Regenerative Adaptation to Electrochemical Perturbation in Planaria: A Molecular Analysis of Physiological Plasticity

Summary

Anatomical homeostasis results from dynamic interactions between gene expression, physiology, and the external environment. Owing to its complexity, this cellular and organism-level phenotypic plasticity is still poorly understood. We establish planarian regeneration as a model for acquired tolerance to environments that alter endogenous physiology. Exposure to barium chloride (BaCl ₂) results in a rapid degeneration of anterior tissue in Dugesia japonica. Remarkably, continued exposure to fresh solution of BaCl ₂ results in regeneration of heads that are insensitive to BaCl ₂. RNA-seq revealed transcriptional changes in BaCl ₂-adapted heads that suggests a model of adaptation to excitotoxicity. Loss-of-function experiments confirmed several predictions: blockage of chloride and calcium channels allowed heads to survive initial BaCl ₂ exposure, inducing adaptation without prior exposure, whereas blockade of TRPM channels reversed adaptation. Such highly adaptive plasticity may represent an attractive target for biomedical strategies in a wide range of applications beyond its immediate relevance to excitotoxicity preconditioning.

Graphical Abstract

Highlights

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  Exposure to BaCl ₂ causes the heads of Dugesia japonica to degenerate

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  Prolonged exposure to BaCl ₂ results in regeneration of a BaCl ₂-insensitive head

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  Ion channel expression is altered in the head to compensate for excitotoxic stress

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  TRPMa is upregulated in BaCl ₂-treated animals; blocking TRPM prevents adaptation

Abstract

Marine Organism; Ion Activity; Cellular Physiology