کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3069721 1580680 2012 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Involvement of microglial RhoA/Rho-Kinase pathway activation in the dopaminergic neuron death. Role of angiotensin via angiotensin type 1 receptors
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Involvement of microglial RhoA/Rho-Kinase pathway activation in the dopaminergic neuron death. Role of angiotensin via angiotensin type 1 receptors
چکیده انگلیسی

It has recently been shown that the dopaminergic cell loss induced by neurotoxins is enhanced by brain angiotensin II (AII) via type 1 receptors (AT1). However, the mechanisms involved in the dopaminergic degeneration and the brain inflammatory effects of AII have not been clarified. The RhoA–Rho-Kinase (ROCK) pathway may play a critical role in the inflammatory and oxidative effects of AII. In the substantia nigra of mice, administration of the dopaminergic neurotoxin MPTP induced an increase in the expression of RhoA and ROCK II mRNA levels and ROCK activity, which were inhibited by AT1 receptor deletion (i.e., in AT1a null mice treated with MPTP). Administration of the ROCK inhibitor Y-27632 or AT1 deletion induced a significant decrease in MPTP-induced microglial activation and dopaminergic cell death. In rat primary mesencephalic cultures treated with MPP+, the increase in dopaminergic cell loss induced by AII administration was also inhibited by treatment with Y27632. Intense expression of ROCK II was observed in the microglial cells in the substantia nigra of mice treated with MPTP, and the major role of the microglial ROCK was confirmed by comparing mesencephalic cultures with and without microglia. Activation of the RhoA/ROCK pathway is involved in the MPTP-induced dopaminergic degeneration, and in the enhancing effect of AII/AT1 activation on the microglial response and dopaminergic degeneration. ROCK inhibitors and AT1 receptor antagonists may provide new neuroprotective strategies against the progression of Parkinson's disease.


► RhoA/ROCK activation is involved in the MPTP-induced neuron death.
► ROCK activation mediates the enhancing effect of angiotensin on dopaminergic death.
► ROCK activation increases the MPTP-induced microglial response.
► MPP+ activates the RhoA/ROCK pathway in microglial cells.
► The RhoA–Rho-Kinase (ROCK) pathway is a major mediator of neuroinflammation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 47, Issue 2, August 2012, Pages 268–279
نویسندگان
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