کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6256797 1612948 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research reportA partial lesion model of Parkinson's disease in mice - Characterization of a 6-OHDA-induced medial forebrain bundle lesion
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Research reportA partial lesion model of Parkinson's disease in mice - Characterization of a 6-OHDA-induced medial forebrain bundle lesion
چکیده انگلیسی


- We establish a 6-OHDA partial MFB lesion mouse model.
- We correlate the 6-OHDA dose and degree of nigrostriatal lesion with behavioural impairment.
- Based on a statistical prediction model, we suggest behavioural tests and provide cut-off values to select partially-lesioned mice.

The most frequently used animal models for Parkinson's disease (PD) utilize unilateral injection of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle (MFB), which results in total denervation of the dopaminergic nigrostriatal pathway. However, neuroprotective interventions in PD require models resembling earlier stages of PD, where some dopaminergic cells and fibres remain.The aim of the present study was therefore to establish a MFB partial lesion model in mice.We tested four different 6-OHDA doses, and our results show a dose-dependent loss of nigral dopaminergic cells and striatal fibres that correlated with behavioural impairment in several behavioural tests. Specifically, doses of 0.7 μg and 1 μg of 6-OHDA induced a partial denervation of the nigrostriatal pathway, associated with a mild but quantifiable behavioural impairment. We identified the amphetamine-induced rotation, stepping, corridor and cylinder test to be sensitive enough to select partial lesion animals. Based on our data, we proposed a range of cut-off values for these different behavioural tests to select partial lesion mice. Using a statistical prediction model we identified two behavioural tests (the stepping test and amphetamine-induced rotation test) that with a high sensitivity and specificity predict the extent of nigral dopaminergic cell loss and select mice with a partial nigrostriatal lesion prior to further interventions.This model can serve as an important tool to study neuroprotective therapies for PD in mouse models, especially when the treatment targets the substantia nigra and/or the striatum.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Behavioural Brain Research - Volume 284, 1 May 2015, Pages 196-206
نویسندگان
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