کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
329445 1433628 2009 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Microglial responses to dopamine in a cell culture model of Parkinson's disease
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Microglial responses to dopamine in a cell culture model of Parkinson's disease
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 30, Issue 11, November 2009, Pages 1805–1817
نویسندگان
, , , , , , , ,