Oxidative Stress Signaling in Blast TBI-Induced Tau Phosphorylation

Date
2021-06-15
Authors
Wang, Chunyu
Shao, Changjuan
Zhang, Li
Siedlak, Sandra L.
Meabon, James S.
Peskind, Elaine R.
Lu, Yubing
Wang, Wenzhang
Perry, George
Cook, David G.
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Abstract

Traumatic brain injury caused by blast is associated with long-term neuropathological changes including tau phosphorylation and pathology. In this study, we aimed to determine changes in initial tau phosphorylation after exposure to a single mild blast and the potential contribution of oxidative stress response pathways. C57BL/6 mice were exposed to a single blast overpressure (BOP) generated by a compressed gas-driven shock tube that recapitulates battlefield-relevant openfield BOP, and cortical tissues were harvested at different time points up to 24 h after blast for Western blot analysis. We found that BOP caused elevated tau phosphorylation at Ser202/Thr205 detected by the AT8 antibody at 1 h post-blast followed by tau phosphorylation at additional sites (Ser262 and Ser396/Ser404 detected by PHF1 antibody) and conformational changes detected by Alz50 antibody. BOP also induced acute oxidative damage at 1 h post-blast and gradually declined overtime. Interestingly, Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were acutely activated in a similar temporal pattern as the rise and fall in oxidative stress after blast, with p38 showing a similar trend. However, glycogen synthase kinase-3 β (GSK3β) was inhibited at 1 h and remained inhibited for 24 h post blast. These results suggested that mitogenactivated protein kinases (MAPKs) but not GSK3β are likely involved in mediating the effects of oxidative stress on the initial increase of tau phosphorylation following a single mild blast.

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Keywords
blast, traumatic brain injury, tau phosphorylation, oxidative stress, ERK, JNK, p38, GSK3?
Citation
Antioxidants 10 (6): 955 (2021)
Department
Neuroscience, Developmental and Regenerative Biology
Chemistry