Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Department of Anesthesiology, Wayne State University School of Medicine, Detroit, Michigan, USA.
J Comp Neurol. 2021 Jun;529(9):2311-2331. doi: 10.1002/cne.25094. Epub 2021 Jan 6.
The rostral ventrolateral medulla (RVLM) is a brain region involved in normal regulation of the cardiovascular system and heightened sympathoexcitatory states of cardiovascular disease (CVD). Among major risk factors for CVD, sedentary lifestyles contribute to higher mortality than other modifiable risk factors. Previous studies suggest excessive glutamatergic excitation of presympathetic neurons in the RVLM occurs in sedentary animals. Therefore, the purpose of this study was to examine neuroplasticity in the glutamatergic system in the RVLM of sedentary and physically active rats. We hypothesized that relative to active rats, sedentary rats would exhibit higher expression of glutamate N-methyl-d-aspartic acid receptor subunits (GluN), phosphoGluN1, and the excitatory scaffold protein postsynaptic density 95 (PSD95), while achieving higher glutamate levels. Male Sprague-Dawley rats (4 weeks old) were divided into sedentary and active (running wheel) conditions for 10-12 weeks. We used retrograde tracing/triple-labeling techniques, western blotting, and magnetic resonance spectroscopy. We report in sedentary versus physically active rats: 1) fewer bulbospinal non-C1 neurons positive for GluN1, 2) significantly higher expression of GluN1 and GluN2B but lower levels of phosphoGluN1 (pSer896) and PSD95, and 3) higher levels of glutamate in the RVLM. Higher GluN expression is consistent with enhanced sympathoexcitation in sedentary animals; however, a more complex neuroplasticity occurs within subregions of the ventrolateral medulla. Our results in rodents may also indicate that alterations in glutamatergic excitation of the RVLM contribute to the increased incidence of CVD in humans who lead sedentary lifestyles. Thus, there is a strong need to further pursue mechanisms of inactivity-related neuroplasticity in the RVLM.
延髓头端腹外侧区（RVLM）是一个参与心血管系统正常调节和心血管疾病（CVD）交感兴奋状态的脑区。在 CVD 的主要危险因素中，久坐的生活方式比其他可改变的危险因素导致更高的死亡率。先前的研究表明，在久坐的动物中，RVLM 中的交感前神经元过度谷氨酸能兴奋。因此，本研究旨在研究久坐和活跃大鼠 RVLM 中谷氨酸能系统的神经可塑性。我们假设与活跃大鼠相比，久坐大鼠的谷氨酸 N-甲基-D-天冬氨酸受体亚基（GluN）、磷酸化 GluN1 和兴奋性支架蛋白突触后密度 95（PSD95）表达更高，同时谷氨酸水平更高。雄性 Sprague-Dawley 大鼠（4 周龄）被分为久坐和活跃（跑步轮）条件 10-12 周。我们使用逆行示踪/三重标记技术、Western 印迹和磁共振波谱。与活跃大鼠相比，我们报告在久坐大鼠中：1）少部分 RVLM 中的 bulbospinal 非 C1 神经元 GluN1 阳性，2）GluN1 和 GluN2B 表达显著升高，但磷酸化 GluN1（pSer896）和 PSD95 水平降低，3）RVLM 中谷氨酸水平升高。更高的 GluN 表达与久坐动物的交感兴奋增强一致；然而，在腹外侧 medulla 的亚区中发生了更复杂的神经可塑性。我们在啮齿动物中的结果也可能表明，RVLM 中谷氨酸能兴奋的改变导致了久坐生活方式的人类 CVD 发病率增加。因此，强烈需要进一步研究 RVLM 中与不活动相关的神经可塑性的机制。
