Molecules (Feb 2025)

Young Age and Concomitant Cannabis (THC) and Ethanol (EtOH) Exposure Enhances Rat Brain Damage Through Decreased Cerebral Mitochondrial Respiration

  • Véronique Quenardelle,
  • Anne-Laure Charles,
  • Anne Charloux,
  • Jean-Sébastien Raul,
  • Valérie Wolff,
  • Bernard Geny

DOI
https://doi.org/10.3390/molecules30040918
Journal volume & issue
Vol. 30, no. 4
p. 918

Abstract

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The reason why young people taking concomitantly cannabis (THC) and ethanol (EtOH) are more prone to stroke is underresearched. To investigate whether an underlying mechanism of increased brain damage could be an impaired mitochondrial function, this experiment determined the acute effects of EtOH, both alone and associated with THC, on mitochondrial respiration and oxidative stress (hydrogen peroxide H2O2) on young (11 weeks) and middle-aged (45 weeks) brain in rats, using a high-resolution oxygraph (Oxygraph-2K, Oroboros instruments). In young brains, EtOH decreased mitochondrial respiration by −51.76 ± 2.60% (from 32.76 ± 3.82 to 17.41 ± 1.42 pmol/s/mL, p p p p p 2O2 production was similar in both age groups (1.0 ± 0.2 versus 1.1 ± 0.08 pmol O2/s/mL) and was not modified by THC addition. In conclusion, EtOH alone significantly impairs brain mitochondrial respiration and concomitant THC further aggravates such damage, particularly in young brains. These data support the hypothesis that enhanced mitochondrial dysfunction might participate in the increased occurrence of stroke in the young and urge for better prevention against EtOH and THC addictions in adolescents.

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