کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4351703 1298077 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Loss of glial fibrillary acidic protein marginally accelerates disease progression in a SOD1H46R transgenic mouse model of ALS
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Loss of glial fibrillary acidic protein marginally accelerates disease progression in a SOD1H46R transgenic mouse model of ALS
چکیده انگلیسی

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is highly expressed in reactive astrocytes. Increased production of GFAP is a hallmark of astrogliosis in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, the physiological and pathological roles of GFAP, particularly in chronic neurodegenerative conditions, remain unclear. To address this issue, we here investigate whether absence of GFAP affects the phenotypic expression of motor neuron disease (MND) using an H46R mutant Cu/Zn superoxide dismutase-expressing mouse model of ALS (SOD1H46R). GFAP deficient SOD1H46R mice showed a significant shorter lifespan than SOD1H46R littermates. Further, at the end stage of disease, loss of GFAP resulted in increased levels of Vim and Aif1 mRNAs, encoding vimentin and allograft inflammatory factor 1 (AIF1), respectively, in the spinal cord, although no discernible differences in the levels and distribution of these proteins between SOD1H46R and GFAP-deficient SOD1H46R mice were observed. These results suggest that loss of GFAP in SOD1H46R mice marginally accelerates the disease progression by moderately enhancing glial cell activation. Our findings in a mouse model of ALS may have implication that GFAP is not necessary for the initiation of disease, but it rather plays some modulatory roles in the progression of ALS/MND.


► Increased production of GFAP is a hallmark of astrogliosis in neurodegenerative diseases.
► Loss of GFAP shortened the survival of a mutant SOD1H46R transgenic mouse model of ALS.
► Loss of GFAP resulted in increased levels of Vim and Aif1 mRNAs in the spinal cord.
► GFAP plays some modulatory roles in the progression of ALS by regulating glial activation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Research - Volume 70, Issue 3, July 2011, Pages 321–329
نویسندگان
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