Performance changes and neuromuscular alterations in sprague dawley rats following repeated occupational exposures to the pesticide malathion
4 affiliations
- 1Naval Medical Research Unit Dayton, Environmental Health Effects Laboratory, Wright-Patterson Air Force Base, Dayton, Ohio, United States of America
- 2Wright State University, Dayton, Ohio, United States of America
- 3Leidos, Reston, Virginia, United States of America
- 4Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, United States of America
Abstract
Organophosphate pesticides, such as malathion, have been linked to various pathological effects, including neurodegeneration. Acute exposure to malathion, a non-reversible acetylcholinesterase (AChE) inhibitor, causes adverse effects in mammals. However, the impact of subacute, occupational-like repeated exposure on motoneuron (MN) and neuromuscular junction (NMJ) anatomy is less understood. We hypothesized that repeated malathion exposure would produce motor performance deficits accompanied by anatomical alterations in spinal MNs and NMJs consistent with neurodegeneration. We also hypothesized that galantamine, a reversible AChE inhibitor, would provide neuroprotection. Adult male and female Sprague–Dawley rats received subcutaneous saline, malathion (50 mg/kg), galantamine (5.0 mg/kg), or both once daily, five days per week for four weeks. Animals were evaluated immediately after the final exposure and following a four-week recovery period. After exposure, no evidence of spinal astrogliosis and plasma cholinesterase activity was detected. Despite this, cholinergic (C-bouton) synaptic remodeling was observed on lumbar spinal MN somas in females and both sexes showed decreased open-field motor activity. Exposed males performed worse on the accelerod, while exposed females exhibited reduced grip strength. These functional deficits corresponded with a 25% decrease in hindlimb NMJ innervation in both sexes. After recovery, exposed rats showed increased NMJ fragmentation, suggesting remodeling during recovery. Galantamine treatment protected against health effects associated with repeated occupational-like malathion exposure, indicating involvement of cholinergic mechanisms despite minimal changes in plasma cholinesterase activity. Overall, repeated low-concentration malathion exposure is associated with locomotor deficits and peripheral neuropathy.
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BibTeX
@article{miller2026performance,
title = {{Performance changes and neuromuscular alterations in sprague dawley rats following repeated occupational exposures to the pesticide malathion}},
author = {Kaitlyn M. Miller and Dakota R. McMeans and Martha J. Sonner and David R. Ladle and Shannon H. Romer},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0357900},
url = {https://doi.org/10.1371/journal.pone.0357900},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Performance changes and neuromuscular alterations in sprague dawley rats following repeated occupational exposures to the pesticide malathion
AU - Kaitlyn M. Miller
AU - Dakota R. McMeans
AU - Martha J. Sonner
AU - David R. Ladle
AU - Shannon H. Romer
PY - 2026
DA - 2026/09/15
JO - PLOS One
DO - 10.1371/journal.pone.0357900
UR - https://doi.org/10.1371/journal.pone.0357900
AB - Organophosphate pesticides, such as malathion, have been linked to various pathological effects, including neurodegeneration. Acute exposure to malathion, a non-reversible acetylcholinesterase (AChE) inhibitor, causes adverse effects in mammals. However, the impact of subacute, occupational-like repeated exposure on motoneuron (MN) and neuromuscular junction (NMJ) anatomy is less understood. We hypothesized that repeated malathion exposure would produce motor performance deficits accompanied by anatomical alterations in spinal MNs and NMJs consistent with neurodegeneration. We also hypothesized that galantamine, a reversible AChE inhibitor, would provide neuroprotection. Adult male and female Sprague–Dawley rats received subcutaneous saline, malathion (50 mg/kg), galantamine (5.0 mg/kg), or both once daily, five days per week for four weeks. Animals were evaluated immediately after the final exposure and following a four-week recovery period. After exposure, no evidence of spinal astrogliosis and plasma cholinesterase activity was detected. Despite this, cholinergic (C-bouton) synaptic remodeling was observed on lumbar spinal MN somas in females and both sexes showed decreased open-field motor activity. Exposed males performed worse on the accelerod, while exposed females exhibited reduced grip strength. These functional deficits corresponded with a 25% decrease in hindlimb NMJ innervation in both sexes. After recovery, exposed rats showed increased NMJ fragmentation, suggesting remodeling during recovery. Galantamine treatment protected against health effects associated with repeated occupational-like malathion exposure, indicating involvement of cholinergic mechanisms despite minimal changes in plasma cholinesterase activity. Overall, repeated low-concentration malathion exposure is associated with locomotor deficits and peripheral neuropathy.
SN - 1932-6203
ER -