Performance changes and neuromuscular alterations in sprague dawley rats following repeated occupational exposures to the pesticide malathion

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.