Linking activation of synaptic NMDA receptors-induced CREB signaling to brief exposure of cortical neurons to oligomeric amyloid-beta peptide.

Autor: Ferreira IL; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal., Marinho D; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal., de Rosa V; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal., Castanheira B; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal., Fang Z; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal., Caldeira GL; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal., Mota SI; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal., Rego AC; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2025 Jan; Vol. 169 (1), pp. e16222. Date of Electronic Publication: 2024 Sep 12.
DOI: 10.1111/jnc.16222
Abstrakt: Amyloid-beta peptide oligomers (AβO) have been considered "primum movens" for a cascade of events that ultimately cause selective neuronal death in Alzheimer's disease (AD). However, initial events triggered by AβO have not been clearly defined. Synaptic (Syn) N-methyl-d-aspartate receptors (NMDAR) are known to activate cAMP response element-binding protein (CREB), a transcriptional factor involved in gene expression related to cell survival, memory formation and synaptic plasticity, whereas activation of extrasynaptic (ESyn) NMDARs was linked to excitotoxic events. In AD brain, CREB phosphorylation/activation was shown to be altered, along with dyshomeostasis of intracellular Ca 2+ (Ca 2+ i ). Thus, in this work, we analyze acute/early and long-term AβO-mediated changes in CREB activation involving Syn or ESyn NMDARs in mature rat cortical neurons. Our findings show that acute AβO exposure produce early increase in phosphorylated CREB, reflecting CREB activity, in a process occurring through Syn NMDAR-mediated Ca 2+ influx. Data also demonstrate that AβO long-term (24 h) exposure compromises synaptic function related to Ca 2+ -dependent CREB phosphorylation/activation and nuclear CREB levels and related target genes, namely Bdnf, Gadd45γ, and Btg2. Data suggest a dual effect of AβO following early or prolonged exposure in mature cortical neurons through the activation of the CREB signaling pathway, linked to the activation of Syn NMDARs.
(© 2024 International Society for Neurochemistry.)
Databáze: MEDLINE
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