Hypoxia signalling and regulation in chemosensory behaviour of Caenorhabditis elegans

Abstract

Adaptation to hypoxia is essential to survival in most organisms; disruption of oxygen homeostasis is linked to the pathology of multiple diseases including neurodegeneration, ischaemic stroke and cancer. Hypoxia-inducible factor 1 (HIF-1) is a key transcription factor in the detection of oxygen depletion and in mediating the response to hypoxia to maintain cellular oxygen homeostasis. This study investigated hypoxia signalling in vivo using a Caenorhabditis elegans HIF-1 mutant model. The chemosensory behaviour of C. elegans was analysed through the use of chemosensory assays with a chemoattractant and a chemorepellent; the response was quantified by calculating the chemotaxis index of species. Chemosensory assays were used to analyse behavioural changes of C. elegans under oxic and hypoxic conditions and to analyse the effects of mood stabilizing drugs lithium chloride (LiCl) and valproic acid (VA). HIF-1 mutant C. elegans showed an impaired chemosensory response to a 48 h hypoxia exposure. Treatment with LiCl significantly rescued the chemosensory response of HIF-1 mutants under hypoxia, suggesting a protective effect. Treatment with VA decreased the chemosensory response of HIF-1 mutants with hypoxia exposure. Interestingly, VA also decreased the chemosensory response of wild-type species under oxic conditions, suggesting a mechanism of action independent of hypoxia.