Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Am J Physiol Regul Integr Comp Physiol. 2024 Oct 1;327(4):R423-R441. doi: 10.1152/ajpregu.00293.2023. Epub 2024 Aug 5.
There is evidence that astrocytes modulate synaptic transmission in the nucleus tractus solitarius (NTS) interacting with glutamatergic and purinergic mechanisms. Here, using in situ working heart-brainstem preparations, we evaluated the involvement of astrocyte and glutamatergic/purinergic neurotransmission in the processing of autonomic and respiratory pathways in the NTS of control and rats exposed to sustained hypoxia (SH). Baseline autonomic and respiratory activities and the responses to chemoreflex activation (KCN) were evaluated before and after microinjections of fluorocitrate (FCt, an astrocyte metabolic inhibitor), kynurenic acid, and pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (PPADS) (nonselective antagonists of glutamatergic and purinergic receptors) into the rostral aspect of the caudal commissural NTS. FCt had no effects on the baseline parameters evaluated but reduced the bradycardic response to chemoreflex activation in SH rats. FCt combined with kynurenic acid and PPADS in control rats reduced the baseline duration of expiration, which was attenuated after SH. FCt produced a large increase in PN frequency discharge in control rats, which was reduced after SH, indicating a reduction in the astrocyte modulation after SH. The data show that ) the bradycardic component of the peripheral chemoreflex is reduced in SH rats after astrocytes inhibition, ) the inhibition of astrocytes in the presence of double antagonists in the NTS affects the modulation of baseline duration of expiration in control but not in SH rats, and ) the autonomic and respiratory responses to chemoreflex activation are mediated by glutamatergic and purinergic receptors in the rostral aspect of the caudal commissural NTS. Our findings indicate that the neurotransmission of autonomic and respiratory components of the peripheral chemoreflex in the nucleus tractus solitarius (NTS) is mediated by glutamatergic and purinergic mechanisms and reveal a selective involvement of NTS astrocytes in controlling the chemoreflex parasympathetic response in rats exposed to sustained hypoxia (SH) and the baseline duration of expiration mainly in control rats, indicating a selective role for astrocytes modulation in the NTS of control and SH rats.
有证据表明，星形胶质细胞通过与谷氨酸能和嘌呤能机制相互作用来调节孤束核（NTS）中的突触传递。在这里，我们使用原位心脏-脑干制备物，评估了星形胶质细胞和谷氨酸能/嘌呤能神经传递在控制和暴露于持续缺氧（SH）的大鼠 NTS 中自主和呼吸途径处理中的作用。在 NTS 腹侧后连合的前区注射氟柠檬酸（FCt，星形胶质细胞代谢抑制剂）、犬尿氨酸和吡哆醛-6-偶氮苯-2'，4'-二磺酸钠（PPADS）（谷氨酸能和嘌呤能受体的非选择性拮抗剂）前后，评估了自主和呼吸活动的基线以及对化学反射激活（KCN）的反应。FCt 对评估的基线参数没有影响，但降低了 SH 大鼠化学反射激活的心动过缓反应。FCt 与犬尿氨酸和 PPADS 联合应用于对照组大鼠，降低了基础呼气时间，SH 后则减弱。FCt 在对照组大鼠中产生了 PN 频率放电的大幅增加，SH 后减少，表明 SH 后星形胶质细胞调节减少。数据表明，) 在星形胶质细胞抑制后，SH 大鼠外周化学反射的心动过缓成分减少，) 在 NTS 中存在双拮抗剂时抑制星形胶质细胞，影响对照组但不影响 SH 大鼠基础呼气时间的调节，) 对化学反射激活的自主和呼吸反应是由 NTS 腹侧后连合的前区的谷氨酸能和嘌呤能受体介导的。我们的研究结果表明，孤束核（NTS）中自主和呼吸成分的外周化学反射的神经传递是由谷氨酸能和嘌呤能机制介导的，并揭示了 NTS 星形胶质细胞在控制持续缺氧（SH）大鼠和对照组大鼠基础呼气时间的化学反射副交感反应中的选择性参与，表明 NTS 星形胶质细胞调节在控制和 SH 大鼠中的选择性作用。
