@article{ref1,
title="Mechanical stretching-induced traumatic brain injury is mediated by the formation of GSK 3β-Tau-complex to impair insulin signaling transduction",
journal="Biomedicines",
year="2021",
author="Cheng, Pei-Wen and Wu, Yi-Chung and Wong, Tzyy-Yue and Sun, Gwo-Ching and Tseng, Ching-Jiunn",
volume="9",
number="11",
pages="e1650-e1650",
abstract="Traumatic brain injury confers a significant and growing public health burden. It is a major environmental risk factor for dementia. Nonetheless, the mechanism by which primary mechanical injury leads to neurodegeneration and an increased risk of dementia-related diseases is unclear. Thus, we aimed to investigate the effect of stretching on SH-SY5Y neuroblastoma cells that proliferate in vitro. These cells retain the dopamine-β-hydroxylase activity, thus being suitable for neuromechanistic studies. SH-SY5Y cells were cultured on stretchable membranes. The culture conditions contained two groups, namely non-stretched (control) and stretched. They were subjected to cyclic stretching (6 and 24 h) and 25% elongation at 1 Hz. Following stretching at 25% and 1 Hz for 6 h, the mechanical injury changed the mitochondrial membrane potential and triggered oxidative DNA damage at 24 h. Stretching decreased the level of brain-derived neurotrophic factors and increased amyloid-β, thus indicating neuronal stress. Moreover, the mechanical injury downregulated the insulin pathway and upregulated glycogen synthase kinase 3β (GSK-3β)(S9)/p-Tau protein levels, which caused a neuronal injury. Following 6 and 24 h of stretching, GSK-3β(S9) was directly bound to p-Tau(S396). In contrast, the neuronal injury was improved using GSK-3β inhibitor TWS119, which downregulated amyloid-β/p-Taus396 phosphorylation by enhancing ERK1/2T202/Y204 and AktS473 phosphorylation. Our findings imply that the neurons were under stress and that the inactivation of the GSK3β could alleviate this defect.<p /> <p>Language: en</p>",
language="en",
issn="2227-9059",
doi="10.3390/biomedicines9111650",
url="http://dx.doi.org/10.3390/biomedicines9111650"
}