Do vasoactive neuropeptide autoimmune disorders explain pyridostigmine’s association with Gulf War syndrome?

Staines, Donald

doi:10.1016/j.mehy.2005.02.036

Cited by 8 publications

(4 citation statements)

References 26 publications

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“…, impairs mental development (Engel et al 2011), and causes cognitive deficits (Eaton et al 2008;Bouchard et al 2010;Rauh et al 2011). Furthermore, exposure to cholinesterase-inhibiting compounds including OP, pesticides, pyridostigmine bromide (PB, an anti-nerve agent medication), and low-level sarin nerve gas is linked epidemiologically with a chronic multi-symptom illness in veterans from the Persian Gulf War (Staines 2005;Thomas et al 2006;Haley et al 2009). Symptoms include cognitive disturbances, muscle fatigue, fever, diarrhea, and insomnia.…”

Section: )mentioning

confidence: 99%

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Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum

Torres-Altoro

Mathur

Drerup

et al. 2011

Journal of Neurochemistry

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The neurological effects of organophosphate pesticides, commonly used on foods and in households, are an important public health concern. Furthermore, subclinical exposure to combinations of organophosphates is implicated in Gulf War illness. Here we characterized the effects of the broadly-used insecticide chlorpyrifos on dopamine and glutamatergic neurotransmission effectors in corticostriatal motor/reward circuitry. Chlorpyrifos potentiated PKA-dependent phosphorylation of the striatal protein DARPP-32 and the GluR1 subunit of AMPA receptors in mouse brain slices. It also increased GluR1 phosphorylation by PKA when administered systemically. This correlated with enhanced glutamate release from cortical projections in rat striatum. Similar effects were induced by the sarin congener, diisopropyl fluorophosphate, alone or in combination with the putative neuroprotectant, pyridostigmine bromide and the pesticide DEET. This combination, meant to mimic the neurotoxicant exposure encountered by veterans of the 1991 Persian Gulf War, also induced hyperphosphorylation of the neurofibrillary tangle-associated protein tau. Diisopropyl fluorophosphate and pyrodostigmine bromide, alone or in combination, also increased the aberrant activity of the protein kinase, Cdk5, as indicated by conversion of its activating cofactor p35 to p25. Thus consistent with recent findings in humans and animals, organophosphate exposure causes dysregulation in the motor/reward circuitry and invokes mechanisms associated with neurological disorders and neurodegeneration.

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Section: )mentioning

confidence: 99%

“…2011). Furthermore, exposure to cholinesterase‐inhibiting compounds including OP, pesticides, pyridostigmine bromide (PB, an anti‐nerve agent medication), and low‐level sarin nerve gas is linked epidemiologically with a chronic multi‐symptom illness in veterans from the Persian Gulf War (Staines 2005; Thomas et al. 2006; Haley et al.…”

mentioning

confidence: 99%

Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum

Torres-Altoro

Mathur

Drerup

et al. 2011

Journal of Neurochemistry

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“…In addition, chemical sensitivity and odour intolerance have been reported. The aetiology of the condition is unclear, but many reviews and epidemiological analyses suggest association with pyridostigmine bromide (PB) 4,5 use as nerve gas prophylaxis, insect repellent, certain vaccination regimes, a variety of possible chemical exposures 6 including smoke from oil-well fires 7 or depleted uranium from shells, 8 as well as physical and psychological stress.…”

Section: Introductionmentioning

confidence: 99%

Gulf War Syndrome as a part of the autoimmune (autoinflammatory) syndrome induced by adjuvant (ASIA)

