Department of Neural and Behavioral Sciences, Penn State, College of Medicine , Hershey, Pennsylvania.
Am J Physiol Gastrointest Liver Physiol. 2018 Apr 1;314(4):G504-G516. doi: 10.1152/ajpgi.00382.2017. Epub 2018 Jan 11.
Chronic stress exerts vagally dependent effects to disrupt gastric motility; previous studies have shown that, among other nuclei, A2 neurons are involved in mediating these effects. Several studies have also shown robust in vitro and in vivo effects of α2-adrenoceptor agonists on vagal motoneurons. We have demonstrated previously that brainstem vagal neurocircuits undergo remodeling following acute stress; however, the effects following brief periods of chronic stress have not been investigated. Our aim, therefore, was to test the hypothesis that different types of chronic stress influence gastric tone and motility by inducing plasticity in the response of vagal neurocircuits to α-adrenoreceptor agonists. In rats that underwent 5 days of either homotypic or heterotypic stress loading, we applied the α-adrenoceptor agonist, UK14304, either by in vitro brainstem perfusion to examine its ability to modulate GABAergic synaptic inputs to vagal motoneurons or in vivo brainstem microinjection to observe actions to modulate antral tone and motility. In neurons from naïve rats, GABAergic currents were unresponsive to exogenous application of UK14304. In contrast, GABAergic currents were inhibited by UK14304 in all neurons from homotypic and, in a subpopulation of neurons, heterotypic stressed rats. In control rats, UK14304 microinjection inhibited gastric tone and motility via withdrawal of vagal cholinergic tone; in heterotypic stressed rats, the larger inhibition of antrum tone was due to a concomitant activation of peripheral nonadrenergic, noncholinergic pathways. These data suggest that stress induces plasticity in brainstem vagal neurocircuits, leading to an upregulation of α-mediated responses. NEW & NOTEWORTHY Catecholaminergic neurons of the A2 area play a relevant role in stress-related dysfunction of the gastric antrum. Brief periods of chronic stress load induce plastic changes in the actions of adrenoceptors on vagal brainstem neurocircuits.
慢性应激通过迷走神经依赖的方式干扰胃动力；先前的研究表明，A2 神经元在介导这些效应中起重要作用。几项研究还表明，α2-肾上腺素受体激动剂对迷走运动神经元具有强大的体外和体内作用。我们之前已经证明，急性应激后脑干迷走神经回路会发生重塑；然而，短暂慢性应激后的影响尚未得到研究。因此，我们的目的是检验以下假设：通过诱导迷走神经回路对 α-肾上腺素受体激动剂反应的可塑性，不同类型的慢性应激会影响胃张力和运动。在经历 5 天同型或异型应激负荷的大鼠中，我们通过体外脑干灌流应用 α-肾上腺素受体激动剂 UK14304，以观察其调节迷走运动神经元 GABA 能突触传入的能力，或通过体内脑干微注射观察其调节胃窦张力和运动的作用。在未受应激的大鼠神经元中，外源性 UK14304 不能引起 GABA 电流反应。相比之下，在同型应激和异型应激大鼠的所有神经元中，GABA 电流都被 UK14304 抑制，而在异型应激大鼠的亚群神经元中，GABA 电流被抑制。在对照大鼠中，UK14304 微注射通过撤回迷走胆碱能张力抑制胃窦张力和运动；在异型应激大鼠中，胃窦张力的更大抑制是由于外周非肾上腺素能、非胆碱能途径的同时激活。这些数据表明，应激诱导脑干迷走神经回路的可塑性，导致 α 介导的反应上调。新的和值得注意的是：A2 区的儿茶酚胺能神经元在胃窦应激相关功能障碍中起重要作用。短暂的慢性应激负荷会导致迷走神经脑干神经回路中肾上腺素受体作用的可塑性变化。
