Ischemic insults promote epigenetic reprogramming of μ opioid receptor expression in hippocampal neurons

Formisano, Luigi; Noh, Kyung Min; Miyawaki, Takahiro; Mashiko, Toshihiro; Bennett, Michael V. L.; Zukin, R. Suzanne

doi:10.1073/pnas.0611704104

Cited by 123 publications

(112 citation statements)

References 53 publications

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“…MOR-1 is a member of the G protein-coupled receptor superfamily and is activated by endogenous opioid peptides (Kieffer and Gaveriaux-Ruff, 2002). In rats subjected to global ischemia, MOR-1 is downregulated in the hippocampal CA1 (Formisano et al, 2007). Ischemia promoted REST binding to the MOR-1 promoter by 12 h after ischemia, assessed by ChIP, consistent with the possibility that REST mediates MOR-1 downregulation.…”

Section: Histone Modifications and Transcriptional Regulation In Strokesupporting

confidence: 48%

“…In mature neurons REST is quiescent, but can be activated in selectively vulnerable hippocampal neurons by insults such as global ischemia (Calderone et al, 2003;Formisano et al, 2007;Noh et al, 2012) and epileptic seizures (Palm et al, 1998;Garriga-Canut et al, 2006;Gillies et al, 2009) and aberrantly accumulates in the nucleus of selectively vulnerable striatal neurons in Huntington's disease (Zuccato et al, 2003(Zuccato et al, , 2007.…”

Section: Transcriptional Regulation By Rest During Strokementioning

confidence: 99%

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Epigenetic Mechanisms in Stroke and Epilepsy

Hwang

Aromolaran

Zukin

2012

Neuropsychopharmacol

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Epigenetic remodeling and modifications of chromatin structure by DNA methylation and histone modifications represent central mechanisms for the regulation of neuronal gene expression during brain development, higher-order processing, and memory formation. Emerging evidence implicates epigenetic modifications not only in normal brain function, but also in neuropsychiatric disorders. This review focuses on recent findings that disruption of chromatin modifications have a major role in the neurodegeneration associated with ischemic stroke and epilepsy. Although these disorders differ in their underlying causes and pathophysiology, they share a common feature, in that each disorder activates the gene silencing transcription factor REST (repressor element 1 silencing transcription factor), which orchestrates epigenetic remodeling of a subset of 'transcriptionally responsive targets' implicated in neuronal death. Although ischemic insults activate REST in selectively vulnerable neurons in the hippocampal CA1, seizures activate REST in CA3 neurons destined to die. Profiling the array of genes that are epigenetically dysregulated in response to neuronal insults is likely to advance our understanding of the mechanisms underlying the pathophysiology of these disorders and may lead to the identification of novel therapeutic strategies for the amelioration of these serious human conditions.

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Section: Histone Modifications and Transcriptional Regulation In Strokesupporting

confidence: 48%

Section: Transcriptional Regulation By Rest During Strokementioning

confidence: 99%

Epigenetic Mechanisms in Stroke and Epilepsy

Hwang

Aromolaran

Zukin

2012

Neuropsychopharmacol

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“…Regulation of global gene silencing after stroke is mediated at least in part by the transcription factor repressor element silencing 1 transcription factor (REST), a potential candidate for orchestrating epigenetic modifications in postischemic neurons. [79][80][81] REST is activated after neuronal damage and its de-repression leads to the repression of many neuronal genes involved in synaptic plasticity and remodeling. REST silences target genes via association with distinct corepressor elements, which in turn recruit HDACs 1 and 2, but also associate with the transcriptional repressor methyl-CpG binding protein 2 (MeCP2), as well as the repressive histone methyltransferase G9a.…”

Section: Epigenetic Mechanisms S Schweizer Et Almentioning

confidence: 99%

Epigenetic Mechanisms in Cerebral Ischemia

Schweizer

Meisel

Märschenz

2013

J Cereb Blood Flow Metab

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Treatment efficacy for ischemic stroke represents a major challenge. Despite fundamental advances in the understanding of stroke etiology, therapeutic options to improve functional recovery remain limited. However, growing knowledge in the field of epigenetics has dramatically changed our understanding of gene regulation in the last few decades. According to the knowledge gained from animal models, the manipulation of epigenetic players emerges as a highly promising possibility to target diverse neurologic pathologies, including ischemia. By altering transcriptional regulation, epigenetic modifiers can exert influence on all known pathways involved in the complex course of ischemic disease development. Beneficial transcriptional effects range from attenuation of cell death, suppression of inflammatory processes, and enhanced blood flow, to the stimulation of repair mechanisms and increased plasticity. Most striking are the results obtained from pharmacological inhibition of histone deacetylation in animal models of stroke. Multiple studies suggest high remedial qualities even upon late administration of histone deacetylase inhibitors (HDACi). In this review, the role of epigenetic mechanisms, including histone modifications as well as DNA methylation, is discussed in the context of known ischemic pathways of damage, protection, and regeneration.

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“…AS-ODN-induced regulation of many different types of proteins, including receptors (Wahlestedt et al, 1993;Pizzi et al, 1999;Kumar et al, 2001;Alessandri-Haber et al, 2003), transcription factors (Sugiyo et al, 2001), neuropeptides and neurotransmitters (Spampinato et al, 1994), and growth factors (Kitajima et al, 1999), has helped neurobiologists to understand certain physiological or pathological processes in a specific neural functions. Recently, AS-ODN has been used to explore the molecular events or signal pathways induced by functional gene expression in neuronal development (Formisano et al, 2007;Huh et al, 2008;Li et al, 2008). We also used AS-ODN in vivo to explore the molecular mechanisms of nNOS in motoneuron death (Zhou and Wu, 2006).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of the neuronal nitric oxide synthase gene retard the development of the cerebellar granule neurons in vitro

Wang

Peng

et al. 2010

Developmental Dynamics

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The role of endogenous neuronal nitric oxide synthase (nNOS) gene in the development of cerebellar granule neurons (CGNs) is conflicting. Here, we tested the effect of antisense oligos (AS-ODN) on the endogenous nNOS gene and the development of the CGNs in vitro. The expression of nNOS increased in a development-dependent pattern both in terms of mRNA and protein. AS-ODN down-regulated nNOS gene, but in a posttranscriptional manner. Knockdown of nNOS protein decreased the viability of the CGNs from 7 to 13 days in culture (DIC). This activity of AS-ODN was mimicked by nNOS inhibitor I. The antagonist (nNOSi, MK-801, or ODQ) -induced decrease of cell viability was normalized by the provision of the sodium nitroprusside, an NO donor. This study provides direct evidence that endogenous nNOS, mainly by means of its principal product NO, plays an active role in sustaining the survival of developing CGNs at transition from differentiation to maturation. Developmental Dynamics 239:474-481,

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Ischemic insults promote epigenetic reprogramming of μ opioid receptor expression in hippocampal neurons

Abstract: Transient global ischemia is a neuronal insult that induces delayed

Cited by 123 publications

References 53 publications

Epigenetic Mechanisms in Stroke and Epilepsy

Epigenetic Mechanisms in Stroke and Epilepsy

Epigenetic Mechanisms in Cerebral Ischemia

Knockdown of the neuronal nitric oxide synthase gene retard the development of the cerebellar granule neurons in vitro

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