GSK-3 β and ERK1/2 incongruously act in tau hyperphosphorylation in SPS-induced PTSD rats.

GSK-3β and ERK1/2 incongruously act in tau hyperphosphorylation in SPS-induced PTSD rats. Aging (Albany NY). 2019 Sep 23;11: Authors: Wei Z, Mahaman YAR, Zhu F, Wu M, Xia Y, Zeng K, Yang Y, Liu R, Wang JZ, Shu X, Wang X Abstract 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 t...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research