Sensory neuron dysfunction and hyperexcitability in dorsal root ganglia at disease onset in the SOD1G93A mouse model of ALS.
- 1Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, The University of Osaka, Suita, Japan
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder traditionally characterized by motor neuron degeneration, but emerging evidence indicates sensory system involvement. Despite reports of sensory abnormalities in some patients, the molecular and functional alterations in dorsal root ganglion (DRG) neurons remain insufficiently characterized. We investigated DRG pathology at disease onset in 12-week-old SOD1G93A mice using an integrated transcriptomic, morphological, and electrophysiological approach. RNA sequencing of lumbar DRG identified 35 differentially expressed genes, predominantly upregulated, enriched in oxidative stress-related and phagosome pathways. Comparative analysis with motor neuron transcriptomes revealed distinct gene expression profiles, indicating sensory neuron-specific molecular responses. Immunohistochemistry demonstrated reduced soma diameter in both A- and C-fiber DRG neurons. Nav channel colocalization increased for Nav1.7 in A fibers and Nav1.8 in both fiber types, whereas Nav1.6 was unchanged. Whole-cell patch-clamp recordings showed depolarized resting membrane potential, increased spike amplitude, and enhanced repetitive firing in A-fiber neurons, consistent with hyperexcitability, while C fibers showed no significant functional changes. These findings demonstrate early molecular, structural, and functional alterations in primary sensory neurons in ALS, supporting pathology beyond motor neurons and identifying sensory neuron excitability as a potential therapeutic target.
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BibTeX
@misc{nishiura2026sensory,
title = {{Sensory neuron dysfunction and hyperexcitability in dorsal root ganglia at disease onset in the SOD1G93A mouse model of ALS.}},
author = {A. Nishiura and S. Seki and T. Kobayashi and Y. Kitaoka and S. Kawata and T. Yamamoto and K. Miyagawa and T. Uchihashi and Y. Ohtake and T. Itokazu and T. Yamashita and M. Ono and Y. Yokota and E. T. Isomura and S. Tanaka},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.27.747263},
url = {https://www.biorxiv.org/content/10.64898/2026.08.27.747263v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Sensory neuron dysfunction and hyperexcitability in dorsal root ganglia at disease onset in the SOD1G93A mouse model of ALS.
AU - A. Nishiura
AU - S. Seki
AU - T. Kobayashi
AU - Y. Kitaoka
AU - S. Kawata
AU - T. Yamamoto
AU - K. Miyagawa
AU - T. Uchihashi
AU - Y. Ohtake
AU - T. Itokazu
AU - T. Yamashita
AU - M. Ono
AU - Y. Yokota
AU - E. T. Isomura
AU - S. Tanaka
PY - 2026
DA - 2026/08/27
PB - bioRxiv
DO - 10.64898/2026.08.27.747263
UR - https://www.biorxiv.org/content/10.64898/2026.08.27.747263v1
AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder traditionally characterized by motor neuron degeneration, but emerging evidence indicates sensory system involvement. Despite reports of sensory abnormalities in some patients, the molecular and functional alterations in dorsal root ganglion (DRG) neurons remain insufficiently characterized. We investigated DRG pathology at disease onset in 12-week-old SOD1G93A mice using an integrated transcriptomic, morphological, and electrophysiological approach. RNA sequencing of lumbar DRG identified 35 differentially expressed genes, predominantly upregulated, enriched in oxidative stress-related and phagosome pathways. Comparative analysis with motor neuron transcriptomes revealed distinct gene expression profiles, indicating sensory neuron-specific molecular responses. Immunohistochemistry demonstrated reduced soma diameter in both A- and C-fiber DRG neurons. Nav channel colocalization increased for Nav1.7 in A fibers and Nav1.8 in both fiber types, whereas Nav1.6 was unchanged. Whole-cell patch-clamp recordings showed depolarized resting membrane potential, increased spike amplitude, and enhanced repetitive firing in A-fiber neurons, consistent with hyperexcitability, while C fibers showed no significant functional changes. These findings demonstrate early molecular, structural, and functional alterations in primary sensory neurons in ALS, supporting pathology beyond motor neurons and identifying sensory neuron excitability as a potential therapeutic target.
ER -