Activity-Induced Notch Signaling in Neurons Requires Arc/Arg3.1 and Is Essential for Synaptic Plasticity in Hippocampal Networks

Albèri, Lavinia; Liu, Shuxi; Wang, Yue; Badie, Ramy; Smith‐Hicks, Constance; Wu, Jing; Pierfelice, Tarran J.; Abazyan, Bagrat; Mattson, Mark P.; Kuhl, Dietmar; Pletnikov, Mikhail V.; Worley, Paul F.; Gaiano, Nicholas

doi:10.1016/j.neuron.2011.01.004

Cited by 185 publications

(280 citation statements)

References 33 publications

Supporting

Mentioning

259

Contrasting

Order By: Relevance

“…The immunohistochemistry stainings using fluorescently tagged secondary antibodies were done as described previously. 12 Transcript expression analysis by RT-qPCR. 12 h after the KA injection, mice were transcardially perfused with 0.9% saline solution.…”

Section: Discussionmentioning

confidence: 99%

“…Protein concentrations from both preparations were determined using the BCA method (Carl Roth, Karlsruhe, Germany). Notch1 immunoprecipitation was performed on the membrane enriched fractions from hippocampal CA fields 12 and hippocampal CA lysates, whereas E2F1 IP was performed on hippocampal CA fields lysates only (two bilateral CA fields per IP per condition). The homogenates were incubated for 1.5 h with 10 μg of primary antibodies or with 10 μg of Goat serum (PAA).…”

Section: Discussionmentioning

confidence: 99%

“…Notch/ RBPJK canonical signaling, is a highly conserved signaling cascade, which has an important role in nervous system development and in stem cell proliferation and maintenance. 11 Notch signaling also has crucial roles in the adult brain, in neurons 12 and neurogenic niches. 13 Notch1 appears to be an important signaling receptor in neurons regulating synaptic plasticity, and learning and memory.…”

mentioning

confidence: 99%

“…13 Notch1 appears to be an important signaling receptor in neurons regulating synaptic plasticity, and learning and memory. 12 On the other hand, overactivation of Notch signaling, in response to hypoxic-ischemic or epileptic injury appears to contribute to neuronal demise. 14,15 Here we show that excitotoxic kainic acid (KA) treatment results in S-phase reentry with concomitant nuclear localization of Notch1.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Notch signaling in response to excitotoxicity induces neurodegeneration via erroneous cell cycle reentry

et al. 2015

View full text Add to dashboard Cite

Neurological disorders such as Alzheimer's disease, stroke and epilepsy are currently marred by the lack of effective treatments to prevent neuronal death. Erroneous cell cycle reentry (CCR) is hypothesized to have a causative role in neurodegeneration. We show that forcing S-phase reentry in cultured hippocampal neurons is sufficient to induce neurodegeneration. We found that kainic-acid treatment in vivo induces erroneous CCR and neuronal death through a Notch-dependent mechanism. Ablating Notch signaling in neurons provides neuroprotection against kainic acid-induced neuronal death. We further show that kainic-acid treatment activates Notch signaling, which increases the bioavailability of CyclinD1 through Akt/GSK3β pathway, leading to aberrant CCR via activation of CyclinD1-Rb-E2F1 axis. In addition, pharmacological blockade of this pathway at critical steps is sufficient to confer resistance to kainic acid-induced neurotoxicity in mice. Taken together, our results demonstrate that excitotoxicity leads to neuronal death in a Notch-dependent manner through erroneous CCR.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Notch signaling in response to excitotoxicity induces neurodegeneration via erroneous cell cycle reentry

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In the brain, IEG induction mediates the plasticity underlying complex processes such as learning, memory, and behavior (6)(7)(8). Thus, genetic deletion of these IEGs often leads to deficits in the encoding and consolidation of longterm memory (9)(10)(11). Signaling cascades in which neural activity induces IEGs have been elusive.…”

mentioning

confidence: 99%

Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction

Paul

Smith

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Profound induction of immediate early genes (IEGs) by neural activation is a critical determinant for plasticity in the brain, but intervening molecular signals are not well characterized. We demonstrate that inositol polyphosphate multikinase (IPMK) acts noncatalytically as a transcriptional coactivator to mediate induction of numerous IEGs. IEG induction by electroconvulsive stimulation is virtually abolished in the brains of IPMK-deleted mice, which also display deficits in spatial memory. Neural activity stimulates binding of IPMK to the histone acetyltransferase CBP and enhances its recruitment to IEG promoters. Interestingly, IPMK regulation of CBP recruitment and IEG induction does not require its catalytic activities. Dominant-negative constructs, which prevent IPMK-CBP binding, substantially decrease IEG induction. As IPMK is ubiquitously expressed, its epigenetic regulation of IEGs may influence diverse nonneural and neural biologic processes.inositol phosphates | learning

show abstract

MicroRNA‐mediated non‐cell‐autonomous regulation of cortical radial glial transformation revealed by a Dicer1 knockout mouse model

Zhang

Liu

et al. 2015

Glia

View full text Add to dashboard Cite

Radial glia (RG), as neurogenic progenitors and neuronal migration scaffolds, play critical roles during cortical neurogenesis. RG transformation into astrocytes, marking the transition from developmental to physiological function of these cells, is an important step during cortical development. In this study, we aim to determine the roles of microRNAs (miRNAs) during this biological process. In a conditional Dicer1-null mouse where Dicer1 is deleted in both RG and their neuronal progeny, we observe delayed RG transformation as revealed by the persistence of their radial processes, and reduced number and complexity of translocated RG cell bodies in the postnatal cerebral cortex. Downregulation of Notch1 signaling is crucial to RG transformation, and consistently we find that Notch1 signaling is enhanced in the Dicer1-null cerebral cortex. In addition, we show that, among the Notch1 ligands, Jagged2 (Jag2) is preferentially upregulated in the postnatal Dicer1-null cerebral cortex as well as primary embryonic cortical cultures with instant Dicer1 deletion. Functionally, Dicer1-deleted postnatal cerebellar cells with elevated Jag2 expression stimulate a stronger Notch1 signaling in a RG clone L2.3 when co-cultured than control cells. Therefore, we unravel a novel non-cell-autonomous mechanism that regulates RG transformation by modulating Notch1 signaling via miRNA-mediated suppression of the Nocth1 ligand Jag2. Furthermore, we validate Jag2 as a miR-124 target gene and demonstrate in vitro that Jag2 expression is highly sensitive to Dicer1 deletion. Finally, we propose a new concept of MiRNA-Sensitive target genes, identification of which may unravel a unique mode of miRNA-mediated gene expression regulation.

show abstract

Activity-Induced Notch Signaling in Neurons Requires Arc/Arg3.1 and Is Essential for Synaptic Plasticity in Hippocampal Networks

Cited by 185 publications

References 33 publications

Notch signaling in response to excitotoxicity induces neurodegeneration via erroneous cell cycle reentry

Notch signaling in response to excitotoxicity induces neurodegeneration via erroneous cell cycle reentry

Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction

MicroRNA‐mediated non‐cell‐autonomous regulation of cortical radial glial transformation revealed by a Dicer1 knockout mouse model

Contact Info

Product

Resources

About