Abstract
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.
Highlights
The effect of acetylcholinesterase inhibitors aldicarb and neostigmine on sinusoidal locomotion of the soil nematode Caenorhabditis elegans induced by mechanical stimulus was experimentally studied
Short-term (15 min) exposure to aldicarb (10–40 μM) or neostigmine (4–12 mM) caused dose-dependent dysfunction of C. elegans locomotion in all nematodes but without a complete loss of motor activity. These results indicate that partial acetylcholinesterase inhibition in C. elegans disturbs the muscle contraction-relaxation balance necessary for sinusoidal body movements during locomotion, but cholinergic synaptic transmission in neuro-muscular junctions is retained
A known fact is that octopamine and dopamine in C. elegans organism have not direct effect on locomotor muscles, and their influence on behavioral sensitivity to aldicarb may be a consequence of the modulation of transneuronal synapses rather than neuromuscular junctions
Summary
Проведено экспериментальное исследование влияния ингибиторов ацетилхолинэстеразы алдикарба и неостигмина на синусоидальные локомоторные движения почвенной нематоды Caenorhabditis elegans, индуцированные механическим стимулом. Результаты работы показывают, что самой чувствительной мишенью токсического действия эндогенного ацетилхолина при превышении его оптимального уровня в организме C. elegans является нервная система. Универсальным механизмом токсического действия ингибиторов ацетилхолинэстеразы на организмы человека и животных является аномальное повышение концентрации эндогенного ацетилхолина, которое нарушает поведение, физиологическое состояние организма и может вызывать его гибель [Sikora, Hartwig, 1991; Baron, 1994; Assis et al, 2012; Tayeb et al, 2012; Čolović et al, 2013; Silva et al, 2013; Metcalf, Horowitz, 2014]. Для проверки этой гипотезы проведены эксперименты, в которых исследовалось токсическое действие ингибиторов ацетилхолинэстеразы на поведение свободноживущей почвенной нематоды Caenorhabditis elegans
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