Chemokines in the MPTP model of Parkinson's disease: Absence of CCL2 and its receptor CCR2 does not protect against striatal neurodegeneration

Yogeshwar V. Kalkonde, William W. Morgan, Jose Sigala, Shivani K. Maffi, Carlo Condello, William Kuziel, Seema S. Ahuja, Sunil K. Ahuja

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Recent studies have invoked inflammation as a major contributor to the pathogenesis of Parkinson's disease (PD). We determined the role of members of the chemokine system, key inflammatory mediators, in PD pathogenesis. In the MPTP model of murine PD, several chemokines, including CC chemokine ligand 2 (CCL2, Monocyte Chemoattractant Protein-1) and CCL3 (Macrophage Inflammatory Protein-1α), were upregulated in the striatum and the ventral midbrain. Astrocytes were the predominant source of CCL2 and CCL3 in the striatum and the substantia nigra, and dopaminergic neurons in the substantia nigra constitutively expressed these two chemokines. MPTP treatment resulted in decreased CCL2 expression and increased CCL3 expression in the surviving dopaminergic neurons. Because we found that CCL2 induced production of TNF-α in microglial cells, a cytokine known to play a detrimental role in PD, we anticipated that deletion of the genes encoding CCL2 and CCR2, its major receptor, would confer a protective phenotype. However, MPTP-induced striatal dopamine depletion was comparable in double knockout and wild-type mice. Our results demonstrate that chemokines such as CCL2 are induced following MPTP treatment, but that at least within the context of this PD model, the absence of CCL2 and CCR2 does not protect against striatal dopamine loss.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalBrain Research
Volume1128
Issue number1
DOIs
StatePublished - Jan 12 2007

Keywords

  • CCL2
  • CCR2
  • Chemokines
  • MPTP
  • Parkinson's disease
  • glia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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