|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|5629165||1580140||2018||11 صفحه PDF||سفارش دهید||دانلود کنید|
- 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 3Â dpi; a much larger response was seen in mutant TDP-43 mice, whose response peaked at 7Â 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 40Â 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.
Journal: Experimental Neurology - Volume 299, Part A, January 2018, Pages 15-25