Zellner Leor C, Brundage Kathleen M, Hunter Dawn D, Dey Richard D
4052 Health Sciences Center North, PO Box 9128, Morgantown, WV 26506-9128, .
Toxicol Environ Chem. 2011 Jan 1;93(10):2055-2071. doi: 10.1080/02772248.2011.610882.
Sensory neurons originating in nodose and jugular ganglia that innervate airway epithelium (airway neurons) play a role in inflammation observed following exposure to inhaled environmental irritants such as ozone (O(3)). Airway neurons can mediate airway inflammation through release of the neuropeptide substance P (SP). While susceptibility to airway irritants is increased in early life, the developmental dynamics of afferent airway neurons are not well characterized. The hypothesis of this study was that airway neuron number might increase with increasing age, and that an acute, early postnatal O(3) exposure might increase both the number of sensory airway neurons as well as the number SP-containing airway neurons. Studies using Fischer 344 rat pups were conducted to determine if age or acute O(3) exposure might alter airway neuron number. Airway neurons in nodose and jugular ganglia were retrogradely labeled, removed, dissociated, and counted by means of a novel technique employing flow cytometry. In Study 1, neuron counts were conducted on postnatal days (PD) 6, 10, 15, 21, and 28. Numbers of total and airway neurons increased significantly between PD6 and PD10, then generally stabilized. In Study 2, animals were exposed to O(3) (2 ppm) or filtered air (FA) on PD5 and neurons were counted on PD10, 15, 21, and 28. O(3) exposed animals displayed significantly less total neurons on PD21 than FA controls. This study shows that age-related changes in neuron number occur, and that an acute, early postnatal O(3) exposure significantly alters sensory neuron development.
起源于结状神经节和颈静脉神经节并支配气道上皮的感觉神经元（气道神经元），在暴露于吸入性环境刺激物（如臭氧（O₃））后所观察到的炎症中发挥作用。气道神经元可通过释放神经肽P物质（SP）来介导气道炎症。虽然生命早期对气道刺激物的易感性会增加，但传入气道神经元的发育动态尚未得到很好的描述。本研究的假设是，气道神经元数量可能会随着年龄的增长而增加，并且出生后早期急性暴露于臭氧可能会增加感觉气道神经元的数量以及含SP的气道神经元的数量。使用Fischer 344大鼠幼崽进行研究，以确定年龄或急性臭氧暴露是否会改变气道神经元数量。通过一种采用流式细胞术的新技术，对结状神经节和颈静脉神经节中的气道神经元进行逆行标记、移除、解离并计数。在研究1中，在出生后第（PD）6、10、15、21和28天进行神经元计数。在PD6和PD10之间，总神经元和气道神经元的数量显著增加，然后总体稳定。在研究2中，动物在PD5时暴露于臭氧（2 ppm）或过滤空气（FA），并在PD10、15、21和28天对神经元进行计数。与FA对照组相比，暴露于臭氧的动物在PD21时的总神经元数量显著减少。本研究表明，神经元数量存在与年龄相关的变化，并且出生后早期急性暴露于臭氧会显著改变感觉神经元的发育。
