Browsing by Subject "yleisanesteetit"
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(2024)General anaesthetics are pharmaceutical agents used to induce general anaesthesia, a reversible state of unconsciousness. Caenorhabditis elegans, a nematode species, has been successfully used as a model organism in the study of gaseous anaesthetics due to its amenability to genetic modification, fully mapped nervous system connectome and high evolutionary conservation. However, C. elegans is less well characterised as a model organism in the study of non-gaseous anaesthetics. The primary aim of the study was to study the potential of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and urethane, a nonselective modulator of various neurotransmitter-gated ion channels, to immobilise C. elegans without activating antioxidant response signalling by transcription factor SKN-1, the nematode orthologue of the mammalian Nrf/CNC proteins. The transparent body of C. elegans enables microscopic imaging of cellular processes, but high-quality imaging requires the immobilisation of the worm. A commonly used chemical immobilising agent, sodium azide, causes SKN-1 activation in C. elegans, which may limit the use of sodium azide in studies on SKN-1 promoters. A secondary aim of this study was to study the impact of ketamine, an activator of mTOR (mechanistic target of rapamycin) signalling, on the lifespan of C. elegans. The lifespan of C. elegans has been found to increase with inhibition of the mTOR homologue pathway in previous studies. Ketamine and urethane were administered to wild-type C. elegans in aqueous media in 96-well plates. Behavioural endpoints of immobility and uncoordination were assessed manually via microscopic observation and video recordings. SKN-1 activation was studied by measuring drug-induced fluorescence in mutant strain CL2166, which carries a green fluorescent protein reporter of SKN-1 downstream target GST-4 (glutathione-S-transferase). A lifespan assay was performed with sterile C. elegans strain SS104 by incorporating ketamine in the worm maintenance agar. In this study, urethane did not appear to be a potent immobilisation agent. Ketamine was found to cause reversible weak immobilisation at a similar concentration at which sodium azide fully paralyses wild-type C. elegans. At lower doses ketamine caused uncoordinated locomotion. Short-term exposure to an immobility-inducing dose of ketamine was not found to significantly activate SKN-1. In the lifespan assay, ketamine unexpectedly appeared to significantly increase the nematode lifespan compared to control treatment.
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