Cisplatin-triggered sensory dysfunction in NER-defective C. elegans involves GABAergic and cholinergic signaling

Cisplatin reduces GABA levels and disrupts GABAergic neuron integrity in NER-defective Caenorhabditis elegans, and GABA supplementation rescues ercc-1 mutants’ sensory dysfunction.

• Why it matters: DNA damage from cisplatin contributes to neurotoxicity, but the neurotransmission mechanisms linking DNA repair defects to sensory impairment are unclear.
• What they did: Using the nucleotide excision repair–deficient ercc-1 mutant, the authors measured cisplatin effects on chemotaxis, GABA levels, GABAergic neuron morphology, and transcriptomes, and tested GABA supplementation and the cholinergic agonist carbachol.
• The result: Cisplatin triggers broad transcriptional changes, including acetylcholine-mediated neurotransmission pathways, and in ercc-1 mutants carbachol worsens sensory dysfunction while GABA substitution reverses cisplatin-evoked neurotoxicity.

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