Rats were given glycyl-L-glutamine (Gly-Gln) by intraaortic infusion with Alzet osmotic pumps during the 48-hr period following the intraaortic administration of diisopropyl phosphorofluoridate (DFP) (10 mumol/kg). The infusion of 1.2 mumol of Gly-Gln per 24 hr resulted in a significant increase in the acetylcholinesterase (AcChoEase; acetylcholine acetylhydrolase, EC 3.1.1.7) activity of the gastrocnemius muscles over that of rats that received DFP only. At a total dose of 3.6 mumol per 24 hr, a diminished result was obtained; at 0.36 mumol per 24 hr, no effect was detectable. These findings, together with earlier ones, suggest that the neurotrophic effect of Gly-Gln or a similar endogenous factor on AcChoEase synthesis is a general phenomenon at sites of cholinergic transmission.
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http://dx.doi.org/10.1073/pnas.86.11.4331 | DOI Listing |
J Neuroinflammation
November 2024
Department of Molecular Biosciences, Davis, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication.
View Article and Find Full Text PDFNeuropharmacology
February 2025
Department of Neuroscience, Universidad Central del Caribe, Bayamón, PR, 00956, USA. Electronic address:
Gulf War Illness (GWI) has been consistently linked to exposure to pyridostigmine (PB), N,N-Diethyl-meta-toluamide (DEET), permethrin (PER), and traces of sarin. In this study, diisopropylfluorophosphate (DFP, sarin surrogate) and the GWI-related chemicals were found to reduce the number of functionally active neurons in rat hippocampal slices. These findings confirm a link between GWI neurotoxicants and N-Methyl-D-Aspartate (NMDA)-mediated excitotoxicity, which was successfully reversed by Edelfosine (a phospholipase Cβ (PLCβ3) inhibitor) and Flupirtine (a Kv7 channel agonist).
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
The colorless and odorless nerve agents can cause paralysis and even death. The development of novel composite-based microporous strips has allowed for the rapid and visual detection of diisopropyl phosphorofluoridate (DIPF) nerve agent mimics. The active methyl-containing tricyanofuran and 4-aminobenzotrifluoride diazonium salt were azo-coupled in a straightforward manner to produce a new benzotrifluoride (BFT)-comprising tricyanofuran (TCF) hydrazone colorimetric probe.
View Article and Find Full Text PDFNeuropharmacology
June 2024
Department of Molecular Biosciences, University of California, Davis, School of Veterinary Medicine, Davis, CA 95616, USA. Electronic address:
Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures.
View Article and Find Full Text PDFNeuropharmacology
May 2024
Department of Molecular Biosciences, University of California-Davis School of Veterinary Medicine, Davis, CA, 95616, USA. Electronic address:
Acute intoxication with organophosphate (OP) cholinesterase inhibitors poses a significant public health risk. While currently approved medical countermeasures can improve survival rates, they often fail to prevent chronic neurological damage. Therefore, there is need to develop effective therapies and quantitative metrics for assessing OP-induced brain injury and its rescue by these therapies.
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