The Reversible Neurotoxic Effects of Methylmercury on the Dorsal Root Ganglion - Temporal Dynamics in Rats

Sep 30, 2026

Uploaded by Jacob

Methylmercury (MeHg) preferentially damages sensory neurons in the peripheral nervous system, yet the timing and reversibility of dorsal root ganglion (DRG) injury and recovery remain insufficiently defined. Wistar rats received MeHg for five consecutive days, followed by a two-day washout, repeated once, and DRG/peripheral sensory tissues were examined through 70 days. Histology, immunohistochemistry, DNA microarrays, and mercury quantification showed A-fiber density decreased at Day 14, then recovered by Day 70, while C-fibers were unchanged. DRG neuron numbers stayed stable, and DRG neuronal subtype markers (NF, TrkA, FAM19A1, TAC1, SST) declined at Day 14 and gradually returned, coinciding with a DRG mercury peak at Day 14 and normalization by Day 70, suggesting transient functional suppression without widespread neuronal loss.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

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Abstract

1. Introduction

Methylmercury poisoning and sensory-dominant impairments

Prior findings and the knowledge gap on recovery dynamics

In vivo cellular and molecular events after MeHg exposure

Article The Reversible Neurotoxic Effects of Methylmercury on the Dorsal Root Ganglion: Temporal Dynamics in Rats Yo Shinoda 1, *, Kaito Yamashiro 1, Ayaka Matsuki 1, Yuka Sekiguchi 1, Satoshi Tatsumi 1, Shino Homma-Takeda 2, Oki Sekizawa 3, Marika Abe 4,5, Misaki Ozawa 4,6, Eiko Yoshida 7,8, Yasuhiro Shinkai 9, Tsutomu Takahashi 1, Yasuyuki Fujiwara 1 and Toshiyuki Kaji 8, * Academic Editor: Graz˙yna Gromadzka Received: 4 November 2025 Revised: 10 December 2025 Accepted: 16 December 2025 Published: 22 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji 192-0392, Tokyo, Japan; [kitymsr@toyaku.ac.jp](kitymsr@toyaku.ac.jp) (K.Y.); [tsutomu@toyaku.ac.jp](tsutomu@toyaku.ac.jp) (T.T.); [yasuyuki@toyaku.ac.jp](yasuyuki@toyaku.ac.jp) (Y.F.) 2 Institute for Radiological Science, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage, Chiba 263-8555, Chiba, Japan; [takeda.shino@qst.go.jp](takeda.shino@qst.go.jp) 3 Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo 679-5198, Hyogo, Japan; [sekizawa@spring8.or.jp](sekizawa@spring8.or.jp) 4 Global Science Campus, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi 332-0012, Saitama, Japan 5 Shibuya Junior & Senior High School, Shibuya Kyoiku Gakuen, 1-21-18 Shibuya, Shibuya 150-0002, Tokyo, Japan 6 Hiroo Gakuen Senior High School, 5-1-14 Minamiazabu, Minato 106-0047, Tokyo, Japan 7 Sustainable System Research Laboratory, Central Research Institute of Electric Power Industry, 1646 Abiko, Abiko 270-1194, Chiba, Japan; [yoshida3881@criepi.denken.or.jp](yoshida3881@criepi.denken.or.jp) 8 Faculty of Pharmaceutical Sciences, Tokyo University of Science, 6-3-1 Niijuku, Katsushika 125-8585, Tokyo, Japan 9 Environmental Biology Laboratory, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji 192-0392, Tokyo, Japan; [yshinkai@toyaku.ac.jp](yshinkai@toyaku.ac.jp) * Correspondence: [shinoda@toyaku.ac.jp](shinoda@toyaku.ac.jp) (Y.S.); [t-kaji@rs.tus.ac.jp](t-kaji@rs.tus.ac.jp) (T.K.) 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-do

FAQs

Did MeHg cause widespread neuron loss in the DRG?

The total number of DRG neurons remained stable, and subtype marker-selected neuronal populations decreased at Day 14 then gradually recovered, indicating a reversible suppression rather than widespread neuronal loss.

Sep 30, 2026

Uploaded by Jacob