Microglial responses to dopamine in a cell culture model of Parkinson's disease

Diego Mastroeni, Andrew Grover, Brian Leonard, Jeffrey N. Joyce, Paul D. Coleman, Brooke Kozik, Denise L. Bellinger, Joseph Rogers

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Activated microglia appear to selectively attack dopamine (DA) neurons in the Parkinson's disease (PD) substantia nigra. We investigated potential mechanisms using culture models. As targets, human SH-SY5Y cells were left undifferentiated (UNDIFF) or were differentiated with retinoic acid (RA) or RA plus brain-derived neurotrophic factor (RA/BDNF). RA/BDNF-treated cells were immunoreactive for tyrosine hydroxylase and the DA transporter, took up exogenous DA, and released DA after K+ stimulation. Undifferentiated and RA-treated cells lacked these characteristics of a DA phenotype. Co-culture of target cells with human elderly microglia resulted in elevated toxicity in DA phenotype (RA/BDNF) cells. Lipopolysaccharide (LPS) plus K+-stimulated DA release enhanced toxicity by 500-fold. DA induced microglial chemotaxis in Boyden chambers. Spiperone inhibited this effect. Cultured human elderly microglia expressed mRNAs for D1-D4 but not D5 DA receptors. The microglia, as well as PD microglia in situ, were also immunoreactive for D1-D4 but not D5 DA receptors. These findings demonstrate that activated microglia express DA receptors, and suggest that this mechanism may play a role in the selective vulnerability of DA neurons in PD.

Original languageEnglish (US)
Pages (from-to)1805-1817
Number of pages13
JournalNeurobiology of Aging
Volume30
Issue number11
DOIs
StatePublished - Nov 1 2009
Externally publishedYes

Keywords

  • Chemotaxis
  • Dopamine
  • Dopamine receptor
  • Microglia
  • Parkinson's disease
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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