Tau protein function: The mechanical exploration of axonal transport disorder caused by persistent pressure in dorsal root ganglia.

Lei Zhang,Li Tang,Xin‐Hua Cheng,Jun Fu

doi:10.1002/mgg3.580

Abstract

ObjectiveWe analyzed the function of Tau protein to explore the underlying mechanism of axonal transport disorder caused by persistent pressure in the dorsal root ganglia (DRG).MethodsWistar rats were divided into the sham operated group, the control group and the experimental group. The Wistar rat model of continuous compression of DRG was used for further investigation. DRG neurons were extracted and cultured, and the protein content was detected using bicinchoninic acid method. Western blotting and immunofluorescence assays were performed to detect the protein content. Intraperitoneal injection of lithium chloride was performed for interaction with Tau. The results were then analyzed statistically.ResultsAfter 2 weeks of sustained pressure, the expression level of Tau396 increased by 33%, while Tau404 increased by 25% in the DRG of the experimental group (p < 0.05). The expression level of PSD‐95 in the DRG decreased by 15% (p < 0.05), while the expression of vGluT1, vGluT3 and vAchT decreased significantly in the DRG of the experimental group (p < 0.05). There was no significant difference in the expression of vGluT2 and vGAT among the three groups (p > 0.05). After intervention with lithium chloride, the expression of phosphorylated Tau at the above sites decreased in varying degrees compared with the model group. The expression level of Tau404 was reduced by 55%, and that of Tau199 by 60% in the DRG of the experimental group.ConclusionChronic compression of DRG and hypoxia caused phosphorylation of Tau in axons and inhibition of PSD‐95, and the function of the synaptic glutamic acid vesicle is defective in the synapse. This process is crucial in the development and progression of axonal transport dysfunction induced by chronic DRG compression, and phosphorylation of Tau plays a substantial role in this process.

Highlights

Tau, a low molecular microtubule related protein, is concentrated in axons and dendrites, which are highly asymmetric phosphates
Compared with the normal control group and the sham operated group, Tau396 expression increased by 33% in the dorsal root ganglia (DRG) of the experimental group after 2 weeks of continuous compression while
Compared with the normal control group and the sham operated group, the expression level of Tau396 in the DRG increased by 33% after 2 weeks of continuous compression, while the expression level of Tau404 increased by 25% (p < 0.05) (Figure 1)

Summary

| INTRODUCTION

A low molecular microtubule related protein, is concentrated in axons and dendrites, which are highly asymmetric phosphates. Its misfolding (Tang et al, 2016) and molecular aggregation (Ahn et al, 2014) can weaken the function of its stable microtubules, resulting in the transport, storage and release of Tau (Frost, Gotz, & Feany, 2015), which leads to axonal transport disorder (Rodriguez‐Martin et al, 2016). Neuronal oxidative stress is an antecedent event of excessive phosphorylation of Tau, which leads to misfolding, high phosphorylation and abnormal aggregation of Tau, leading to axonal transport disorders. It has been reported that changes in the Tau phosphorylation can affect axon transport in the neurodegenerative disease model (Gao, Liu, Jiang, Ding, & Li, 2014; Wang, Wang, Li, Hao, & Wang, 2016). The purpose of this study was to investigate the underlying mechanism of axonal transport disorder in the spinal DRG of rats through the study of Tau function

| MATERIALS AND METHODS

| Methods

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Findings

| DISCUSSION