Fyk-Kolodziej Bozena E, Mueller Patrick J
Department of Physiology, Wayne State University School of Medicine, Detroit, MI, United States.
Front Physiol. 2021 Oct 13;12:756542. doi: 10.3389/fphys.2021.756542. eCollection 2021.
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.
久坐不动的生活方式是可预防的首要死亡原因，给社会带来了巨大的社会经济成本。延髓头端腹外侧区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，且具有亚区域特异性。本研究的目的是检测雄性大鼠在久坐与活跃（跑轮）状态（10 - 12周）下，延髓头端腹外侧区（RVLM）及其头端延伸区域中脑源性神经营养因子（BDNF）的前体和成熟形式及其各自的受体。我们使用亚区域特异性蛋白质免疫印迹法确定，与活跃大鼠相比，久坐大鼠延髓头端腹外侧区更靠尾侧的亚区域中BDNF的成熟形式及其与前体形式的比率较低，但在头端延伸区域较高。与活跃大鼠相比，久坐大鼠中肌钙蛋白受体激酶B受体的全长形式和75千道尔顿神经营养因子受体的非糖基化形式较低。BDNF成熟形式和肌钙蛋白受体激酶B受体全长形式的 rostrocaudal 表达模式与先前在久坐大鼠中进行的研究中观察到的树突分支增强、神经元活动以及谷氨酸介导的交感神经活动增加的亚区域特异性模式非常相似。我们的研究表明，延髓头端腹外侧区及其头端延伸区域的亚区域内与BDNF相关的信号通路促成了与久坐生活方式相关的心血管疾病和过早死亡。
