Developmental nicotine exposure alters cholinergic control of respiratory frequency in neonatal rats.
Developmental nicotine exposure alters cholinergic control of respiratory frequency in neonatal rats.
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DOI：
10.1002/dneu.22380
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发表时间：
2016-10
影响因子：
3
通讯作者：
Fregosi RF
中科院分区：
文献类型：
--
作者：
Wollman LB;Haggerty J;Pilarski JQ;Levine RB;Fregosi RF
出生后第一周通过母乳持续接触尼古丁（发育性尼古丁暴露，DNE）会改变控制呼吸的脑干回路的发育。在这里，我们测试的假设，DNE改变呼吸运动反应内源性和外源性乙酰胆碱（ACh）在新生大鼠。我们使用的脑干脊髓制备的分裂浴配置，并施加药物的脑干室，同时测量的频率和振幅的第四颈腹神经根（C4 VR），其中包含膈运动神经元的轴突。我们单独应用ACh;烟碱型乙酰胆碱受体（nAChR）拮抗剂箭毒，单独使用或与ACh一起使用;以及毒蕈碱型乙酰胆碱受体（mAChR）拮抗剂阿托品，单独使用或与ACh一起使用。主要调查结果包括：1）阿托品在对照组和DNE动物中同样降低频率，而箭毒在对照组中引起适度的减慢，但在DNE动物中没有一致的变化; 2）DNE大大减弱了由外源性ACh介导的C4 VR频率的增加; 4）在阿托品存在的情况下，用ACh刺激nAChRs在对照组中显著增加频率，但在DNE动物中没有显著变化; 5）在箭毒存在下用ACh刺激mAChR引起频率的适度增加，没有治疗组差异。DNE钝化呼吸中枢模式发生器对外源性乙酰胆碱的反应，这与功能正常的乙酰胆碱受体的可用性降低一致; DNE没有改变呼吸运动输出的毒蕈碱控制。
Prenatal nicotine exposure with continued exposure through breast milk over the first week of life (developmental nicotine exposure, DNE) alters the development of brainstem circuits that control breathing. Here, we test the hypothesis that DNE alters the respiratory motor response to endogenous and exogenous acetylcholine (ACh) in neonatal rats. We used the brainstem-spinal cord preparation in the split-bath configuration, and applied drugs to the brainstem compartment while measuring the frequency and amplitude of the fourth cervical ventral nerve roots (C4VR), which contain the axons of phrenic motoneurons. We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh. The main findings include: 1) atropine reduced frequency similarly in controls and DNE animals, while curare caused modest slowing in controls but no consistent change in DNE animals; 2) DNE greatly attenuated the increase in C4VR frequency mediated by exogenous ACh; 4) stimulation of nAChRs with ACh in the presence of atropine increased frequency markedly in controls, but not DNE animals; 5) stimulation of mAChRs with ACh in the presence of curare caused a modest increase in frequency, with no treatment group differences. DNE blunts the response of the respiratory central pattern generator to exogenous ACh, consistent with reduced availability of functionally competent nAChRs; DNE did not alter the muscarinic control of respiratory motor output.