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The Reversible Neurotoxic Effects of Methylmercury on the Dorsal Root Ganglion: Temporal Dynamics in Rats
Yo Shinoda1, Kaito Yamashiro1, Ayaka Matsuki1
1Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji 192-0392, Tokyo, Japan.
Abstract:
Methylmercury (MeHg) is a well-known environmental neurotoxicant that preferentially affects sensory neurons in the peripheral nervous system. While sensory-dominant neuropathy has long been described in Minamata disease, the temporal dynamics of dorsal root ganglion (DRG) injury and recovery remain incompletely understood. In this study, Wistar rats were exposed to MeHg for five consecutive days, followed by a two-day treatment-free period; this regimen was repeated once. The DRG and peripheral sensory fibers were analyzed up to 70 days after exposure. Histological and immunohistochemical analyses, DNA microarrays, and mercury quantification and distribution mapping were performed. The A-fiber density was significantly reduced at Day 14 but recovered by Day 70, whereas C-fibers showed no significant change. The total number of DRG neurons remained stable. Immunohistochemical analyses demonstrated that subtype marker-selected neurons (NF, TrkA, FAM19A1, TAC1, SST) decreased at Day 14 and gradually recovered thereafter. DNA microarray analysis at Day 14 revealed a broad downregulation of DRG neuronal subtype marker genes. The mercury concentration in the DRG peaked at Day 14 and declined to the control level by Day 70, with in situ imaging confirming preferential accumulation in DRG neurons. These data suggest that the short-term MeHg exposure caused a transient functional suppression of DRG neurons without widespread neuronal loss. The selective and reversible downregulation of neuronal phenotypes, coupled with preferential Hg accumulation in DRG neurons, underlies the sensory-dominant and potentially reversible features of MeHg neurotoxicity.
Insights
Short-term methylmercury (MeHg) exposure transiently suppressed sensory neurons in the dorsal root ganglion (DRG) without causing widespread cell death. Nerve fiber density and neuron markers recovered within 70 days, indicating potential reversibility of MeHg neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Environmental Health
Background:
- Methylmercury (MeHg) is a potent environmental neurotoxicant.
- MeHg preferentially impacts peripheral sensory neurons, a hallmark of Minamata disease.
- The precise timing of dorsal root ganglion (DRG) injury and recovery from MeHg exposure is not fully understood.
Purpose of the Study:
- To investigate the temporal effects of short-term methylmercury exposure on DRG neurons and sensory fibers.
- To understand the mechanisms underlying sensory-dominant neurotoxicity and its potential reversibility.
Main Methods:
- Wistar rats were exposed to MeHg over a short period, with analyses conducted up to 70 days post-exposure.
- Histological, immunohistochemical, and DNA microarray analyses were performed.
- Mercury levels and distribution in the DRG were quantified using advanced imaging techniques.
Main Results:
- A-fiber density decreased by Day 14 but recovered by Day 70; C-fibers remained unchanged.
- DRG neuronal subtype markers decreased at Day 14 and gradually recovered.
- Mercury concentration in the DRG peaked at Day 14 and returned to control levels by Day 70, with preferential accumulation in DRG neurons.
Conclusions:
- Short-term MeHg exposure induces transient functional suppression of DRG neurons, not widespread neuronal loss.
- The observed neurotoxicity is characterized by selective, reversible downregulation of neuronal phenotypes.
- Preferential mercury accumulation in DRG neurons contributes to the sensory-dominant and potentially reversible nature of MeHg neurotoxicity.
