Short-term hyperglycaemia induces motor defects in C. elegans.

Abstract

Hyperglycaemia causes various intracellular changes resulting in oxidative stress leading to loss of integrity and cell death. While cellular effects of hyperglycaemia have been reported extensively there is no clarity on whether the cellular changes translate into alterations in behaviour. Study of behavioural alterations also provides a sublime top-down approach to dapple the putative systems affected due to hyperglycaemic stress. Hence, this aspect of effect of hyperglycaemia deserves attention as it could be an early indicator of neurodegenerative changes. Caenorhabditis elegans is an excellent model to address these questions since it has a simple nervous system and the ability to respond to various cues.\n\nWe have investigated alteration in behaviour which involves various motor and sensory function of the C. elegans nervous system under hyperglycaemia. Exposure of C. elegans to 400 mM glucose for 4hr did not kill the worm but gave rise to decreased number of progeny, exhibiting other aberrant behaviours. This dosage was considered to cause hyperglycaemic stress and used further in the studies. Various assays that quantified behaviour, such as feeding (pharyngeal pumping/min), locomotion (distance travelled by the worms/min), olfactory response towards Butanol (response index) and gustatory response NaCl (response index) were conducted under both normal and hyperglycaemic conditions. The behavioural alterations were validated by scrutinizing changes in level of Acetylchloine which regulates motor behaviour and morphology of chemosensory neurons. Our results indicate that hyperglycaemia alters motor behaviour of the worm which was validated by a reduction in ACh levels. However, chemosensory systems were robust enough to resist reduction in neuronal integrity due to hyperglycaemic assault.