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Published on: May 20, 2020
Methylmercury-induced hair cell loss requires hydrogen peroxide production and leukocytes in zebrafish embryos
Zidie Luo1, Shaojuan Guo1, Nga Yu Ho2
1State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, 100012, Beijing, China.
Abstract:
Hearing impairment and deafness is frequently observed as one of the neurological signs in patients with Minamata disease caused by methylmercury (MeHg) poisoning. Loss of hair cells in humans and animals is a consequence of MeHg poisoning. However, it is still not clear how MeHg causes hearing deficits. We employed the hair cells of the lateral line system of zebrafish embryos as a model to explore this question. We exposed transgenic zebrafish embryos to MeHg (30-360 μg/L) at the different stages, and scored the numbers of hair cells. We find that MeHg-induced reduction of hair cells is in a concentration dependent manner. By employing antisense morpholino against to pu.1, we confirm that loss of hair cells involves the action of leukocytes. Moreover, hair cell loss is attenuated by co-treating MeHg-exposed embryos with pharmacological inhibitors of NADPH oxidases named diphenyleneiodonium (DPI) and VAS2870. In situ gene expression analysis showed that genes encoding the SQSTM1-Keap1-Nrf2 systems involved in combating oxidative stress and immune responses are highly expressed in the lateral line organs of embryos exposed to MeHg. This suggests that induction of hydrogen peroxide (H2O2) is the primary effect of MeHg on the hair cells. Genes induced by MeHg are also involved in regeneration of the hair cells. These features are likely related to the capacity of the zebrafish to regenerate the lost hair cells.
Insights
Methylmercury (MeHg) poisoning causes hair cell loss and hearing deficits by inducing oxidative stress and leukocyte action. Zebrafish hair cells show regeneration potential, offering insights into MeHg
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Methylmercury (MeHg) poisoning is linked to neurological deficits, including hearing impairment and hair cell loss.
- The precise mechanisms by which MeHg induces hearing deficits remain unclear.
- Hair cell damage is a known consequence of MeHg exposure in various organisms.
Purpose of the Study:
- To investigate the mechanisms underlying methylmercury-induced hair cell loss using zebrafish embryos.
- To explore the role of leukocytes and oxidative stress in MeHg-induced ototoxicity.
- To examine the potential for hair cell regeneration in response to MeHg exposure.
Main Methods:
- Exposure of transgenic zebrafish embryos to varying concentrations of methylmercury (MeHg).
- Quantification of hair cell numbers in the lateral line system.
- Utilizing antisense morpholino against pu.1 to assess leukocyte involvement.
- Employing NADPH oxidase inhibitors (DPI, VAS2870) to evaluate the role of oxidative stress.
- In situ gene expression analysis to identify molecular pathways involved.
Main Results:
- MeHg exposure caused a concentration-dependent reduction in hair cell numbers.
- Leukocyte activity was confirmed to be involved in MeHg-induced hair cell loss.
- Inhibition of NADPH oxidases attenuated MeHg-induced hair cell loss.
- Genes associated with oxidative stress (SQSTM1-Keap1-Nrf2 system) and immune responses were upregulated.
- Upregulated genes also indicated involvement in hair cell regeneration.
Conclusions:
- Methylmercury induces hair cell loss primarily through oxidative stress (hydrogen peroxide) and leukocyte action.
- Zebrafish possess a capacity for hair cell regeneration following MeHg-induced damage.
- The zebrafish lateral line system serves as a valuable model for studying MeHg ototoxicity and regeneration mechanisms.
