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Pyridostigmine Bromide and Stress Interact to Impact Immune Function, Cholinergic Neurochemistry and Behavior in a Rat Model of Gulf War Illness

Pyridostigmine Bromide and Stress Interact to Impact Immune Function, Cholinergic Neurochemistry and Behavior in a Rat Model of Gulf War Illness

V A Macht, J L Woodruff, E S Maissy, C A Grillo, M A Wilson, J R Fadel, L P Reagan

Brain Behav Immun. 2019 Aug;80:384-393.

PMID: 30953774

Abstract:

Gulf War Illness (GWI) is characterized by a constellation of symptoms that includes cognitive dysfunction. While the causes for GWI remain unknown, prophylactic use of the acetylcholinesterase inhibitor pyridostigmine bromide (PB) in combination with the stress of deployment has been proposed to be among the causes of the cognitive dysfunction in GWI. Mechanistically, clinical studies suggest that altered immune function may be an underlying factor in the neurochemical and neurobehavioral complications of GWI. Accordingly, the goal of this study was to determine how responses to an immune challenge (lipopolysaccharide; LPS) or stress impacts inflammation, acetylcholine (ACh) neurochemistry and behavior in an experimental model of GWI. Rats with a history of PB treatment exhibited potentiated increases in C-reactive protein levels in response to a submaximal LPS challenge compared to control rats, indicating that prior treatment with this cholinesterase inhibitor leads to exacerbated inflammatory responses to a subsequent immune challenge. ACh responses to LPS administration were decreased in the hippocampus, but not prefrontal cortex (PFC), in rats with a prior history of PB treatment or stress exposure. Additionally, ACh release in response to acute immobilization stress was attenuated in the PFC and hippocampus in these groups. These attenuated cholinergic responses were accompanied by impairments in contextual and cue-based fear learning. The results of this study suggest that stress and LPS challenges adversely affect central ACh neurochemistry in a rodent model of GWI and support the hypothesis that dysregulated immune responses are mechanistically linked to the neurological complications of GWI.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP101268-A	Pyridostigmine bromide		101-26-8	Price

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