Lee Chia-Ming, Nguyen Jennifer, Pope Brock, Imami Ali Sajid, Ryan V William George, Sahay Smita, Mathis Victoria, Pulvender Priyanka, Eby Hunter Michael, Arvay Taylen, Alganem Khaled, Wegman-Points Lauren, McCullunsmith Robert, Yuan Li-Lian
Department of Physiology and Pharmacology, College of Osteopathic Medicine, Des Moines University, Des Moines, Iowa, United States of America.
Department of Neurosciences and Psychiatry, College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio, United States of America.
PLoS One. 2025 Apr 15;20(4):e0321596. doi: 10.1371/journal.pone.0321596. eCollection 2025.
Regular exercise confers numerous physical and mental health benefits, yet individual variability in exercise participation and outcomes is still poorly understood. Uncovering the neurobiological mechanisms governing exercise behavior is essential for promoting physical activity and developing targeted interventions for related disorders. While genetic studies have provided insights, they often cannot account for protein-level alterations, such as changes in kinase activity. Here, we employ protein kinase activity profiling to delineate brain protein kinase activity and signaling networks modulated by acute voluntary exercise in rats. Focusing on the dorsal striatum, which governs voluntary exercise, as well as the hippocampus, which is susceptible to modulation by physical activity, we aim to understand the molecular basis of exercise behavior. Utilizing high throughput kinome array profiling and advanced pathway analyses, we identified protein kinase signaling pathways implicated in regulating voluntary exercise. Pathway analysis using Gene Ontology (GO) revealed significant alterations in 155 GO terms in the dorsal striatum and 206 GO terms in the hippocampus. Changes in kinase activity were observed in the striatum and hippocampus between the exercise (voluntary wheel running, VWR) and sedentary control rats. In both regions, global serine-threonine kinase (STK) activity was decreased, while global phospho-tyrosine kinase (PTK) activity was increased in VWR rats compared to control rats. We also identified specific kinases altered in VWR rats, including the IKappaB Kinase (IKK) and protein kinase delta (PKD) families. C-terminal src Kinase (CSK), epidermal growth factor (EGFR), and vascular endothelial growth factor receptor (VEGFR) tyrosine kinase were also enriched. These findings suggest regional heterogeneity of kinase activity following voluntary exercise, emphasizing potential molecular mechanisms underlying exercise behavior. This exploratory study lays the groundwork for future investigations into the causality of variations in exercise outcomes among individuals and different sexes, as well as the development of targeted interventions to promote physical activity and combat associated chronic diseases.
规律运动对身心健康有诸多益处，但人们对运动参与度和运动效果的个体差异仍知之甚少。揭示调控运动行为的神经生物学机制对于促进身体活动和开发针对相关疾病的靶向干预措施至关重要。虽然基因研究提供了一些见解，但它们往往无法解释蛋白质水平的变化，例如激酶活性的改变。在这里，我们采用蛋白激酶活性分析来描绘大鼠急性自愿运动所调节的脑蛋白激酶活性和信号网络。聚焦于控制自愿运动的背侧纹状体以及易受身体活动调节的海马体，我们旨在了解运动行为的分子基础。利用高通量激酶组阵列分析和先进的通路分析，我们确定了与调节自愿运动相关的蛋白激酶信号通路。使用基因本体论（GO）进行的通路分析显示，背侧纹状体中有155个GO术语发生了显著变化，海马体中有206个GO术语发生了显著变化。在运动组（自愿轮转跑步，VWR）和久坐对照组大鼠之间，纹状体和海马体中观察到激酶活性的变化。在这两个区域，与对照组大鼠相比，VWR大鼠的全局丝氨酸 - 苏氨酸激酶（STK）活性降低，而全局磷酸酪氨酸激酶（PTK）活性增加。我们还确定了VWR大鼠中发生改变的特定激酶，包括IκB激酶（IKK）和蛋白激酶δ（PKD）家族。C末端src激酶（CSK）、表皮生长因子（EGFR）和血管内皮生长因子受体（VEGFR）酪氨酸激酶也有所富集。这些发现表明自愿运动后激酶活性存在区域异质性，强调了运动行为潜在的分子机制。这项探索性研究为未来研究个体和不同性别之间运动效果差异的因果关系，以及开发促进身体活动和对抗相关慢性疾病的靶向干预措施奠定了基础。
