Reversible induction of TDP-43 granules in cortical neurons after traumatic injury.

Reversible induction of TDP-43 granules in cortical neurons after traumatic injury.
Exp Neurol. 2017 Sep 20;:
Authors: Wiesner D, Tar L, Linkus B, Chandrasekar A, Heuvel FO, Dupuis L, Tsao W, Wong PC, Ludolph A, Roselli F
Abstract
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 3dpi; a much larger response was seen in mutant TDP-43 mice, whose response peaked at 7dpi. 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 SOD1(G93A) 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 40dpi. Neither injury-related neuronal loss nor motor performance or survival was significantl...

Source: Experimental Neurology - September 20, 2017 Category: Neurology Authors: Wiesner D, Tar L, Linkus B, Chandrasekar A, Heuvel FO, Dupuis L, Tsao W, Wong PC, Ludolph A, Roselli F Tags: Exp Neurol Source Type: research