a Department of Life Sciences , Sophia College-Autonomous , Mumbai , India.
b Department of Biology & Biochemistry , University of Bath , Bath , United Kingdom.
Int J Neurosci. 2019 Sep;129(9):864-870. doi: 10.1080/00207454.2019.1576662. Epub 2019 Mar 20.
Hypoxia-inducible factor 1 (HIF-1) is a key transcription factor in the detection of low oxygen levels, inducing expression of genes involved in mediating the response to hypoxia to maintain cellular oxygen homeostasis. is a soil nematode that has evolved specialized chemosensory neurons that detect changes in oxygen levels and guide its behaviour and responses to food. The role of the gene in modifying chemosensory behaviour in response to chemical hypoxia however remains unclear. Furthermore, the role of epigenetic modifiers in mediating this behavioural response to hypoxia is unclear. Our study addresses two questions (a) Do hypoxia-mimetics modify worm behaviour and (b) Are these behaviours modulated by HIF-dependent expression of epigenetic regulators? This study used established behavioural paradigms in mutant strains of , to study responses to chemical hypoxia. We show that exposure to the hypoxia-mimetic, sodium sulphite, changes the gustatory responses, chemotaxis, gustatory plasticity and associative conditioning behaviour. Longer-term exposure to hypoxia changes the behavioural response of wild type , mediated by the HIF pathway. Epigenetic modifiers, lithium chloride and valproic acid, further modulate these behavioural responses.
缺氧诱导因子 1(HIF-1)是检测低氧水平的关键转录因子,诱导参与介导对低氧反应的基因表达,以维持细胞的氧平衡。秀丽隐杆线虫是一种土壤线虫,它进化出了专门的化学感觉神经元,可以检测氧气水平的变化,并指导其行为和对食物的反应。然而, 基因在调节对化学缺氧的化学感觉行为中的作用尚不清楚。此外,表观遗传修饰物在介导这种对低氧的行为反应中的作用也不清楚。我们的研究解决了两个问题:(a)缺氧模拟物是否会改变蠕虫的行为?(b)这些行为是否通过 HIF 依赖性的表观遗传调节剂的表达来调节?本研究使用秀丽隐杆线虫的突变株中的已建立的行为范式,研究对化学缺氧的反应。我们表明,暴露于缺氧模拟物亚硫酸钠会改变味觉反应、趋化性、味觉可塑性和联想性条件反射行为。长期暴露于缺氧会改变野生型秀丽隐杆线虫的行为反应,这是由 HIF 通路介导的。表观遗传修饰剂,氯化锂和丙戊酸,进一步调节这些行为反应。