Neurotoxicity in Gulf War Illness and the Potential Role of Glutamate, 2020, Joyce and Holton

Andy · Jun 26, 2020

Shortly after the Gulf War in 1990-1991, service men and women began reporting multiple symptoms ranging from persistent headaches, widespread pain, chronic fatigue, cognitive dysfunction, mood dysregulation, gastrointestinal issues, skin abnormalities, and respiratory problems. This prompted the Centers for Disease Control and Prevention (CDC) to initially classify the disorder as chronic multi-symptom illness (CMI), where it later became known as Gulf War Illness (GWI).

Researchers and healthcare professionals since the early 1990s have been working extensively on alleviating the symptoms expressed in GWI as well as attempting to understand the mechanisms behind this illness. Scientific literature as well as reports from GWI veterans indicate that the toxic exposures during deployment may be responsible for the symptoms. These toxic exposures potentially include nerve agents, pyridostigmine bromide pills, pesticides, munitions with depleted uranium, and burning oil well fires. GWI currently affects 25-32% of the 697,000 American troops who were stationed overseas during the short conflict.

The purpose of this paper is to review the literature on neurotoxic exposures in Gulf War Illness, to explain how these exposures may lead to glutamate excitotoxicity, which has been implicated in the majority of the symptoms characterizing the illness, and to propose a novel treatment option for GWI.
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Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0161813X20300954
Not available via Sci hub at time of posting.

mariovitali · Jun 26, 2020

This is very interesting. For the people that have been following the research using Machine Learning methods, there was a hypothesis -since 2015- that Gulf War Illness Syndrome, Post Finasteride Syndrome , Post-treatment Lyme disease syndrome and ME/CFS have common mechanisms.

Here is a recent tweet on Pesticides (more specifically Organophosphates) one of the most important aspects is that we have people getting ME from other means apart viruses. Observe the role of Glutamate on Organophosphate (OP) poisoning here as well:

https://twitter.com/user/status/1275748376831832066

Midnattsol · Jun 26, 2020

But glutamate is not very specific. It can also be affected by lifestyle factors like diet and activity levels. Excitotoxicity is also linked to suicide ideation, psychosis, major depression, autism, I guess cognitive impairment (can't remember) and the whole glutamine/glutamate relationship and how it's important for metabolism.

I believe it's important, you don't want dysregulation of glutamate, but I'd be more surprised if they hadn't found anything.

mariovitali · Jun 26, 2020

This is true. I am very excited with the DecodeME project because the number of data will help us identify subtypes that potentially lead to the same result. What i am trying to say is that we may have not only issues with Glutamate but also with Glutathione production (an example). Another subtype may have issues with Cysteine catabolism. These with a minor issue in mitochondrial functioning could make the perfect storm. As you know i am not a medical professional, these are just speculations.

Midnattsol · Jun 26, 2020

mariovitali said: ↑

This is true. I am very excited with the DecodeME project because the number of data will help us identify subtypes that potentially lead to the same result. What i am trying to say is that we may have not only issues with Glutamate but also with Glutathione production (an example). Another subtype may have issues with Cysteine catabolism. These with a minor issue in mitochondrial functioning could make the perfect storm. As you know i am not a medical professional, these are just speculations.
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I agree, DecodeME is going to be fascinating!

Glutamate, glutathione, cysteine and mitochondria is very interesting as well, especially for a nutritionist/cell biologist

spinoza577 · Jun 26, 2020

Midnattsol said: ↑

Excitotoxicity is also linked to suicide ideation, psychosis, major depression, autism, I guess cognitive impairment (can't remember) and ...
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Midnattsol · Jun 27, 2020

spinoza577 said: ↑

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The worst is I did not think about the obvious pun when I wrote it

mariovitali · Jul 12, 2020

paper is now available on Scihub :

https://sci-hub.tw/10.1016/j.neuro.2020.06.008

mariovitali · Jul 12, 2020

I realised that pyridostigmine bromide - PB (aka MESTINON) is hypothesised as one of the causes of Gulf War Illness :

Macht and colleagues discuss the implications of disrupted glutamatergic systems that typically mediate the glial immune response and neurotoxicity in rodent models, where PB may disrupt the glutamatergic system of the prefrontal cortex (PFC) for novel stressful stimuli and affect encoding events within the hippocampus (Macht et al., 2020). Specifically, this may relate to GW veterans exposed to novel stressors and the glutamatergic system failing to respond, typically leading to subsequent excitotoxicity
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Neurotoxicity in Gulf War Illness and the Potential Role of Glutamate, 2020, Joyce and Holton

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