4.4 Article

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

Journal

NEUROTOXICOLOGY
Volume 41, Issue -, Pages 89-101

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.neuro.2014.01.006

Keywords

Dopaminergic brain structures; Inflammation; Macrophages; Monocytes infiltration; Neurodegeneration

Funding

  1. Spanish Ministerio de Economia y Competitividad [SAF2012-39029]
  2. Junta de Andalucia Autonomous Government [CTS-6494 and CTS-5244]

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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 (alpha-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. (c) 2014 Elsevier Inc. All rights reserved.

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