Identification of Non-excitatory Amino Acids and Transporters Mediating the Irreversible Synaptic Silencing After Hypoxia.
ASCT2
Amino acid transporters
Glutamate receptors
Hippocampus
Hypoxia
Swelling
Synaptic transmission
Journal
Translational stroke research
ISSN: 1868-601X
Titre abrégé: Transl Stroke Res
Pays: United States
ID NLM: 101517297
Informations de publication
Date de publication:
27 Sep 2023
27 Sep 2023
Historique:
received:
02
06
2023
accepted:
01
09
2023
revised:
03
08
2023
medline:
27
9
2023
pubmed:
27
9
2023
entrez:
27
9
2023
Statut:
aheadofprint
Résumé
The contribution of excitatory amino acids (AA) to ischemic brain injury has been widely described. In addition, we reported that a mixture of non-excitatory AA at plasmatic concentrations turns irreversible the depression of synaptic transmission caused by hypoxia. Here, we describe that the presence of seven non-excitatory AA (L-alanine, L-glutamine, glycine, L-histidine, L-serine, taurine, and L-threonine) during hypoxia provokes an irreversible neuronal membrane depolarization, after an initial phase of hyperpolarization. The collapse of the membrane potential correlates with a great increase in fiber volley amplitude. Nevertheless, we show that the presence of all seven AA is not necessary to cause the irreversible loss of fEPSP after hypoxia and that the minimal combination of AA able to provoke a solid, replicable effect is the mixture of L-alanine, glycine, L-glutamine, and L-serine. Additionally, L-glutamine seems necessary but insufficient to induce these harmful effects. We also prove that the deleterious effects of the AA mixtures on field potentials during hypoxia depend on both the identity and concentration of the individual AA in the mixture. Furthermore, we find that the accumulation of AA in the whole slice does not determine the outcome caused by the AA mixtures on the synaptic transmission during hypoxia. Finally, results obtained using pharmacological inhibitors and specific substrates of AA transporters suggest that system N and the alanine-serine-cysteine transporter 2 (ASCT2) participate in the non-excitatory AA-mediated deleterious effects during hypoxia. Thus, these AA transporters might represent therapeutical targets for the treatment of brain ischemia.
Identifiants
pubmed: 37755645
doi: 10.1007/s12975-023-01192-y
pii: 10.1007/s12975-023-01192-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : "Ministerio de Universidades" of the Spanish government
ID : PID2021-128133NB-I00
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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