کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
5629165 1580140 2018 11 صفحه PDF سفارش دهید دانلود کنید
عنوان انگلیسی مقاله ISI
Research PaperReversible induction of TDP-43 granules in cortical neurons after traumatic injury
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موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
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Research PaperReversible induction of TDP-43 granules in cortical neurons after traumatic injury
چکیده انگلیسی


- Traumatic Cortical Injury triggers the formation of cytoplasmic phospho-TDP-43 granules.
- Granules induction is larger and more sustained in TDP-43 transgenic mice.
- Astrocyte and leukocyte response to injury is stronger in TDP-43 transgenic mice.
- pTDP-43 granules are not stress granules but colocalize with FMRP and p62.
- Cytoplasmic phosphor-TDP-43 granules are not stable and disappear in time.

Traumatic brain injury (TBI) has been proposed as a risk factor for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). To determine whether TBI might trigger or exacerbate ALS-relevant pathology, we delivered a mild stab-wound injury to the motor cortex of three different ALS mouse models expressing mutations in SOD1, TDP-43 or FUS and scrutinized the effects on the formation of phospho-TDP-43 (pTDP-43) cytoplasmic granules. Stab-injury induced the formation of cytoplasmic TDP-43 granules in wt animals, peaking at 3 dpi; a much larger response was seen in mutant TDP-43 mice, whose response peaked at 7 dpi. The pTDP-43 granules did not colocalize with the stress markers TIAR-1 and FUS but colocalized with FMRP (35%) and with p62 (65%), suggesting their involvement in transport granules and their clearance by autophagy. A similar, albeit smaller effect, was seen in mutant FUS mice. In the SOD1G93A mouse model, neither increase in pTDP-43 granules nor in SOD1 aggregates were detected. In all cases, pTDP-43 granules were cleared and the number of pTDP-43-positive neurons returned to baseline by 40 dpi. Neither injury-related neuronal loss nor motor performance or survival was significantly different in transgenic mice receiving injury vs sham mice. Thus, trauma can trigger ALS-related TDP-43 pathology, the extent of which is modulated by ALS-related mutations. However, the pathological findings prove reversible and do not affect disease progression and neuronal vulnerability.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 299, Part A, January 2018, Pages 15-25
نویسندگان
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