Intermittent hypercapnic hypoxia effects on the nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem |
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| Institution: | 1. The BOSCH Institute, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia;2. Department of Medicine, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia;3. Discipline of Pharmacology, Blackburn Building, D06, University of Sydney, NSW 2006, Australia;4. The Children’s Hospital, Westmead, Sydney, NSW 2145, Australia;1. Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou 310029, China;2. Department of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, MI48824, USA;3. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada;4. Sechenov Institute of Evolutionary Physiology & Biochemistry, Russian Academy of Sciences, St. Petersburg 194223, Russia;1. Developmenatl Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group CSIR – Indian Institute of Toxicology Research, Post Box 80, 31 MG Marg Lucknow – 226 001, India;2. Department of Biochemistry, Integral Institute of Medical Sciences & Research Integral University Lucknow – 226 026, India;3. Department of Biostatistics and Health Informatics Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow – 226 014, India;4. Department of Bioengineering, Faculty of Engineering Integral University, Lucknow – 226 026, India;1. College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, South Korea;2. Anydoctor Healthcare Co., Ltd., Cheonan, Chungnam 31066, South Korea;3. College of Veterinary Medicine, Chonnam National University, Gwangju 61186, South Korea;1. Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198-3135, USA;2. Havlik-Wall Professor of Oncology |
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| Abstract: | 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: 1 day IHH (1D IHH, n = 9), 4 days IHH (4D IHH, n = 8), controls exposed only to air cycles for 1 day (1D Air, n = 6) or 4 days (4D Air, n = 5), and pre-exposed to nicotine for 13 days prior to 1 day IHH (Nic + 1D IHH, n = 7). The exposure period alternated 6 min of HH (8%O2, 7%CO2, balance N2) and 6 min of air over 48 min, 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. |
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| Keywords: | Cigarette smoke Sudden infant death syndrome Obstructive sleeep apnea nAChR Medulla oblongata |
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