Regulation of extracellular signal-regulated kinase by homocysteine in hippocampus.
type: Distribution
access URL: https://hal.science/hal-00084958
format: HTML
issued: 2026-05-10T04:25:37.946386
modified: 2026-05-10T04:25:37.930290

test_moissonnage_selune
type: Agent

Regulation of extracellular signal-regulated kinase by homocysteine in hippocampus.
type: Dataset
contact point: Organization
  fn: CCSD
keyword: infoeu-reposemanticsarticle
keyword: journal-articles
keyword: sdvneusclife-sciences-q-bioneurons-and-cognition-q-bionccognitive-sciences
keyword: creb
keyword: homocysteine
keyword: metabotropic-glutamate-receptors
keyword: ionotropic-receptors
keyword: extracellular-signal-regulated-protein-kinase
keyword: synaptic-transmission
landing page: 0306-4522
description: In several neurological disorders including hyperhomocysteinemia, homocysteine (Hcy) accumulates in the brain, and acts as a potent neurotoxin. However, the molecular mechanisms induced by increased levels of Hcy in brain are not well understood. Here we show an activation of the extracellular signal-regulated kinases (ERK1 and ERK2) and the downstream nuclear targets Elk-1 and calcium/cAMP response element binding protein, in the hippocampus of cystathionine beta synthase deficient mice, a murine model of hyperhomocysteinemia. An ex vivo model of hippocampal slices allowed us to reproduce Hcy -induced ERK activation and to unravel the mechanisms responsible of this activation. Of interest, N-methyl-d-aspartate (NMDA), non-NMDA and metabotropic glutamate receptor antagonists all blocked Hcy -induced ERK activation. Moreover, the ERK activation was blocked in the presence of Na+-channel blocker tetrodotoxin, indicating the existence of a trans-synaptic activity in ERK activation by Hcy in hippocampal slices. The effects of Hcy on ERK cascade activation were also dependent on calcium influx, CaMK-II, PKC as well as PKA activation. Thus, altogether these data support a role of Hcy on ERK activation, via complex mechanisms, starting with a control of glutamate release, which in turn activates ionotropic and metabotropic receptor subtypes and produces increases in intracellular calcium levels.
issued: 2026-05-10T04:25:37.941464
language: en
modified: 2026-05-10T04:25:37.941469