А.В. Егорова, Т.Б. Калинникова, Д.М. Хакимова, Р.Р. Шагидуллин.
Нейротоксическое действие ингибиторов ацетилхолинэстеразы на организм почвенной нематоды Caenorhabditis elegans Maupas
Keywords: Caenorhabditis elegans; acetylcholinesterase inhibitors; aldicarb; neostigmine; dopamine; octopamine
The investigation of the influence of acetylcholinesterase inhibitors aldicarb and neostigmine on soil nematode Caenorhabditis elegans swimming as induced by mechanical stimulus was performed. Short-term (30 minutes) to aldicarb (10–40 µM) or neostigmine (4–8 mM) caused disturbances of C. elegans motor program of swimming in dose-dependent manner by the retention of swimming ability of all nematodes. These results indicate that partial acetylcholinesterase inhibition in C. elegans organism disturbs the balance of muscle excitation and inhibition necessary for sinusoidal body movements during swimming, but cholinergic synaptic transmission in neuro-muscular junctions is retained. Octopamine and dopamine increased the sensitivity of C. elegans behavior to toxic aldicarb action. Octopamine and dopamine in C. elegans organism don't influence directly on locomotor muscles. Therefore their influence on behavior sensitivity to aldicarb may be a consequence of modulation of neuron-neuron synapses, but not neuromuscular junctions by octopamine and dopamine. Disturbances of motor program of C. elegans swimming revealed in this work are the consequence of anomalous rise of acetylcholine level in the nervous system, but not in neuromuscular junctions. The most likely mechanism of disturbances of functions of C. elegans nervous system by partial acetylcholinesterase inhibition is hyperactivation of neuronal nicotinic cholinoreceptors. Results of this work show that reasons of toxic action of anomalous high acetylcholine level are highly conservative in evolution, and the most sensitive target of exceeding of optimal level of endogenous acetylcholine not only in human organisms, organisms of vertebrates and higher invertebrates, but also in simple organisms of nematodes is the nervous system.
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