ArticleToxicological sciences : an official journal of the Society of Toxicology2012
Tetramethylenedisulfotetramine alters Ca²⁺ dynamics in cultured hippocampal neurons: mitigation by NMDA receptor blockade and GABA(A) receptor-positive modulation.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 45 citations in OpenAlex.
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- Novel neurosteroid pregnanolone pyroglutamate suppresses neurotoxicity syndrome induced by tetramethylenedisulfotetramine but is ineffective in a rodent model of infantile spasms.Pharmacological reports : PR · 2023Article
- Gene×environment interactions in autism spectrum disorders.Current topics in developmental biology · 2023Review
- Integrating Data From In Vitro New Approach Methodologies for Developmental Neurotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Structure-Activity Relationship of Neuroactive Steroids, Midazolam, and Perampanel Toward Mitigating Tetramine-Triggered Activity in Murine Hippocampal Neuronal Networks.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Article
- Allopregnanolone and perampanel as adjuncts to midazolam for treating diisopropylfluorophosphate-induced status epilepticus in rats.Annals of the New York Academy of Sciences · 2020Article
- Tetramethylenedisulfotetramine neurotoxicity: What have we learned in the past 70 years?Neurobiology of disease · 2020Review
- Susceptibility of larval zebrafish to the seizurogenic activity of GABA type A receptor antagonists.Neurotoxicology · 2020Article
- Influence of Nanomolar Deltamethrin on the Hallmarks of Primary Cultured Cortical Neuronal Network and the Role of Ryanodine Receptors.Environmental health perspectives · 2019Article
- Functional and Mechanistic Neurotoxicity Profiling Using Human iPSC-Derived Neural 3D Cultures.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Tetramethylenedisulfotetramine: A Health Risk Compound and a Potential Chemical Warfare Agent.Toxics · 2018Review
- Developmental and sex differences in tetramethylenedisulfotetramine (TMDT)-induced syndrome in rats.Developmental neurobiology · 2018Article
- GABAArchives of toxicology · 2018Article
- Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex.Journal of neuroinflammation · 2018Article
- Behavioral intoxication following voluntary oral ingestion of tetramethylenedisulfotetramine: Dose-dependent onset, severity, survival, and recovery.Neurotoxicology · 2017Article
- Rapid Throughput Analysis of GABAMolecular pharmacology · 2017Article
- Development of Tetramethylenedisulfotetramine (TETS) Hapten Library: Synthesis, Electrophysiological Studies, and Immune Response in Rabbits.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
- Mutant IDH1 and seizures in patients with glioma.Neurology · 2017Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tetramethylenedisulfotetramine (TETS) is a potent convulsant that is considered a chemical threat agent. We characterized TETS as an activator of spontaneous Ca²⁺ oscillations and electrical burst discharges in mouse hippocampal neuronal cultures at 13-17 days in vitro using FLIPR Fluo-4 fluorescence measurements and extracellular microelectrode array recording. Acute exposure to TETS (≥ 2 µM) reversibly altered the pattern of spontaneous neuronal discharges, producing clustered burst firing and an overall increase in discharge frequency. TETS also dramatically affected Ca²⁺ dynamics causing an immediate but transient elevation of neuronal intracellular Ca²⁺ followed by decreased frequency of Ca²⁺ oscillations but greater peak amplitude. The effect on Ca²⁺ dynamics was similar to that elicited by picrotoxin and bicuculline, supporting the view that TETS acts by inhibiting type A gamma-aminobutyric acid (GABA(A)) receptor function. The effect of TETS on Ca²⁺ dynamics requires activation of N-methyl-D-aspartic acid (NMDA) receptors, because the changes induced by TETS were prevented by MK-801 block of NMDA receptors, but not nifedipine block of L-type Ca²⁺ channels. Pretreatment with the GABA(A) receptor-positive modulators diazepam and allopregnanolone partially mitigated TETS-induced changes in Ca²⁺ dynamics. Moreover, low, minimally effective concentrations of diazepam (0.1 µM) and allopregnanolone (0.1 µM), when administered together, were highly effective in suppressing TETS-induced alterations in Ca²⁺ dynamics, suggesting that the combination of positive modulators of synaptic and extrasynaptic GABA(A) receptors may have therapeutic potential. These rapid throughput in vitro assays may assist in the identification of single agents or combinations that have utility in the treatment of TETS intoxication.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.