It is known that the first ethanol metabolite acetaldehyde (AA) is the mediator and modulator of ethanol actions in the human brain. Basic enzymes of ethanol metabolism, such as alcoholdehydrogenase and aldehyde dehydrogenase (ALDH) are very conservative in evolution. Therefore it is possible that AA plays an important role in ethanol effects upon the simple nervous systems of invertebrates.
Results of our experiments revealed AA involvement in the tolerance to ethanol of simple nervous system of C. elegans (wild type strain N2): (i) Elevation of AA concentration during ethanol metabolism by inhibition of ALDH (preliminary 16-hours exposition of worms on agar plates containing selective inhibitor of ALDH disulfiram (antabus) in concentration 0.8 mg/ml and seeded with E. coli OP50) protected worms’ behavior against disturbances induced by ethanol. These disturbances revealed in numerous reversible incoordinations of swimming induced by mechanical stimulus in experiments with worms incubated singly in liquid medium with ethanol (1-3%); (ii) Low concentrations of exogenous AA (30–75 µg/ml) mimics protective effect of disulfiram in the ethanol containing medium.
It is known that AA mediates many unfavorable effects of alcohol in human nervous system. However our data indicate that AA can’t be the mediator of negative effect of ethanol upon C. elegans swimming: (i) Exogenous AA (75–300 µg/ml) induces very specific form of behavior disturbance similar to kinked motion and coiled posture of unc-1 and unc-8 mutants (Park, Horvitz, 1986; Hecht et al., 1996), and this form of behavior disturbance was not revealed among swimming disturbances induced by ethanol; (ii) Disulfiram sensitizes human organism to adverse ethanol action but has opposite protective effect on C.elegans locomotion in the medium containing alcohol; (iii) Low concentrations of AA protect C.elegans locomotion against unfavorable ethanol effect; (iv) Low concentrations of ethanol (0.5-1.0 %) prevent worms’ kinking and coiling induced by AA.
In general our data suggest cross modulation of unfavorable effects of ethanol and its first metabolite upon C. elegans behavior. This cross modulation can be adaptive for C. elegans since in all known natural habitats of this nematode (compost soils) constantly or periodically there are conditions for fermentation, such as substrates for fermentation and oxygen deficit resulting from metabolism of aerobic microorganisms, and ethanol and other alcohols are volatile chemoattractants for C. elegans.
Park ECh and Horvitz HR. (1986). Mutations with dominant effects on the behavior and morphology of the nematode Caenorhabditis elegans. Genetics. 113, 821–852.
Hecht RM, Norman MA, Vu T. and Jones W. (1996). A novel set of uncoordinated mutants in Caenorhabditis elegans by cold-sensitive mutations. Genome. 39, 459-464.
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