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

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• 作者：Ana M. Espinosa-Oliva^a ; ^b ; ² ; Rocí ; o M. de Pablos^a ; ^b ; ² ; Manuel Sarmiento^a ; ^b ; ¹ ; Ruth F. Villará ; n^a ; ^b ; Alejandro Carrillo-Jimé ; nez^a ; ^b ; Marti Santiago^a ; ^b ; José ; L. Venero^a ; ^b ; Antonio J. Herrera^a ; ^b ; Josefina Cano^a ; ^b ; ³ ; Alberto Machado^a ; ^b ; ^{machado@us.es" class="auth_mail}
• 关键词：Dopaminergic brain structures ; Inflammation ; Macrophages ; Monocytes infiltration ; Neurodegeneration
• 刊名：Neurotoxicology
• 出版年：March, 2014
• 年：2014
• 卷：41
• 期：Complete
• 页码：89-101
• 全文大小：5643 K

文摘

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 (伪-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.