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Introduction <p>Manganism is a disease characterized by the degeneration of dopamine neurons and shares distinct similarities with Parkinson’s Disease (PD). One of the environmental risk factors for PD is exposure to manganese (Mn). However, the precise role of dopamine (DA) in Mn-mediated neurodegeneration, as well as its developmental effects, has not been well studied.</p> Materials and methods <p>To understand the mechanisms involved in Mn-induced neurotoxicity, we used <i>C. elegans</i> as a genetic and behavioral model system to assess dopaminergic neurodegeneration, survival, and locomotor function following MnCl<sub>2</sub> and dopamine exposure.</p> Results <p>Our results showed that adult worms treated with 50 and 100 mM MnCl<sub>2</sub> have significantly increased DA neurodegeneration. Interestingly L1 larvae did not show neurodegeneration when treated with MnCl<sub>2</sub> alone but showed a significant increase in neurodegeneration (50%) when MnCl<sub>2</sub> exposure was given after DA pretreatment. However, both adult and larval exposure to MnCl<sub>2</sub> demonstrated significant toxicity by reducing the survival rate. In adult worms, treatment with 100 mM MnCl<sub>2</sub> after DA pretreatment led to a greater percentage of neurodegeneration. Adult worms exposed to Mn or DA alone showed recovery of neuronal dopamine function within 24&#xa0;h; however, those exposed to both exogenous DA and Mn showed prolonged behavioural defects. The <i>cat-2</i> mutants, which lack DA, were resistant to Mn-mediated neurodegeneration. In contrast, <i>cat-2</i> overexpressing strain displayed severe neurodegeneration at lower concentrations of MnCl<sub>2</sub> (50&#xa0;mM).</p> Conclusion <p>Our results on biochemical, behavioural and genetic assays confirmed that both endogenous and exogenous DA plays a crucial role in determining the sensitivity to Mn-induced dopaminergic neurotoxicity.</p>

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Dopamine controls the sensitivity to manganese induced dopaminergic neurotoxicity in Caenorhabditis elegans

  • 期刊论文

  • 发表日期：

    2026年4月10日

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  • Vishnu Raj,
  • Anoopkumar Thekkuveettil

摘要

Introduction

Manganism is a disease characterized by the degeneration of dopamine neurons and shares distinct similarities with Parkinson’s Disease (PD). One of the environmental risk factors for PD is exposure to manganese (Mn). However, the precise role of dopamine (DA) in Mn-mediated neurodegeneration, as well as its developmental effects, has not been well studied.

Materials and methods

To understand the mechanisms involved in Mn-induced neurotoxicity, we used C. elegans as a genetic and behavioral model system to assess dopaminergic neurodegeneration, survival, and locomotor function following MnCl2 and dopamine exposure.

Results

Our results showed that adult worms treated with 50 and 100 mM MnCl2 have significantly increased DA neurodegeneration. Interestingly L1 larvae did not show neurodegeneration when treated with MnCl2 alone but showed a significant increase in neurodegeneration (50%) when MnCl2 exposure was given after DA pretreatment. However, both adult and larval exposure to MnCl2 demonstrated significant toxicity by reducing the survival rate. In adult worms, treatment with 100 mM MnCl2 after DA pretreatment led to a greater percentage of neurodegeneration. Adult worms exposed to Mn or DA alone showed recovery of neuronal dopamine function within 24 h; however, those exposed to both exogenous DA and Mn showed prolonged behavioural defects. The cat-2 mutants, which lack DA, were resistant to Mn-mediated neurodegeneration. In contrast, cat-2 overexpressing strain displayed severe neurodegeneration at lower concentrations of MnCl2 (50 mM).

Conclusion

Our results on biochemical, behavioural and genetic assays confirmed that both endogenous and exogenous DA plays a crucial role in determining the sensitivity to Mn-induced dopaminergic neurotoxicity.