کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5814320 1556625 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Chronic cannabinoid receptor stimulation selectively prevents motor impairments in a mouse model of Huntington's disease
ترجمه فارسی عنوان
تحریک گیرنده های کانابینوئید مزمن به طور انتخابی از اختلالات حرکتی در یک مدل موش هانتینگتون جلوگیری می کند
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
چکیده انگلیسی


- Acute cannabinoid treatment does not ameliorate behavioral deficits in the R6/1 mouse model for HD.
- Chronic cannabinoid receptor stimulation prevents motor, but not social and cognitive impairments in R6/1 mice.
- Chronic treatment exerts neuroprotective effects in R6/1 animals.

Huntington's disease (HD) is a devastating neurodegenerative disease characterized by a progressive decline in motor abilities, as well as in cognitive and social behaviors. Most of these behavioral deficits are recapitulated in the R6/1 transgenic mouse, which can therefore be used as an experimental model to identify the neurobiological substrates of HD pathology and to design novel therapeutic approaches. The endocannabinoid system (ECS) is a relevant candidate to participate in the etiopathology of HD as it is a key modulator of brain function, especially in areas primarily affected by HD dysfunction such as the striatum. Thus, some studies have demonstrated an association between HD progression and alterations in the expression of several ECS elements, thereby suggesting that improving ECS function may constitute a useful strategy to eliminate or at least delay the appearance of HD symptoms. Here this hypothesis was specifically tested by evaluating whether the administration of a well-characterized cannabinoid receptor agonist (WIN 55,212), either acutely or chronically, improves the HD-like symptoms in R6/1 mice. While acute treatment did not change the behavioral phenotype of transgenic animals, chronic administration was able to prevent the appearance of motor deficits, to increase the number of striatal huntingtin inclusions and to prevent the loss of striatal medium-sized spiny neurons, without affecting the social or cognitive alterations. These findings suggest that prolonged administration of cannabinoid receptor agonists could be an appropriate strategy for selectively improving motor symptoms and stimulating neuroprotective processes in HD patients.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 89, February 2015, Pages 368-374
نویسندگان
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