PDF(Pubmed)
Abstract：
Orexin signaling plays a facilitatory role in respiration. Abnormalities in orexin levels correlate with disordered breathing patterns and impaired central respiratory chemoreception. Nucleus tractus solitarii (NTS) neurons expressing the transcription factor Phox2b contribute to the chemoreceptive regulation of respiration. However, the extent to which orexinergic signaling modulates respiratory activity in these Phox2b-expressing NTS neurons remains unclear. In the present study, the injection of orexin A into the NTS significantly increased the firing rate of the phrenic nerve. Further analysis using fluorescence in situ hybridization and immunohistochemistry revealed that orexin 1 receptors (OX1Rs) were primarily located in the ventrolateral subdivision of the NTS and expressed in 25% of Phox2b-expressing neurons. Additionally, electrophysiological recordings showed that exposure to orexin A increased the spontaneous firing rate of Phox2b-expressing neurons. Immunostaining experiments with cFos revealed that the OX1R-residing Phox2b-expressing neurons were activated by an 8% CO2 stimulus. Crucially, OX1R knockdown in these NTS neurons notably blunted the ventilatory response to 8% CO2, alongside an increase in sigh-related apneas. In conclusion, orexinergic signaling in the NTS facilitates breathing through the activation of OX1Rs, which induces the depolarization of Phox2b-expressing neurons. OX1Rs are essential for the involvement of Phox2b-expressing NTS neurons in the hypercapnic ventilatory response.
摘要：
食欲素信号在呼吸中起促进作用。食欲素水平异常与呼吸模式紊乱和中枢呼吸化学感受受损相关。表达转录因子Phox2b的孤束核（NTS）神经元有助于呼吸的化学感受调节。然而,在这些表达Phox2b的NTS神经元中,食欲素能信号调节呼吸活动的程度尚不清楚.在本研究中,向NTS中注射食欲素A可显着提高the神经的放电率。使用荧光原位杂交和免疫组织化学进行的进一步分析显示，食欲素1受体（OX1R）主要位于NTS的腹外侧细分中，并在25％的Phox2b表达神经元中表达。此外,电生理记录表明，暴露于食欲素A会增加表达Phox2b的神经元的自发放电率。用cFos进行的免疫染色实验表明，驻留OX1R的Phox2b表达神经元被8％CO2刺激激活。至关重要的是，这些NTS神经元中的OX1R敲除明显减弱了对8％CO2的通气反应，同时增加了与叹息相关的呼吸暂停。总之,NTS中的orexinine能信号通过激活OX1R促进呼吸，诱导表达Phox2b的神经元去极化。OX1R对于表达Phox2b的NTS神经元参与高碳酸血症通气反应至关重要。
