Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

Pustylnyak, Vladimir O.; Lisachev, P. D.; Штарк, М. Б.

doi:10.1155/2015/242158

Cited by 9 publications

(8 citation statements)

References 81 publications

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“…Indeed, GA directly binds E1 and inhibits the formation of E1-SUMO intermediate at the same range of concentrations here used to prevent LTP inhibition by Aβ (Fukuda et al, 2009). In addition, GA can also inhibit the SUMOylation of p53 (Fukuda et al, 2009), which is known to play a crucial role in the early phase of LTP (Pustylnyak et al, 2015) and has been shown to be involved in aging and AD (LaFerla et al, 1996; Lanni et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

Ginkgolic Acid Protects against Aβ-Induced Synaptic Dysfunction in the Hippocampus

2016

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Ginkgo leaf is the most used form of supplement for cognitive ailments. The standardized extract formulation EGb 761 is a dietary supplement with proven benefit in several neurological and psychiatric conditions including memory decline in Alzheimer’s disease, schizophrenia and dementia. Ginkgolic acid (GA) is a component of this extract which shows pleiotropic effects including antitumoral and anti-HIV action; however, its effect on memory is still unknown. Here, we carried out an electrophysiological analysis to investigate the effects of GA on long term potentiation and synaptic transmission at CA1 hippocampal synapses. We also evaluated the potential rescuing effect of GA on the synaptic dysfunction following in vitro application of Aβ. Data obtained indicate that GA exerts neuroprotective effects against Aβ-induced impairment of neurotransmitter release and synaptic plasticity.

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Section: Discussionmentioning

confidence: 99%

Ginkgolic Acid Protects against Aβ-Induced Synaptic Dysfunction in the Hippocampus

2016

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“…The increase in p53 DNA-bound fraction was not associated with the increase in total p53 protein, which suggests p53 activation was due to post-translational modifications. The total p53 protein level even decreased in the area CA1 20 min after LTP induction, while p53 mRNA level did not change [60]. Therefore, the p53 protein degradation accelerated or/and p53 mRNA translation slowed in the early phase of LTP.…”

Section: Ltp-associated Expression Of S100b and Other P53 Target Genementioning

confidence: 88%

“…We used chromatin immunoprecipitation to study р53 binding to three loci in S100B promoter with pREs within them (Figure 1). The p53 binding to all these sites in S100B promoter strongly correlated with S100B mRNA dynamics in a time window 10-40 min after SC tetanization [60]. Interestingly, the p53 binding to the conserved site was most expressed.…”

Section: Ltp-associated Expression Of S100b and Other P53 Target Genementioning

confidence: 92%

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Long-Term Potentiation-Associated Gene Expression: Involvement of the Tumour Protein p53

Lisachev¹,

Штарк²

2018

The Hippocampus - Plasticity and Functions

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Long-term potentiation of synaptic transmission (LTP) is one of the most studied manifestations of neuroplasticity and hippocampus is a classic object for the study of LTP mechanisms. The early phase of LTP depends on modifications of pre-existing synaptic proteins and the late phase of LTP needs de novo protein synthesis and gene expression. LTP-associated dynamics of the transcriptome and mechanisms of coupling synaptic activity with gene expression are intensively studied, but due to the vast complexity of the issue, abundance of unresolved questions remains in this field. The diversity of brain cell types is one of the main challenges. Until relatively recently, the analysis of molecular and genetic aspects of neuroplasticity has usually been confined to neuronal populations. Meanwhile, glia substantially contributes to synaptic transmission regulation. Astrocytes release various gliotransmitters, which modulate synaptic transmission and plasticity. S100B is one of those glia-derived regulatory factors. Learning in rats is accompanied by an increase in S100B expression in various brain regions including the hippocampus. The present study is focused on the neuroplasticity-associated S100B expression upregulation using long-term post-tetanic potentiation in rat hippocampal slices. In this chapter, we present a short review of published articles devoted to the analysis of gene expression during LTP formation including studies of the mechanism of LTP-associated S100B upregulation in hippocampus.

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“…This Mdm2-p53-Akt signaling represents a unique pathway for Gp1 mGluRdependent plasticity mechanisms. Mdm2-p53 signaling had not been shown to regulate neuronal plasticity until recently (Jewett et al, 2015(Jewett et al, , 2016Lisachev et al, 2015;Pustylnyak et al, 2015), and still little is known about p53 signaling in the central nervous system. Our current study introduces a novel function of p53 in the regulation of activity-dependent neural network plasticity.…”

Section: Introductionmentioning

confidence: 99%

Chronic Activation of Gp1 mGluRs Leads to Distinct Refinement of Neural Network Activity through Non-Canonical p53 and Akt Signaling

Liu

Soriano

Yook

et al. 2020

eNeuro

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Group 1 metabotropic glutamate receptors (Gp1 mGluRs), including mGluR1 and mGluR5, are critical regulators for neuronal and synaptic plasticity. Dysregulated Gp1 mGluR signaling is observed with various neurologic disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, and autism spectrum disorders (ASDs). It is well established that acute activation of Gp1 mGluRs leads to elevation of neuronal intrinsic excitability and long-term synaptic depression. However, it remains unknown how chronic activation of Gp1 mGluRs can affect neural activity and what molecular mechanisms might be involved. In the current study, we employed a multielectrode array (MEA) recording system to evaluate neural network activity of primary mouse cortical neuron cultures. We demonstrated that chronic activation of Gp1 mGluRs leads to elevation of spontaneous spike frequency while burst activity and cross-electrode synchronization are maintained at the baseline. We further showed that these neural network properties are achieved through proteasomal degradation of Akt that is dependent on the tumor suppressor p53. Genetically knocking down p53 disrupts the elevation of spontaneous spike frequency and alters the burst activity and cross-electrode synchronization following chronic activation of Gp1 mGluRs. Importantly, these deficits can be restored by pharmacologically inhibiting Akt to mimic inactivation of Akt mediated by p53. Together, our findings reveal the effects of chronic activation of Gp1 mGluRs on neural network activity and identify a unique signaling pathway involving p53 and Akt for these effects. Our data can provide insights into constitutively active Gp1 mGluR signaling observed in many neurologic and psychiatric disorders. Significance Statement Group 1 metabotropic glutamate receptors (Gp1 mGluRs) are critical effectors of neuroplasticity and essential for neurodevelopment and cognition. Constitutively active Gp1 mGluR signaling has been observed in many pathologic conditions but the effects of chronic activation of Gp1 mGluRs on neuroplasticity are largely unknown. Our study provides evidence to demonstrate that chronic activation of Gp1 mGluRs refines the neural network properties through p53-dependent inactivation of Akt. These findings uncover an unconventional signaling pathway underlying Gp1 mGluR-dependent neuroplasticity and suggest distinct effects following versus chronic activation of Gp1 mGluRs.

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Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

Cited by 9 publications

References 81 publications

Ginkgolic Acid Protects against Aβ-Induced Synaptic Dysfunction in the Hippocampus

Ginkgolic Acid Protects against Aβ-Induced Synaptic Dysfunction in the Hippocampus

Long-Term Potentiation-Associated Gene Expression: Involvement of the Tumour Protein p53

Chronic Activation of Gp1 mGluRs Leads to Distinct Refinement of Neural Network Activity through Non-Canonical p53 and Akt Signaling

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