Loss of cell adhesion molecule CHL1 improves homeostatic adaptation and survival in hypoxic stress
作者单位：Institute of Molecular and Clinical MedicineKunming Medical College
会议名称：《中国神经科学学会第十届全国学术会议》
会议日期：2013年
学科分类：1001[医学-基础医学(可授医学、理学学位)] 10[医学]
关 键 词：CHL1 acute hypoxia homeostatic adaptation survival
摘 要：Objective CHLl is a transmembrane cell adhesion molecule that is critical for brain development and in the maintenance of neural circuits in the adult.Recent studies revealed that CHLl has diverse roles and is involved in the regulation of recovery after spinal cord injury.CHLl expression was down-regulated in the cerebral cortex,hypothalamus and brain stem after induction of acute hypoxia.In the current study we sought to address the role of CHLl in regulating homeostasis responses to hypoxia using CHLl knockout(CHLl) mice.Results We found that,compared with the wild type littermates,CHLl mice showed a dramatically lower mortality rate and an augmented ventilatory response after they were subjected to acute hypoxia.Immunofluorescence staining revealed that CHLl was expressed in the carotid body(CB),the key oxygen sensor in rodents and CHLl expression level in CB as assayed by western blot was decreased after hypoxic exposure.The number of glomus cells and the expression of tyrosine hydroxylase(TH,a marker for glomus cells) in CB of CHLl mice appeared to be increased compared with CHL1mice.In addition,in the ex vivo carotid body preparation,hypoxia induced a significantly greater afferent nerve discharge in CHLl mice compared with the CHL1 mice.Furthermore,the arterial blood pressure and plasma catecholamine level of CHLl mice were also significantly higher than those of CHL1 mice.Conclusion Our findings first demonstrate that CHLl is a novel intrinsic factor that is involved in carotid body function and in the ventilatory response to acute hypoxia.