Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682022, Kerala, India.
Biochem Cell Biol. 2013 Oct;91(5):350-6. doi: 10.1139/bcb-2012-0102. Epub 2013 Apr 26.
Molecular processes regulating cholinergic functions play an important role in the control of respiration under hypoxia. Cholinergic alterations and its further complications in respiration due to hypoxic insult in neonatal rats and the effect of glucose, oxygen, and epinephrine resuscitation was evaluated in the present study. Receptor binding and gene expression studies were done in the corpus striatum to analyse the changes in total muscarinic receptors, muscarinic M1, M2, M3 receptors, and the enzymes involved in acetylcholine metabolism, choline acetyltransferase and acetylcholinesterase. Neonatal hypoxia decreased total muscarinic receptors with reduced expression of muscarinic M1, M2, and M3 receptor genes. The reduction in acetylcholine metabolism is indicated by the downregulated choline acetyltransferase and upregulated acetyl cholinesterase expression. These cholinergic disturbances were reversed to near control in glucose-resuscitated hypoxic neonates. The adverse effects of immediate oxygenation and epinephrine administration are also reported. The present findings points to the cholinergic alterations due to neonatal hypoxic shock and suggests a proper resuscitation method to ameliorate these striatal changes.
调节胆碱能功能的分子过程在缺氧下的呼吸控制中起着重要作用。本研究评估了新生大鼠缺氧损伤引起的胆碱能改变及其对呼吸的进一步并发症，以及葡萄糖、氧气和肾上腺素复苏的影响。在纹状体进行受体结合和基因表达研究，以分析总毒蕈碱受体、毒蕈碱 M1、M2、M3 受体以及参与乙酰胆碱代谢的酶（胆碱乙酰转移酶和乙酰胆碱酯酶）的变化。新生儿缺氧导致总毒蕈碱受体减少，毒蕈碱 M1、M2 和 M3 受体基因表达减少。乙酰胆碱代谢的减少表明胆碱乙酰转移酶下调和乙酰胆碱酯酶上调。葡萄糖复苏的缺氧新生儿中，这些胆碱能紊乱几乎恢复到对照水平。还报告了立即给氧和肾上腺素给药的不良影响。目前的研究结果表明，由于新生儿缺氧性休克导致的胆碱能改变，并提出了一种适当的复苏方法来改善这些纹状体变化。
