‘Acrylamide-induced’ neuropathy and impairment of axonal transport of proteins. I. Multifocal retention of fast transported proteins at the periphery of axons as revealed by light microscope radioautography

Souyri, F.; Chrétien, M; Droz, Bernard

doi:10.1016/0006-8993(81)90715-0

Cited by 40 publications

(10 citation statements)

References 14 publications

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“…Additional studies documented accumulations of tubulovesicular profiles within axons prior to degeneration (Abou-Donia and Lapadula, 1990), a pathology that is consistent with stagnation of membrane traffic (Chretien et al, 1981; Souyri et al, 1981). More recent work in our laboratories indicated that repeated exposures to OPs at doses that were not associated with acute signs of toxicity can lead to deficits in axonal transport.…”

Section: Op Targets Other Than Cholinesterasementioning

confidence: 87%

Functional consequences of repeated organophosphate exposure: Potential non-cholinergic mechanisms

Terry

2012

Pharmacology & Therapeutics

214

164

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The class of chemicals known as the “organophosphates” (OPs) comprises many of the most common agricultural and commercial pesticides that are used worldwide as well as the highly toxic chemical warfare agents. The mechanism of the acute toxicity of OPs in both target and non-target organisms is primarily attributed to inhibitory actions on various forms of cholinesterase leading to excessive peripheral and central cholinergic activity. However, there is now substantial evidence that this canonical (cholinesterase-based) mechanism cannot alone account for the wide-variety of adverse consequences of OP exposure that have been described, especially those associated with repeated exposures to levels that produce no overt signs of acute toxicity. This type of exposure has been associated with prolonged impairments in attention, memory, and other domains of cognition, as well as chronic illnesses where these symptoms are manifested (e.g., Gulf War Illness, Alzheimer’s disease). Due to their highly reactive nature, it is not surprising that OPs might alter the function of a number of enzymes and proteins (in addition to cholinesterase). However, the wide variety of long-term neuropsychiatric symptoms that have been associated with OPs suggests that some basic or fundamental neuronal process was adversely affected during the exposure period. The purpose of this review is to discuss several non-cholinesterase targets of OPs that might affect such fundamental processes and includes cytoskeletal and motor proteins involved in axonal transport, neurotrophins and their receptors, and mitochondria (especially their morphology and movement in axons). Potential therapeutic implications of these OP interactions are also discussed.

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Section: Op Targets Other Than Cholinesterasementioning

confidence: 87%

Functional consequences of repeated organophosphate exposure: Potential non-cholinergic mechanisms

Terry

2012

Pharmacology & Therapeutics

214

164

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“…OPs that produce delayed neurotoxicity (at high doses) cause accumulations of tubulovesicular profiles within axons prior to degeneration (Abou-Donia and Lapadula, 1990), a pathology that is consistent with the stagnation of membrane traffic Souyri et al, 1981). In one study, fast anterograde AXT was reduced by phenylphosphonothioate esters and trio-cresyl phosphate but not by the non-neurotoxic agent parathion (Reichart and Abou-Donia, 1980).…”

mentioning

confidence: 94%

Repeated Exposures to Subthreshold Doses of Chlorpyrifos in Rats: Hippocampal Damage, Impaired Axonal Transport, and Deficits in Spatial Learning

Terry¹,

Stone²,

Buccafusco³

et al. 2003

J Pharmacol Exp Ther

100

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Organophosphorus (OP) compounds are detectable in the environment for years after use and endanger many populations. Although the effects of acutely toxic doses of many OP compounds are well described, much less is known about repeated low-level exposures. The purpose of these studies was to further evaluate potential toxicological effects of the extensively used OP pesticide chlorpyrifos (CPF) in rats. CPF, across a range of subthreshold doses (i.e., for acute toxicity), reduced rearing and sniffing activity and the magnitude of weight gain over 14 days of repeated exposure. Performance in a spatial learning task was impaired after 14 days of exposure to CPF (18.0 and 25.0 mg/kg) when testing was initiated 24 h after the last injection but not after a 14-day washout. However, inhibition of both fast anterograde and retrograde axonal transport was observed for up to 20 days after exposure to 25.0 mg/kg CPF. Studies using hippocampal cultures indicated that 8 days of continuous exposure to the parent compound, CPF (Ն100 M), resulted in cell toxicity and death. Furthermore, a dose (2.5 mg/kg) of CPF that had no effects on weight gain or memory performance when administered 5 days per week over 38 days impaired forelimb grip strength in the later days of testing. Collectively, these results indicate that repeated exposures to subthreshold doses of CPF may lead to growth retardation, behavioral abnormalities, and muscle weakness. Some of these symptoms may be attributed to effects of the OP on axonal transport.

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“…The increase in the A12 nerve content and the reduction in its flow rate could allow, for example, a quantification of the primary defects observed in acrylamide poisoning, that is, the focal accumulations of fast-transported proteins in the SER and resulting reduction in the amount of these components arriving at nerve endings. 40 In addition, it may be inferred from our present data, which show no impairment of fast retrograde transport, that acrylamide would not affect the fast transport mechanism itself, but rather, the dispatching to presynaptic structures of fast anterogradely transported proteins. This defect was also suspected by other authors16,22 to be responsible for the preferential impairment of nerve terminals in acrylamide-intoxicated animals.…”

Section: Dlscusslonmentioning

confidence: 47%

“…Histological sections of distal branches of the sciatic nerve (digital nerve) showed that after 12 acrylamide injections most of the nerve fibers displayed degenerating axons and myelin ovoids. 40 However, at the level of the thigh, that is, in the proximal region where axonal transport of AChE was tested, most of the axons were normal, although very few were observed displaying local swellings with accumulation of densely stained materiaL40 Leg muscles. After 12 injections of acrylamide, severe alterations were found in the tibialis anterior muscle.…”

Section: Ache Molecular Form Concentration In Musclesmentioning

confidence: 99%

Acrylamide neuropathy and changes in the axonal transport and muscular content of the molecular forms of acetylcholinesterase

et al. 1982

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Acetylcholinesterase (AChE) is present in nervous and muscular tissues of normal chickens in four main molecular forms (G1, G2, G4, and A12), distinguishable by sedimentation analysis. In the sciatic nerve of acrylamide-poisoned chickens, the anterograde axonal transport of A12 AChE was reduced by 60%, and that of G4 by 21%, compared to control values whereas the slow axoplasmic transport of G1 and G2 was unaffected. Regarding the leg muscles, only the tibialis anterior revealed dramatic alterations in the distribution of it AChE forms coinciding with a large reduction in the number of nerve endings. In acrylamide poisoning, the AChE molecular forms were considered as very sensitive markers of both axonal transport phases and of the innervation state. Our results support the hypothesis that a defect in the fast axonal transport of proteins might be involved in the degeneration process of the disease.

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‘Acrylamide-induced’ neuropathy and impairment of axonal transport of proteins. I. Multifocal retention of fast transported proteins at the periphery of axons as revealed by light microscope radioautography

Cited by 40 publications

References 14 publications

Functional consequences of repeated organophosphate exposure: Potential non-cholinergic mechanisms

Functional consequences of repeated organophosphate exposure: Potential non-cholinergic mechanisms

Repeated Exposures to Subthreshold Doses of Chlorpyrifos in Rats: Hippocampal Damage, Impaired Axonal Transport, and Deficits in Spatial Learning

Acrylamide neuropathy and changes in the axonal transport and muscular content of the molecular forms of acetylcholinesterase

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