肠道神经思维导图

U869751435

2025-04-16

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肠外神经元

肾上腺素受体

产生乙酰胆碱

肠道神经内容详述

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思维导图大纲

肠外神经元

somatosensory neurons体感神经元

Extrinsic gut-innervating sensory neurons外源性肠道感觉神经元胞体分布在结节状神经节和背根神经节nodose ganglia（NG）and dorsal root ganglia (DRG)

Extrinsic gut-innervating sensory neurons residing within the nodose ganglia and dorsal root ganglia (DRG) transduce sensory signals from the gut to the brainstem and spinal cord, respectively. These neurons are pseudo-unipolar in nature, with a peripheral axon that terminates in the end-organ such as the gut, and a central axon that terminates in the CNS. These sensory neuron populations detect nutrients, mechanical stretch, luminal threats, and immune stimuli including cytokines. These neurons also signal within the gut by their release of neuropeptides such as CGRP and substance P or non-peptidergic (not expressing SP or CGRP) from their peripheral nerve terminals.

Specialized subtypes of sensory neurons, such as proprioceptors, mechanoreceptors, thermoreceptors, and nociceptors (pain-mediating neurons), are tuned to detect specific stimuli. Their neuronal dendrites express receptors for various sensory stimuli, including noxious/harmful substances, as well as ion channels that rapidly transduce extracellular signals into intracellular calcium influx and action potentials. Nociceptors detect stimuli such as mechanical force, harmful temperatures or chemicals, injury-related signals, and microbial components.

Cre工具鼠

通过NAV1.8-Cre报告基因广泛标记肠道伤害性感受器，发现NAV1.8+神经元与黏液分泌型杯状细胞紧密相邻。51 值得注意的是，清除NAV1.8+神经元会导致黏液厚度显著减少，而使用DREADD（人工设计受体专一激活系统）选择性激活这些神经元足以诱导邻近杯状细胞分泌黏液。机制上，研究者发现NAV1.8+神经元通过释放降钙素基因相关肽（CGRP）调控黏液分泌，CGRP通过杯状细胞上的RAMP1受体传递信号。与无特定病原体（SPF）小鼠相比，无菌（GF）小鼠肠道中CGRP的基础分泌水平显著降低。在另一项互补研究中，DREADD介导的TRPV1+神经元沉默或化学清除均会加剧DSS结肠炎的菌群失调和疾病严重程度。

神经递质（肽类和非肽类）

除CGRP外，感觉神经元末梢致密核心囊泡还储存着由前速激肽原（Tac1）基因编码的P物质（SP）。多项研究证实，皮内注射SP足以诱发水肿、血管通透性增加、粒细胞募集及白细胞-血管内皮黏附增强等快速非特异性局部炎症反应。77,78但在肥大细胞缺陷小鼠中，这些反应完全消失，表明该先天免疫应答由局部肥大细胞激活/脱颗粒介导。SP作用于肥大细胞的疾病相关性在特应性皮炎（AD）模型中最为显著。

TRPV1+神经元释放的SP通过真皮树突细胞DC2s（dDC2）表面MRGPRA1受体促进其迁移至引流淋巴结，进而启动模型特征性Th2应答。这些范例揭示了神经元亚群（如TRPV1+SP+神经元与Mrgprd+谷氨酸+神经元）对皮肤免疫细胞功能的差异化调控，以及免疫系统将相同神经信号（SP）转化为不同效应（先天与适应性2型免疫激活）的整合能力。此类平行机制表明，宿主防御系统的强度与复杂性既是其进化优势，在自身炎症状态下也可能导致相应程度的病理损害。

采用带电利多卡因衍生物QX-314对NAV1.8+感觉神经元进行消融或靶向干预，可显著减轻OVA和HDM致敏小鼠模型中过敏原诱导的气道炎症（图3B）。值得注意的是，QX-314治疗在OVA诱导的哮喘小鼠模型中效果甚微，这表明伤害感受器对肺部炎症的影响存在模型依赖性差异。

autonomic neurons自主神经元

Sympathetic nervous system交感神经起源于脊髓

Diverts blood flow away from the gastro-intestinal (GI) tract and skin via vasoconstriction Blood flow to skeletal muscles and the lungs is enhanced (by as much as 1200% in the case of skeletal muscles) Dilates bronchioles of the lung through circulating epinephrine, which allows for greater alveolar oxygen exchange Increases heart rate and the contractility of cardiac cells (myocytes), thereby providing a mechanism for enhanced blood flow to skeletal muscles Dilates pupils and relaxes the ciliary muscle to the lens, allowing more light to enter the eye and enhances far vision Provides vasodilation for the coronary vessels of the heart Constricts all the intestinal sphincters and the urinary sphincter Inhibits peristalsis Stimulates orgasm

Sympathetic neurons signal via catecholamines (dopamine, epinephrine, norepinephrine) to α- or β-adrenergic receptors多巴胺、肾上腺素、去甲肾上腺素递质靶向α- or β-肾上腺素受体

Parasympathetic nervous system副交感神经起源于脑干

Dilating blood vessels leading to the GI tract, increasing the blood flow. Constricting the bronchiolar diameter when the need for oxygen has diminished Dedicated cardiac branches of the vagus and thoracic spinal accessory nerves impart parasympathetic control of the heart (myocardium) Constriction of the pupil and contraction of the ciliary muscles, facilitating accommodation and allowing for closer vision Stimulating salivary gland secretion, and accelerates peristalsis, mediating digestion of food and, indirectly, the absorption of nutrients Sexual. Nerves of the peripheral nervous system are involved in the erection of genital tissues via the pelvic splanchnic nerves 2–4. They are also responsible for stimulating sexual arousal.

parasympathetic neurons mainly originate in the brainstem, innervating the gut through the efferent vagus nerve, and mediate gut physiology via the neurotransmitter acetylcholine (ACh) in driving motility, digestion, and secretory function产生乙酰胆碱

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肠内神经元

Enteric neurons reside fully within the GI tract, and are organized into ganglionated networks encircling the intestinal tube and spatially categorized into two layers: the myenteric plexus, between the circular and longitudinal muscle layer, and the submucosal plexus in the submucosa. These two plexii are closely interconnected by interneurons, motor neurons, and enteric glial cells. Together, they form reflex circuits that mediate peristalsis and secretory function. In addition, they also integrate signals from extrinsic sensory, parasympathetic, and sympathetic neurons to mediate gut physiology

休克思维导图