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The Carbamate, Physostigmine does not Impair Axonal Transport in Rat Cortical Neurons
Journal article   Open access   Peer reviewed

The Carbamate, Physostigmine does not Impair Axonal Transport in Rat Cortical Neurons

Sean X Naughton, Wayne D Beck, Zhe Wei, Guangyu Wu, Peter W Baas and Alvin V Terry
Neuroscience insights, v 16, pp 263310552110202-26331055211020289
24 May 2021
DOI: https://doi.org/10.1177/26331055211020289
PMID: 34104889
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1177/26331055211020289View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

agriculture carbamate gulf war illness Gulf War Illness (GWI) and Nervous System Disorders insecticide organophosphate Pesticide
Among the various chemicals that are commonly used as pesticides, organophosphates (OPs), and to a lesser extent, carbamates, are most frequently associated with adverse long-term neurological consequences. OPs and the carbamate, pyridostigmine, used as a prophylactic drug against potential nerve agent attacks, have also been implicated in Gulf War Illness (GWI), which is often characterized by chronic neurological symptoms. While most OP- and carbamate-based pesticides, and pyridostigmine are relatively potent acetylcholinesterase inhibitors (AChEIs), this toxicological mechanism is inadequate to explain their long-term health effects, especially when no signs of acute cholinergic toxicity are exhibited. Our previous work suggests that a potential mechanism of the long-term neurological deficits associated with OPs is impairment of axonal transport (AXT); however, we had not previously evaluated carbamates for this effect. Here we thus evaluated the carbamate, physostigmine (PHY), a highly potent AChEI, on AXT using an in vitro neuronal live imaging assay that we have previously found to be very sensitive to OP-related deficits in AXT. We first evaluated the OP, diisopropylfluorophosphate (DFP) (concentration range 0.001-10.0 µM) as a reference compound that we found previously to impair AXT and subsequently evaluated PHY (concentration range 0.01-100 nM). As expected, DFP impaired AXT in a concentration-dependent manner, replicating our previously published results. In contrast, none of the concentrations of PHY (including concentrations well above the threshold for impairing AChE) impaired AXT. These data suggest that the long-term neurological deficits associated with some carbamates are not likely due to acute impairments of AXT.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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