These studies suggest a significant role for microglia in dopaminergic cell injury and provide a mechanism whereby immune/inflammatory reactions in PD could target oxidative injury relatively specifically to dopaminergic cells.

publication date

  • November 1, 2001

Research

keywords

  • Dopamine
  • Microglia
  • Neurons
  • Parkinson Disease

Identity

PubMed Central ID

  • PMC6762816

Scopus Document Identifier

  • 0035503074

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.21-21-08447.2001

PubMed ID

  • 11606633

Additional Document Info

volume

  • 21

issue

  • 21