SN56 basal forebrain cholinergic neuronal loss after acute and long-term chlorpyrifos exposure through oxidative stress generation; P75NTR and α7-nAChRs alterations mediated partially by AChE variants disruption

Pino, Javier del; Moyano, Paula; Anadón, M.J.; García, José M.; Díaz, María Jesús Villamide; Gómez, Gabriel; Frejo, María Teresa

doi:10.1016/j.tox.2016.05.007

Cited by 13 publications

(8 citation statements)

References 54 publications

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“…These results are consistent with evidence indicating no differences in p75 NTR expression in the human AD basal forebrain, aged rodent basal forebrain, or rat BFCNs aged in vitro [63,64,82,83]. However, other studies indicate that the protein levels of p75 NTR are increased by oxidative and nitrative stress induced by hydrogen peroxide, amyloid-beta, peroxynitrite, monocrotophos, and chlorpyrifos in the mouse SN56 basal forebrain cell line, human SH-SY5Y cells and retina, and rat cortex and hippocampus [128][129][130][131]. These results are consistent with other literature indicating an elevation of p75 NTR in the human AD basal forebrain and entorhinal cortex [86,88].…”

Section: Oxidative and Nitrative Stress Alter The Expression And Signalling Of Prongf Receptorssupporting

confidence: 87%

Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Kropf

Fahnestock

2021

Cells

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Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75NTR. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function.

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Section: Oxidative and Nitrative Stress Alter The Expression And Signalling Of Prongf Receptorssupporting

confidence: 87%

Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Kropf

Fahnestock

2021

Cells

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“…A previous study by Cobb and Cole emphasized that excessive ROS levels produce detrimental effects on physiological activities, especially in the nervous system. , Moreover, oxidative stress is thought to be related to a reduction in the number of cholinergic neurons . However, no dose–response relationship between these two factors was observed in the present study.…”

Section: Discussioncontrasting

confidence: 64%

Photolysis-Induced Neurotoxicity Enhancement of Chlorpyrifos in Aquatic System: A Case Investigation on Caenorhabditis elegans

Cao

Yan

Yang

et al. 2019

J. Agric. Food Chem.

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Contamination of the environment by toxic pesticides has become of great concern in agricultural countries. Chlorpyrifos (CP) is among the pesticides most commonly detected in the environment owing to its wide agricultural applications. The aim of this study was to compare potential changes in the toxicity of CP after irradiation. To this end, photolysis of CP was conducted under simulated sunlight, and neurotoxicity assessment was carried out at CP of 20 and 50 μg L–1 and its corresponding irradiated mixture solutions which contain a mixture of identified intermediates using the nematode, Caenorhabditis elegans as a model organism. Photodegradation of 20 μg L–1 CP for 1 h produced no obvious reduction of physiological damage, and more serious effects on animal movement were detected after exposure of the animals to a solution of 50 μg L–1 for 1 h irradiation compared with unirradiated solution. GABAergic and cholinergic neurons were selectively vulnerable to CP exposure, and maximal neuropathological alterations were observed after 1 h irradiation of the CP solutions in coherence with the behavioral impairment. The generation of photoproducts was considered to be responsible for the enhanced disturbance on those biological processes. This work provided useful information on the toxicological assessments of chemicals that were produced during the environmental transformation of pesticides.

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“…Acute poisoning with organophosphates has previously been shown to result in a robust opening of the blood-brain barrier, 27 while injury to the basal forebrain has previously been shown (in animal studies) following acute or chronic exposure to organophosphates. 28 Slowing of brain activity, although not a specific finding, has also been previously reported to follow exposure to organophosphates. 29…”

Section: Discussionmentioning

confidence: 88%

Havana Syndrome Among Canadian Diplomats: Brain Imaging Reveals Acquired Neurotoxicity

Friedman

Calkin

Adams

et al. 2019

Preprint

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BACKGROUND: In late 2016, US diplomats stationed in Havana began presenting with a variety of neurological manifestations that proved difficult to diagnose. Though previous studies suggested a likely association with brain injury, the mechanism of injury, brain regions involved, and etiology remained unknown. METHODS: We conducted a multimodal study examining 26 Canadian diplomats and their family members, the majority of whom presented with symptoms similar to their American counterparts while residing in Havana. Assessments included a medical history, self-reported symptom questionnaires, cognitive assessments, blood tests, and brain imaging assessments (magnetic resonance imaging (MRI) and magnetoencephalography (MEG)). Individuals showing signs of brain injury underwent further neurological, visual, and audio-vestibular assessments. Eight participants were tested both before and after living in Havana. RESULTS: Our assessment documents multiple functional and structural impairments, including significant spatial memory impairment, abnormal brain-stem evoked potentials, degradation of fibre tracts in the fornix and posterior corpus callosum, blood-brain barrier injury to the right basal forebrain and anterior insula, and abnormal paroxysmal slowing events of cortical activity. Subsequent mass-spectrometry and blood analyses documented reduced serum cholinesterase activity and the presence of organophosphates (Temephos) and pyrethroid metabolites (3-phenoxybenzoic acid or 3-BPA). CONCLUSIONS: Our findings confirm brain injury, specify the regions involved, and raise the hypothesis of overexposure to cholinesterase inhibitors as a plausible etiology. If correct, our hypothesis bears public health ramifications (see Discussion) and suggests a course of action for reducing exposure in the future. FUNDING: Global Affairs Canada.

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SN56 basal forebrain cholinergic neuronal loss after acute and long-term chlorpyrifos exposure through oxidative stress generation; P75NTR and α7-nAChRs alterations mediated partially by AChE variants disruption

Cited by 13 publications

References 54 publications

Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Photolysis-Induced Neurotoxicity Enhancement of Chlorpyrifos in Aquatic System: A Case Investigation on Caenorhabditis elegans

Havana Syndrome Among Canadian Diplomats: Brain Imaging Reveals Acquired Neurotoxicity

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