Vivekanandarajah Arunnjah, Aishah Atqiya, Waters Karen A, Machaalani Rita
The BOSCH Institute, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia; Department of Medicine, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia.
The BOSCH Institute, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia; Discipline of Pharmacology, Blackburn Building, D06, University of Sydney, NSW 2006, Australia.
Neurotoxicology. 2017 May;60:23-33. doi: 10.1016/j.neuro.2017.02.011. Epub 2017 Feb 22.
This study investigated the effects of acute (1 day) vs repeated (4 days) exposure to intermittent hypercapnic hypoxia (IHH) on the immunohistochemical expression of α2, α3, α5, α7, α9 and β2 nicotinic acetylcholine receptor (nAChR) subunits in the developing piglet hippocampus and brainstem medulla, and how prior nicotine exposure alters the response to acute IHH. Five piglet groups included: 1day IHH (1D IHH, n=9), 4days IHH (4D IHH, n=8), controls exposed only to air cycles for 1day (1D Air, n=6) or 4days (4D Air, n=5), and pre-exposed to nicotine for 13days prior to 1day IHH (Nic+1D IHH, n=7). The exposure period alternated 6min of HH (8%O, 7%CO, balance N) and 6min of air over 48min, while controls were switched from air-to-air. Results showed that: 1. repeated IHH induces more changes in nAChR subunit expression than acute IHH in both the hippocampus and brainstem medulla, 2. In the hippocampus, α2 and β2 changed the most (increased) following IHH and the CA3, CA2 and DG were mostly affected. In the brainstem medulla, α2, α5, α9 and β2 were changed (decreased) in most nuclei with the hypoglossal and nucleus of the solitary tract being mostly affected. 3. Pre-exposure to nicotine enhanced the changes in the hippocampus but dampened those in the brainstem medulla. These findings indicate that the nAChRs (predominantly with the α2/β2 complex) are affected by IHH in critical hippocampal and brainstem nuclei during early brain development, and that pre-exposure to nicotine alters the pattern of susceptibility to IHH.
本研究调查了急性（1天）与反复（4天）暴露于间歇性高碳酸血症性缺氧（IHH）对发育中小猪海马体和脑干延髓中α2、α3、α5、α7、α9和β2烟碱型乙酰胆碱受体（nAChR）亚基免疫组化表达的影响，以及先前的尼古丁暴露如何改变对急性IHH的反应。五个仔猪组包括：1天IHH组（1D IHH，n = 9）、4天IHH组（4D IHH，n = 8）、仅暴露于空气循环1天的对照组（1D Air，n = 6）或4天的对照组（4D Air，n = 5），以及在1天IHH之前预先暴露于尼古丁13天的组（Nic + 1D IHH，n = 7）。暴露期在48分钟内交替进行6分钟的HH（8%O₂、7%CO₂，其余为N₂）和6分钟的空气，而对照组则在空气与空气之间切换。结果表明：1. 在海马体和脑干延髓中，反复IHH比急性IHH诱导nAChR亚基表达的变化更多；2. 在海马体中，α2和β2在IHH后变化最大（增加），CA3、CA2和齿状回受影响最大。在脑干延髓中，大多数核中的α2、α5、α9和β2发生变化（减少），舌下神经核和孤束核受影响最大；3. 预先暴露于尼古丁增强了海马体中的变化，但减弱了脑干延髓中的变化。这些发现表明，在脑发育早期，nAChR（主要是α2/β2复合体）在关键的海马体和脑干核中受IHH影响，并且预先暴露于尼古丁会改变对IHH的易感性模式。
