Role of dopamine in the recruitment of immune cells to the nigro-striatal dopaminergic structures

Neurotoxicology. 2014 Mar:41:89-101. doi: 10.1016/j.neuro.2014.01.006. Epub 2014 Jan 30.

Abstract

Research indicates that inflammation and microglial activation are involved in the initiation and progression of Parkinson's disease (PD). Neuroinflammation contributes to the infiltration of peripheral immune cells and blood-brain barrier (BBB) leakage, linking peripheral and central inflammatory events in the pathogenesis of PD. Dopamine (DA) likely plays a role in this process. In the present study, the dopaminergic toxin 6-hydroxydopamine (6-OHDA) was used to damage dopaminergic neurons. Injection of 6-OHDA within the nigrostriatal pathway produced loss of astrocytes, disruption of the BBB, microglia activation and a reduction in osteopontin (OPN) immunoreactivity. Depletion of DA content by alpha-methylparatyrosine (α-MPT, a tyrosine hydroxylase inhibitor) reduced the infiltration of peripheral macrophages as well as the 6-OHDA-induced increase in microglial cells. DA could therefore be relevant in sustaining inflammation and lymphocyte recruitment induced by 6-OHDA, supporting DA implication in the degeneration of dopaminergic neurons induced by inflammatory processes.

Keywords: Dopaminergic brain structures; Inflammation; Macrophages; Monocytes infiltration; Neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Cell Movement
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Inflammation / chemically induced
  • Inflammation / immunology*
  • Inflammation / pathology
  • Lymphocytes / drug effects
  • Lymphocytes / physiology*
  • Macrophages / drug effects
  • Macrophages / physiology*
  • Male
  • Motor Activity / drug effects
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Osteopontin / metabolism
  • Oxidopamine / pharmacology
  • Rats
  • Rats, Wistar
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism*
  • Sympatholytics / pharmacology
  • Time Factors
  • alpha-Methyltyrosine / pharmacology

Substances

  • Enzyme Inhibitors
  • Sympatholytics
  • Osteopontin
  • alpha-Methyltyrosine
  • Oxidopamine
  • Dopamine