介导高碳酸血症诱导的微觉醒和睡眠深度受损的神经环路
Neural circuitry mediating hypercapnia-induced microarousal and impaired sleep depth.
文献信息
| PMID | 42912997 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Chen Yang |
| 作者单位 | Department of General Practice, Department of Geriatric Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Joint International Research Laboratory of Sleep, Fudan University, Shanghai 200040, China. |
| 期刊 | Science advances |
| SCI 分区 | Q1 |
| IF | 14.8 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 耳科 |
中文摘要
背景： 阻塞性睡眠呼吸暂停综合征中的睡眠破坏以频繁微觉醒和睡眠深度降低为特征，但其潜在机制仍不清楚。结果：在此，我们显示间歇性高碳酸血症空气（HA）诱导时间锁定的微觉醒、使睡眠碎片化、降低非快速眼动（NREM）睡眠深度，并减少快速眼动（REM）睡眠。HA暴露激活孤束核中的谷氨酸能神经元（NTSVglut2），其光遗传学或化学遗传学激活足以触发觉醒并损害睡眠。投射特异性激活揭示，NTSVglut2向室旁核（PVN）、臂旁核（PB）、室旁丘脑和蓝斑（LC）的投射促进觉醒，而向PB和LC的投射还降低NREM睡眠深度。抑制NTSVglut2向PVN的投射显著推迟HA诱导的觉醒。NTSVglut2终末单突触激活PVN中的促肾上腺皮质激素释放激素神经元（PVNCRH），而抑制PVNCRH神经元或敲低Slc17a6（编码Vglut2）而非Crh，会延迟高碳酸血症诱导的觉醒。结论：这些发现确定了高碳酸血症诱导的微觉醒和睡眠深度降低背后的神经环路。
英文摘要
Sleep disruption in obstructive sleep apnea syndrome is characterized by frequent microarousals and reduced sleep depth, yet the underlying mechanisms remain unclear. Here, we show that intermittent hypercapnic air (HA) induces time-locked microarousals, fragments sleep, reduces non-rapid eye movement (NREM) sleep depth, and diminishes rapid eye movement (REM) sleep. HA exposure activates glutamatergic neurons in the nucleus tract solitary (NTSVglut2), and their optogenetic or chemogenetic activation is sufficient to trigger arousal and impair sleep. Projection-specific activation reveals that NTSVglut2 projections to the paraventricular nucleus (PVN), parabrachial nucleus (PB), paraventricular thalamus, and locus coeruleus (LC) promote arousal, whereas projections to the PB and LC additionally reduce NREM sleep depth. Inhibition of NTSVglut2 projection to the PVN significantly postpones HA-induced arousal. NTSVglut2 terminals monosynaptically activate corticotropin-releasing hormone neurons in the PVN (PVNCRH), and inhibition of PVNCRH neurons or knockdown of Slc17a6 (encoding Vglut2), but not Crh, delays hypercapnia-induced arousal. These findings identify neural circuits underlying hypercapnia-induced microarousal and reduced sleep depth.