Research Paper Volume 11, Issue 18 pp 7978—7995
GSK-3β and ERK1/2 incongruously act in tau hyperphosphorylation in SPS-induced PTSD rats
- 1 Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 2 Cognitive Impairment Ward of Neurology Department, The Third Affiliated Hospital of Shenzhen University, Shenzhen 518001, Guangdong Province, China
- 3 Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan 430056, China
- 4 Co-innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China
received: August 11, 2019 ; accepted: September 15, 2019 ; published: September 23, 2019 ;https://doi.org/10.18632/aging.102303
How to Cite
Copyright © 2019 Wei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Post-traumatic stress disorder (PTSD) manifests in neurocognitive deficits in association with increased tau deposition, which mainly consist of phosphorylated tau in Alzheimer disease (AD) brain. However, the exact mechanism of PTSD inducing tau hyperphosphorylation remains unclear and therefore no effective treatment options are currently available. We here show that employing single prolonged stress (SPS), as a consensus PTSD model, induced a typical anxiety and abnormal hyperphosphorylation of tau at Ser202/Thr205 (AT8) and Ser404 but not at Ser199 and Ser396 in the hippocampus compared to the control rats. Furthermore, there was a decrease in the level of inactivated phosphorylated GSK-3β at Ser9, an increase in the level of activated phosphorylated GSK-3β at Thr216 and an obvious decrease in the level of activated phosphorylated ERK1/2, but no alterations in CaMKII and PP2A in hippocampus of SPS rats. On the other hand, the levels of both phosphorylated AKT and total SGK1, stress- and GSK-3β/ERK1/2-related proteins, were down-regulated. Interestingly, Overexpression of SGK1 increased the level of phosphorylated ERK1/2 and led to tau hyperphosphorylation at Ser199 and Ser396. These findings suggest that SPS exposure results in differential tau phosphorylation at different sites probably due to incongruous action between AKT-related GSK-3β activation and SGK1-related ERK1/2 inactivation, suggesting a link between SPS-induced PTSD and AD-associated tau pathogenic mechanisms.
PTSD: Post-traumatic stress disorder; SPS: Single prolonged stress; AD: Alzheimer’s disease; NFTs: Neurofibrillary tangles; PHFs: Paired helical filaments.