کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2201273 1100008 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vivo 6-OHDA-induced neurodegeneration and nigral autophagic markers expression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
In vivo 6-OHDA-induced neurodegeneration and nigral autophagic markers expression
چکیده انگلیسی

Numerous reports suggest the involvement of oxidative stress in the pathogenesis of Parkinson's disease (PD), however, the crucial mechanism of the degenerative process remain unclear. Emerging evidence supports a critical role for autophagy in the pathogenic process of dopaminergic neurodegeneration. However, the definitive in vivo proof of it is currently lacking. Due to the relevance oxidative stress and chaperone-mediated autophagy (CMA) in PD pathogenesis, we investigated the expression of nigral CMA markers in 6-OHDA-lesioned hemiparkinsonian rats. Male Sprague–Dawley rats received a 6-OHDA injection (8 μg in 4 μl of saline with 0.02% ascorbate over 8 min) into the left medial forebrain bundle by means of a Harvard infusion pump. Following a three-week recovery period, rats exhibiting a vigorous rotational response (>100 total turns) to apomorphine (0.05 mg/kg, sc) were selected for further study. Western blotting analyses showed a decrease by 88% in TH expression levels in the striatum ipsilateral to 6-OHDA lesion (p < 0.01) associated to an increase in nigral lysosomal membrane protein receptor type 2A (LAMP2A, p < 0.01) and heat shock protein 90 (HSP90, p < 0.01). The present results provide in vivo evidence of CMA activation in the animal model of parkinsonism in rats with a unilateral lesion of the nigrostriatal pathway induced by 6-OHDA. This widely used model offers great potential for future studies regarding new potential treatments for neurodegenerative conditions and in the investigation of signaling pathways regulating autophagy.

Research highlights▶ 6-OHDA-induced lesion induces an increase in nigral lysosomal membrane protein receptor type 2A. ▶ 6-OHDA-induced lesion induces an increase in nigral heat shock protein 90 (HSP90). ▶ 6-OHDA induces CMA activation in vivo.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 58, Issue 4, March 2011, Pages 521–526
نویسندگان
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