Prolonged activation of CXCR4 hampers the release-regulating activity of presynaptic NMDA receptors in rat hippocampal synaptosomes.
Neurochem Int
; 126: 59-63, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30858017
ABSTRACT
We investigated the impact of the prolonged exposure of rat hippocampal synaptosomes to CXCL12 (3â¯nM) on the NMDA-mediated release of [3H]D-aspartate ([3H]D-Asp) or [3H]noradrenaline ([3H]NA). Synaptosomes were stimulated twice with NMDA/CXCL12 and the amount of the NMDA-evoked tritium release (S1 and S2) quantified to calculate the S2/S1 ratio. The S2/S1 ratio for both transmitters was drastically decreased by 3â¯nM CXCL12 between the two stimuli (CXCL12-treated synaptosomes) in a AMD3100-sensitive manner. The phosphorylation of the GluN1 subunit in Ser 896 was reduced in CXCL12-treated synaptosomes, while the overall amount of GluN1 and GluN2B proteins as well as the GluN2B insertion in synaptosomal plasmamembranes were unchanged. We conclude that the CXCR4/NMDA cross-talk is dynamically regulated by the time of activation of the CXCR4s. Our results unveil a functional cross-talk that might account for the severe impairments of central transmission that develop in pathological conditions characterized by CXCL12 overproduction.
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MEDLINE
Assunto principal:
Sinaptossomos
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Receptores de N-Metil-D-Aspartato
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Terminações Pré-Sinápticas
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Receptores CXCR4
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Hipocampo
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article