Data_Sheet_1_Sedentary Conditions Promote Subregionally Specific Changes in Brain-Derived Neurotrophic Factor in the Rostral Ventrolateral Medulla.PDF

A sedentary lifestyle is the top preventable cause of death and accounts for substantial socioeconomic costs to society. The rostral ventrolateral medulla regulates blood pressure under normal and pathophysiological states, and demonstrates inactivity-related structural and functional neuroplasticity, which is subregionally specific. The purpose of this study was to examine pro- and mature forms of brain-derived neurotrophic factor (BDNF) and their respective receptors in the male rat rostral ventrolateral medulla (RVLM) and its rostral extension following sedentary vs. active (running wheels) conditions (10–12weeks). We used subregionally specific Western blotting to determine that the mature form of BDNF and its ratio to its pro-form were lower in more caudal subregions of the rostral ventrolateral medulla of sedentary rats but higher in the rostral extension when both were compared to active rats. The full-length form of the tropomyosin receptor kinase B receptor and the non-glycosylated form of the 75 kilodalton neurotrophin receptor were lower in sedentary compared to active rats. The rostrocaudal patterns of expression of the mature form of BDNF and the full-length form of the tropomyosin receptor kinase B receptor were remarkably similar to the subregionally specific patterns of enhanced dendritic branching, neuronal activity, and glutamate-mediated increases in sympathetic nerve activity observed in previous studies performed in sedentary rats. Our studies suggest signaling pathways related to BDNF within subregions of both the rostral ventrolateral medulla and its rostral extension contribute to cardiovascular disease and premature death related to a sedentary lifestyle.

久坐的生活方式是导致死亡的首要可预防因素，并对社会造成巨大的社会经济成本。前脑室旁核在正常和病理生理状态下调节血压，并表现出与不活动相关的结构和功能神经可塑性，这种可塑性在亚区域内具有特异性。本研究旨在比较久坐与活跃（跑步轮）条件（10-12周）下，雄性大鼠前脑室旁核（RVLM）及其前延伸部分脑源性神经营养因子（BDNF）的促成熟形式及其相应受体的表达情况。我们采用亚区域特异性蛋白质印迹法确定，与活跃大鼠相比，久坐大鼠前脑室旁核更尾端的亚区域中BDNF的成熟形式及其与原形式的比率较低，而在两者进行比较时，其前延伸部分较高。肌动蛋白受体激酶B受体的全长形式和非糖基化形式的75千道尔顿神经营养因子受体在久坐大鼠中的表达低于活跃大鼠。BDNF成熟形式和肌动蛋白受体激酶B受体全长形式的头尾表达模式与前脑室旁核及其前延伸部分亚区域内增强树突分支、神经元活性和谷氨酸介导的交感神经活动增加的亚区域特异性模式惊人地相似，这些亚区域特异性模式是在先前针对久坐大鼠进行的研究中观察到的。我们的研究结果表明，与BDNF相关的信号通路在脑室旁核及其前延伸部分的亚区域内均参与导致久坐生活方式相关的心血管疾病和过早死亡。