title: In vivo 6-OHDA-induced neurodegeneration and nigral autophagic markers expression.
abstract: 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.
authors.affiliation: Laboratori de Neurologia Experimental, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. cmarin@clinic.ub.es
authors.forename: C
authors.initials: C
authors.lastname: Marin
authors.forename: E
authors.initials: E
authors.lastname: Aguilar
mesh_terms: D000818:Animals; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D008297:Male; D018384:Oxidative Stress; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D016627:Oxidopamine