کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2201273 | 1100008 | 2011 | 6 صفحه PDF | دانلود رایگان |

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.
Journal: Neurochemistry International - Volume 58, Issue 4, March 2011, Pages 521–526