Hypothalamic orexins/hypocretins as regulators of breathing-猫眼课题宝

下丘脑食欲素/下丘脑分泌素作为呼吸调节剂

DOI：

发表时间：

2008

期刊：

Expert Reviews in Molecular Medicine

影响因子：

6.2

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

Rhîannan H. Williams;D. Burdakov

半个世纪前就有人提出，来自下丘脑外侧区的电脉冲刺激呼吸。现在出现的是，这些作用可能是介导的，至少部分是由含有食欲素神经肽（也称为hypocretins）的神经元。这些细胞促进觉醒和意识，它们的丧失导致嗜睡症。最近的数据还表明，食欲素神经元直接投射到脑干中的呼吸中心，该呼吸中心表达食欲素受体，并且在那里注射食欲素刺激呼吸。由于食欲素神经元接收的输入信号是代谢、睡眠/觉醒和情绪状态，因此很容易推测它们可能根据这些参数调节呼吸。敲除小鼠的食欲素基因可使二氧化碳诱导的呼吸增加减少约50%，并增加自发性睡眠呼吸暂停的频率。食欲素和呼吸之间的关系可能是双向的：呼吸速率控制酸和CO2水平，这些信号改变体外食欲素神经元的电活动。总体而言，这些发现表明食欲素对呼吸调节很重要，并可能在呼吸系统疾病的病理生理学和医学治疗中发挥作用。

It was suggested half a century ago that electrical impulses from the lateral hypothalamic area stimulate breathing. It is now emerging that these effects may be mediated, at least in part, by neurons containing orexin neuropeptides (also known as hypocretins). These cells promote wakefulness and consciousness, and their loss results in narcolepsy. Recent data also show that orexin neurons directly project to respiratory centres in the brainstem, which express orexin receptors, and where injection of orexin stimulates breathing. Because orexin neurons receive inputs that signal metabolic, sleep/wake and emotional states, it is tempting to speculate that they may regulate breathing according to these parameters. Knockout of the orexin gene in mice reduces CO2-induced increases in breathing by ∼50% and increases the frequency of spontaneous sleep apneas. The relationship between orexins and breathing may be bidirectional: the rate of breathing controls acid and CO2 levels, and these signals alter the electrical activity of orexin neurons in vitro. Overall, these findings suggest that orexins are important for the regulation of breathing and may potentially play a role in the pathophysiology and medical treatment of respiratory disorders.