Proteinase-activated receptors in the nucleus of the solitary tract: evidence for glial-neural interactions in autonomic control of the stomach.
Proteinase-activated receptors in the nucleus of the solitary tract: evidence for glial-neural interactions in autonomic control of the stomach.
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DOI：
10.1523/jneurosci.6063-08.2009
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发表时间：
2009-07-22
期刊：
影响因子：
--
通讯作者：
Rogers RC
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文献类型：
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作者：
Hermann GE;Van Meter MJ;Rood JC;Rogers RC
头部损伤出血与胃瘀滞有关；库欣在 1932 年左右描述了肠道自主控制崩溃的症状。最近的研究表明，继发于出血的蛋白酶凝血酶可能是根本原因。我们的体内生理研究结果表明，第四心室注射 PAR1 激动剂以及凝血酶本身，可使清醒大鼠的胃转运显着减少。我们预计 PAR1 抑制胃转运的作用是直接作用于背髓质迷走神经反射回路的结果。令人惊讶的是，我们的免疫组织化学研究表明 PAR1 受体仅定位于星形胶质细胞，而不是孤束核中的神经元 [NST;整合内脏传入输入和部分胃迷走神经反射控制电路的主要轨迹]。我们对后脑切片的体外钙成像研究表明，PAR1 激活最初会导致星形胶质细胞钙的急剧增加，几秒钟后 NST 神经元中钙信号的增加。 PAR1 激活的神经元效应（但不是星形胶质细胞效应）被谷氨酸受体拮抗作用消除。 TTX 并没有消除 PAR1 激活对神经胶质细胞或神经元的影响。因此，我们认为神经胶质细胞是 PAR 激动剂的主要中枢神经系统传感器，并且这些神经胶质细胞的反应驱动邻近的 [例如 NST] 神经元的活动。这些结果首次表明，自主控制的变化可以通过神经胶质细胞对局部化学刺激的检测直接发出信号。
Bleeding head injury is associated with gastric stasis; a symptom of collapse of autonomic control of the gut described by Cushing around 1932. Recent work suggests that the proteinase thrombin, produced secondary to bleeding, may be the root cause. Results from our in vivo physiological studies show that fourth ventricular injection of PAR1 agonists, as well as thrombin itself, produced significant reductions in gastric transit in the awake rat. We expected that the PAR1 effect to inhibit gastric transit was the result of direct action on vago-vagal reflex circuitry in the dorsal medulla. Surprisingly, our immunohistochemical studies demonstrated that PAR1 receptors are localized exclusively to the astrocytes and not the neurons in the nucleus of the solitary tract [NST; principal locus integrating visceral afferent input and part of the gastric vago-vagal reflex control circuitry]. Our in vitro calcium imaging studies of hindbrain slices revealed that PAR1 activation initially causes a dramatic increase in astrocytic calcium, followed seconds later by an increase in calcium signal in NST neurons. The neuronal effect, but not the astrocytic effect, of PAR1 activation was eliminated by glutamate receptor antagonism. TTX did not eliminate the effects of PAR1 activation on either glia or neurons. Thus, we propose that glia are the primary CNS sensors for PAR agonists and that the response of these glial cells drives the activity of adjacent [e.g., NST] neurons. These results show, for the first time, that changes in autonomic control can be directly signaled by glial detection of local chemical stimuli.