کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4347467 1296842 2009 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterization of chronic glutamate-mediated motor neuron toxicity in organotypic spinal cord culture prepared from ALS model mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Characterization of chronic glutamate-mediated motor neuron toxicity in organotypic spinal cord culture prepared from ALS model mice
چکیده انگلیسی

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons. Although organotypic spinal slice cultures (OSCs) exposed to inhibitors of glutamate uptake have been used as a model of ALS for screening of potentially therapeutic drugs, little development of such drugs has been achieved. In the present study we attempted to establish OSCs from G93A SOD1 transgenic mice (G93A) and to characterize the specific cell death pathway in motoneurons using glial cell line-derived neurotrophic factor (GDNF) in these mice. In the presence of GDNF, the number of surviving neurons in the OSCs was dramatically increased in both G93A and control mice. Exposure to threo-hydroxyaspartate (THA), a glutamate transport inhibitor, for 14 days induced loss of motoneurons in OSCs in G93A and control mice. In OSCs cultured with GDNF, THA-induced motoneuronal death was significantly inhibited in G93A mice, whereas that in control mice was not significantly affected. Moreover, the cleaved form of caspase-12 was increased after THA in the OSCs in G93A but not in control mice, and the activation of caspase-12 was attenuated by OSCs cultured with GDNF. These results suggest that the pathway responsible for motoneuronal death induced by THA in OSCs in G93A mice involves not only in excitotoxicity but also other mechanisms, and that the caspase-12-dependent ER stress pathway plays a role in spinal neuronal death in G93A mice. Moreover, OSCs prepared from the G93A mouse model of ALS may provide a suitable in vitro drug screening model for ALS.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 454, Issue 2, 24 April 2009, Pages 165–169
نویسندگان
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