Involvement of Notch signaling in hippocampal synaptic plasticity

Abstract

During development of the nervous system, the fate of stem cells is regulated by a cell surface receptor called Notch. Notch is also present in the adult mammalian brain; however, because Notch null mice die during embryonic development, it has proven difficult to determine the functions of Notch. Here, we used Notch antisense transgenic mice that develop and reproduce normally, but exhibit reduced levels of Notch, to demonstrate a role for Notch signaling in synaptic plasticity. Mice with reduced Notch levels exhibit impaired long-term potentiation (LTP) at hippocampal CA1 synapses. A Notch ligand enhances LTP in normal mice and corrects the defect in LTP in Notch antisense transgenic mice. Levels of basal and stimulation-induced NF-κB activity were significantly decreased in mice with reduced Notch levels. These findings suggest an important role for Notch signaling in a form of synaptic plasticity known to be associated with learning and memory processes.

Retracted: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells

“…Levels of basal and stimulation-induced NF-jB activity were significantly decreased in mice with reduced Notch levels. 28 Constitutive levels of Notch activity are essential to maintain NFjB activity in various cell types. Notch and NF-jB pathways are key regulators of numerous cellular processes such as proliferation, differentiation and apoptosis.…”

Rhamnetin and Cirsiliol Induce Radiosensitization and Inhibition of Epithelial-Mesenchymal Transition (EMT) by miR-34a-mediated Suppression of Notch-1 Expression in Non-small Cell Lung Cancer Cell Lines

“…5). Because NF-B pathways are key regulators of numerous cellular processes such as proliferation, differentiation, and inflammation, our results clearly provide molecular evidence for potential crosstalk between Notch-1 and NF-B pathways and suggest that cell growth inhibition and apoptosis promoted by the downregulation of Notch-1 after treatment of rhamnetin and cirsiliol may be partly mediated by NF-B (73)(74)(75). Because an approach using Notch-1 siRNA is not yet practical for therapeutic purposes, we recommend the use of rhamnetin and cirsiliol found to be potent agents capable of regulating NF-B pathway by Notch-1 inhibition.…”

The APP-interacting protein FE65 is required for hippocampus-dependent learning and long-term potentiation

“…Interestingly, FE65 also interacts with the intracellular domain of Notch, and it has been suggested that Notch and APP may regulate a number of same target genes (Fischer et al 2005). Mice with a reduced level of Notch display defects in both LTP and spatial learning (Costa et al 2003;Wang et al 2004b). Because certain regulatory functions may be shared by FE65s (FE65, FE65L1, and FE65L2), using neurons derived from double-or triple-mutants will facilitate the understanding of how the FE65 family participates in the complex signaling network.…”