Department of Sports Medicine, Guangzhou Sport University, Guangzhou, Guangdong, P.R. China.
Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Scientific Research Center, Guangzhou Sport University, Guangzhou, Guangdong, P.R. China.
Neurorehabil Neural Repair. 2023 Feb-Mar;37(2-3):94-108. doi: 10.1177/15459683231152814. Epub 2023 Mar 1.
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.
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.
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.
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.
自闭症谱系障碍（ASD）的关键神经病理学特征包括内侧前额叶皮质（mPFC）的异常突触可塑性。运动疗法广泛用于康复 ASD 儿童，但其神经生物学机制尚不清楚。
为了明确 mPFC 突触的结构和分子可塑性是否与连续运动康复训练后 ASD 行为缺陷的改善有关，我们应用磷酸化蛋白质组学、行为学、形态学和分子生物学方法，研究运动对 VPA 诱导的 ASD 大鼠 mPFC 中磷酸蛋白表达谱和突触结构的影响。
运动训练可调节 VPA 诱导的 ASD 大鼠 mPFC 亚区突触的密度、形态和超微结构。在 ASD 组中，mPFC 中共有 1031 个磷酸肽上调，782 个磷酸肽下调。运动训练后，ASDE 组中 323 个磷酸肽上调，1098 个磷酸肽下调。有趣的是，ASD 组中 101 个上调和 33 个下调的磷酸蛋白在运动训练后得到逆转，这些磷酸蛋白主要涉及突触。与磷酸蛋白质组学数据一致，ASD 组中 MARK1 和 MYH10 的总蛋白和磷酸化水平上调，并在运动训练后逆转。
mPFC 亚区突触的差异结构可塑性可能是 ASD 行为异常的基本神经结构。参与 mPFC 突触的磷酸蛋白，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作用中发挥重要作用，这需要进一步研究。
