Effects of Exercise Training on the Phosphoproteomics of the Medial Prefrontal Cortex in Rats With Autism Spectrum Disorder Induced by Valproic Acid.

IF 3.7 2区医学 Q1 CLINICAL NEUROLOGY

Neurorehabilitation and Neural Repair Pub Date : 2023-02-01 DOI:10.1177/15459683231152814

Genghong Tu, Youli Guo, Ruoshi Xiao, Lianying Tang, Min Hu, Bagen Liao

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引用次数: 0

Abstract

Background: The key neural pathological characteristics of autism spectrum disorder (ASD) include abnormal synaptic plasticity of the medial prefrontal cortex (mPFC). Exercise therapy is widely used to rehabilitate children with ASD, but its neurobiological mechanism is unclear.

Methods: To clarify whether the structural and molecular plasticity of synapses in the mPFC are related to improvement in ASD behavioral deficits after continuous exercise rehabilitation training, we applied phosphoproteomic, behavioral, morphological, and molecular biological methods to investigate the impact of exercise on the phosphoprotein expression profile and synaptic structure of the mPFC in valproic acid (VPA)-induced ASD rats.

Results: Exercise training differentially regulated the density, morphology, and ultrastructure of synapses in mPFC subregions in the VPA-induced ASD rats. In total, 1031 phosphopeptides were upregulated and 782 phosphopeptides were downregulated in the mPFC in the ASD group. After exercise training, 323 phosphopeptides were upregulated, and 1098 phosphopeptides were downregulated in the ASDE group. Interestingly, 101 upregulated and 33 downregulated phosphoproteins in the ASD group were reversed after exercise training, and these phosphoproteins were mostly involved in synapses. Consistent with the phosphoproteomics data, the total and phosphorylated levels of the proteins MARK1 and MYH10 were upregulated in the ASD group and reversed after exercise training.

Conclusions: The differential structural plasticity of synapses in mPFC subregions may be the basic neural architecture of ASD behavioral abnormalities. The phosphoproteins involved in mPFC synapses, such as MARK1 and MYH10, may play important roles in the exercise rehabilitation effect on ASD-induced behavioral deficits and synaptic structural plasticity, which requires further investigation.

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运动训练对丙戊酸所致自闭症谱系障碍大鼠内侧前额叶皮层磷酸化蛋白质组学的影响。

背景:自闭症谱系障碍(ASD)的主要神经病理特征包括内侧前额叶皮层(mPFC)突触可塑性异常。运动疗法被广泛应用于自闭症儿童的康复，但其神经生物学机制尚不清楚。方法:为明确持续运动康复训练后，mPFC突触的结构和分子可塑性是否与ASD行为缺陷的改善有关，我们应用磷酸蛋白组学、行为学、形态学和分子生物学等方法，研究运动对丙戊酸(VPA)诱导的ASD大鼠mPFC磷酸化蛋白表达谱和突触结构的影响。结果:运动训练对vpa诱导的ASD大鼠mPFC亚区突触的密度、形态和超微结构有差异调节。总的来说，ASD组mPFC中有1031个磷酸化肽上调，782个磷酸化肽下调。运动训练后，ASDE组323个磷酸化肽上调，1098个磷酸化肽下调。有趣的是，运动训练后，ASD组中101个上调的磷酸化蛋白和33个下调的磷酸化蛋白被逆转，这些磷酸化蛋白主要参与突触。与磷酸化蛋白质组学数据一致，ASD组中MARK1和MYH10蛋白的总水平和磷酸化水平上调，运动训练后逆转。结论:mPFC亚区突触结构可塑性的差异可能是ASD行为异常的基本神经结构。参与mPFC突触的磷酸化蛋白，如MARK1和MYH10，可能在运动康复对asd诱导的行为缺陷和突触结构可塑性的影响中发挥重要作用，有待进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurorehabilitation and Neural Repair 医学-康复医学

CiteScore

8.30

自引率

4.80%

发文量

审稿时长

6-12 weeks

期刊介绍： Neurorehabilitation & Neural Repair (NNR) offers innovative and reliable reports relevant to functional recovery from neural injury and long term neurologic care. The journal''s unique focus is evidence-based basic and clinical practice and research. NNR deals with the management and fundamental mechanisms of functional recovery from conditions such as stroke, multiple sclerosis, Alzheimer''s disease, brain and spinal cord injuries, and peripheral nerve injuries.