Israeli¹

2012

Lupus

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Gulf War syndrome (GWS) is a multi-symptom condition comprising a variety of signs and symptoms described in the literature, which not been fully resolved. The various symptoms of the condition include muscle fatigue and tiredness, malaise, myalgia, impaired cognition, ataxia, diarrhoea, bladder dysfunction, sweating disturbances, headaches, fever, arthralgia, skin rashes, and gastrointestinal and sleep disturbances. In addition, excessive chemical sensitivity and odour intolerance is reported. The aetiology of the condition is unclear, but many reviews and epidemiological analyses suggest association with pyridostigmine bromide (PB), certain vaccination regimes, a variety of possible chemical exposures, including smoke from oil-well fires or depleted uranium from shells, as well as physical and psychological stress. Recently, Shoenfeld et al. suggested that four conditions--siliconosis, macrophagic myofaciitis (MMF), GWS and post-vaccination phenomena--that share clinical and pathogenic resemblances, may be incorporated into common syndrome called 'Autoimmune (Autoinflammatory) Syndrome induced by Adjuvants' (ASIA). Symptoms and signs of the four conditions described by Shoenfeld et al. show that at least eight out of ten main symptoms are in correlation in all four conditions. Namely, myalgia, arthralgias, chronic fatigue, neurological cognitive impairment, gastrointestinal symptoms, respiratory symptoms, skin manifestations and appearance of autoantibodies. Regardless of the aetiology of GWS, be it exposure to environmental factors or chemical drugs, vaccinations or the adjuvants in them, GWS fits well with the definition of ASIA and is included as part of 'Shoenfeld's syndrome'.

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“…It is interesting to note as well that a small number of diseases and disorders have been linked to PACAP autoimmunity. Autoimmune dysfunction of endogenous vasoactive neuropeptides such as VIP and PACAP has been proposed as a cause for fatigue-related conditions such as multiple sclerosis, amyotrophic lateral sclerosis, and Gulf War Syndrome (Staines, 2005, 2008). These syndromes share common pathogenic features including inflammation, oxidative stress, and mitochondrial dysfunction.…”

Section: Pituitary Adenylate Cyclase Activating Peptide (Pacap)mentioning

confidence: 99%

Chemical modification of Class II G protein-coupled receptor ligands: Frontiers in the development of peptide analogs as neuroendocrine pharmacological therapies

Chapter

White

DeRidder

et al. 2010

Pharmacology & Therapeutics

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Recent research and clinical data have begun to demonstrate the huge potential therapeutic importance of ligands that modulate the activity of the secretin-like, Class II, G-protein coupled receptors (GPCRs). Ligands that can modulate the activity of these Class II GPCRs may have important clinical roles in the treatment of a wide variety of conditions such as osteoporosis, diabetes, amyotrophic lateral sclerosis and autism spectrum disorders. While these receptors present important new therapeutic targets, the large glycoprotein nature of their cognate ligands poses many problems with respect to therapeutic peptidergic drug design. These native peptides often exhibit poor bioavailability, metabolic instability, poor receptor selectivity and resultant low potencies in vivo. Recently, increased attention has been paid to the structural modification of these peptides to enhance their therapeutic efficacy. Successful modification strategies have included D-amino acid substitutions, selective truncation, and fatty acid acylation of the peptide. Through these and other processes, these novel peptide ligand analogs can demonstrate enhanced receptor subtype selectivity, directed signal transduction pathway activation, resistance to proteolytic degradation, and improved systemic bioavailability. In the future, it is likely, through additional modification strategies such as addition of circulation-stabilizing transferrin moieties, that the therapeutic pharmacopeia of drugs targeted towards Class II secretin-like receptors may rival that of the Class I rhodopsin-like receptors that currently provide the majority of clinically used GPCR-based therapeutics. Currently, Class IIbased drugs include synthesized analogues of vasoactive intestinal peptide for type 2 diabetes or parathyroid hormone for osteoporosis.

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Do vasoactive neuropeptide autoimmune disorders explain pyridostigmine’s association with Gulf War syndrome?

Cited by 8 publications

References 26 publications

Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum

Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum

Gulf War Syndrome as a part of the autoimmune (autoinflammatory) syndrome induced by adjuvant (ASIA)

Chemical modification of Class II G protein-coupled receptor ligands: Frontiers in the development of peptide analogs as neuroendocrine pharmacological therapies

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