Anoxia-induced Hippocampal LTP is Regeneratively Produced by Glutamate and Nitric Oxide from the Neuro-glial-endothelial Axis

Overview

Journal iScience

Publisher Cell Press

Date 2024 Apr 9

PMID 38591010

Authors

Han-Ying Wang

Hiroshi Takagi

Patrick N Stoney

Anai Echeverria

Bernd Kuhn

Kuei-Sen Hsu

Tomoyuki Takahashi

Affiliations

Soon will be listed here.

Abstract

Transient anoxia causes amnesia and neuronal death. This is attributed to enhanced glutamate release and modeled as anoxia-induced long-term potentiation (aLTP). aLTP is mediated by glutamate receptors and nitric oxide (·NO) and occludes stimulation-induced LTP. We identified a signaling cascade downstream of ·NO leading to glutamate release and a glutamate-·NO loop regeneratively boosting aLTP. aLTP in entothelial ·NO synthase (eNOS)-knockout mice and blocking neuronal NOS (nNOS) activity suggested that both nNOS and eNOS contribute to aLTP. Immunostaining result showed that eNOS is predominantly expressed in vascular endothelia. Transient anoxia induced a long-lasting Ca elevation in astrocytes that mirrored aLTP. Blocking astrocyte metabolism or depletion of the NMDA receptor ligand D-serine abolished eNOS-dependent aLTP, suggesting that astrocytic Ca elevation stimulates D-serine release from endfeet to endothelia, thereby releasing ·NO synthesized by eNOS. Thus, the neuro-glial-endothelial axis is involved in long-term enhancement of glutamate release after transient anoxia.

Citing Articles

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