Regulation of Opioid Gene Expression: A Model To Understand Neural Plasticity

Comb, Michael J.; Kobierski, Linda A.; Chu, Hung-Ming; Tan, Yi; Borsook, David; Herrup, Karl; Hyman, Steven E.

doi:10.1037/e496112006-011

Cited by 12 publications

(10 citation statements)

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“…ENK encodes various enkephalin peptides that act as neurotransmitters in the CNS. ENK consists of three exons separated by two introns, the precursor protein proenkephalin is encoded by exon III (Comb et al,1992). From this precursor protein, proteolytic cleavage generates four copies of met‐enkephalin and one copy of leu‐enkephalin as well as several enkephalin‐like molecules.…”

Section: Discussionmentioning

confidence: 99%

Evidence for disease‐regulated transgene expression in the brain with use of lentiviral vectors

Jakobsson

Rosenqvist

Mårild

et al. 2006

J of Neuroscience Research

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In this study we have developed and validated a novel approach of transgene regulation in the brain. By using lentiviral vectors that incorporate promoters of genes that are up-regulated during different pathological states, we were able to regulate transgene expression in accordance with the disease process. When using a glial fibrillary acidic protein promoter, efficient disease regulation in glial cells was achieved after an excitotoxic lesion or a 6-hydroxydopamine (6-OHDA) lesion. Transgene expression was physiologically regulated and displayed a dose-dependent increase depending on the severity of lesion. Efficient regulation was also achieved in neurons when using a preproenkephlin promoter in 6-OHDA-lesioned rats, allowing combined regulation and targeting. This disease-regulated approach allows control of transgene expression in the brain without the use of inducer molecules and without overexpression of transactivator proteins.

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Section: Discussionmentioning

confidence: 99%

Evidence for disease‐regulated transgene expression in the brain with use of lentiviral vectors

Jakobsson

Rosenqvist

Mårild

et al. 2006

J of Neuroscience Research

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“…jneurosci.org as supplemental material) are potential Egr1 targets, which may mediate its effects on neuronal activity. Some of them, such as Junb, Nrgn, Prnp, Rac1, and Syn2, have been implicated in neuronal plasticity by previous studies (Comb et al, 1992;Huang et al, 2004;Tashiro and Yuste, 2004;Papassotiropoulos et al, 2005;Sun et al, 2006). We further characterized one of the genes with expression highly correlated with Egr1, neurogranin (Nrgn).…”

Section: The Immediate Early Gene Egr1 Is Implicated In Neuronal Plmentioning

confidence: 91%

Transcriptional Signatures of Cellular Plasticity in Mice Lacking the α1 Subunit of GABA_AReceptors

et al. 2006

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GABA A receptors mediate the majority of inhibitory neurotransmission in the CNS. Genetic deletion of the ␣1 subunit of GABA A receptors results in a loss of ␣1-mediated fast inhibitory currents and a marked reduction in density of GABA A receptors. A grossly normal phenotype of ␣1-deficient mice suggests the presence of neuronal adaptation to these drastic changes at the GABA synapse. We used cDNA microarrays to identify transcriptional fingerprints of cellular plasticity in response to altered GABAergic inhibition in the cerebral cortex and cerebellum of ␣1 mutants. In silico analysis of 982 mutation-regulated transcripts highlighted genes and functional groups involved in regulation of neuronal excitability and synaptic transmission, suggesting an adaptive response of the brain to an altered inhibitory tone. Public gene expression databases permitted identification of subsets of transcripts enriched in excitatory and inhibitory neurons as well as some glial cells, providing evidence for cellular plasticity in individual cell types. Additional analysis linked some transcriptional changes to cellular phenotypes observed in the knock-out mice and suggested several genes, such as the early growth response 1 (Egr1), small GTP binding protein Rac1 (Rac1), neurogranin (Nrgn), sodium channel ␤4 subunit (Scn4b), and potassium voltage-gated Kv4.2 channel (Kcnd2) as cell type-specific markers of neuronal plasticity. Furthermore, transcriptional activation of genes enriched in Bergman glia suggests an active role of these astrocytes in synaptic plasticity. Overall, our results suggest that the loss of ␣1-mediated fast inhibition produces diverse transcriptional responses that act to regulate neuronal excitability of individual neurons and stabilize neuronal networks, which may account for the lack of severe abnormalities in ␣1 null mutants.

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“…A generally accepted hypothesis for the development of opioid addiction is that chronic opioid exposure leads to altered gene expression that results in neuroadaptations that are eventually linked to addictive behavioral changes [1]. Thus, a better understanding of the molecular mechanisms of chronic opioid-induced gene expression will provide us insights into how opioid tolerance and addiction develop and may eventually provide new molecular targets for the prevention and treatment of opioid tolerance and dependence.…”

Section: Introductionmentioning

confidence: 99%

Mu-opioid signaling modulates biphasic expression of TrkB and IκBα genes and neurite outgrowth in differentiating and differentiated human neuroblastoma cells

Wen

Guo

Chen

2013

Biochemical and Biophysical Research Communications

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Chronic opioid exposure leads to changes in gene expression (functional changes), resulting in structural changes in neural circuits that are linked to eventually behavioral changes. Little is known about the cellular and molecular mechanisms of how such changes occur. In this study, we found that mu-opioid [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) and morphine exposure led to dynamic changes in neural differentiation- and growth-associated genes, IκBα and NTRK2 (TrkB), in differentiating and differentiated human neuroblastoma SH-SY5Y cells. Chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) analysis revealed that binding of NF-κB/p65 to the IκBα promoter in living cells was temporally altered when the cells were exposed to morphine. The changes in gene expression correlated with the changes in neurite length of the RA-differentiating and RA-differentiated neuron-like cells. Our findings for the first time showed that TrkB signaling and NF-κB/IκBα signaling temporally correlated with each other in response to single-dose and repeated mu-opioid treatment in differentiating and differentiated human neuron-like cells. The findings from this human cell study in vitro indicate that both relatively high single-dose and chronic opioid exposure may induce the structural changes in the developing human brain and the adult brain by altering the expression of neuronal differentiation- and neurite outgrowth-related genes IκBa and TrkB in vivo.

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Regulation of Opioid Gene Expression: A Model To Understand Neural Plasticity

Cited by 12 publications

References 0 publications

Evidence for disease‐regulated transgene expression in the brain with use of lentiviral vectors

Evidence for disease‐regulated transgene expression in the brain with use of lentiviral vectors

Transcriptional Signatures of Cellular Plasticity in Mice Lacking the α1 Subunit of GABA_AReceptors

Mu-opioid signaling modulates biphasic expression of TrkB and IκBα genes and neurite outgrowth in differentiating and differentiated human neuroblastoma cells

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Regulation of Opioid Gene Expression: A Model To Understand Neural Plasticity

Cited by 12 publications

References 0 publications

Evidence for disease‐regulated transgene expression in the brain with use of lentiviral vectors

Evidence for disease‐regulated transgene expression in the brain with use of lentiviral vectors

Transcriptional Signatures of Cellular Plasticity in Mice Lacking the α1 Subunit of GABAAReceptors

Mu-opioid signaling modulates biphasic expression of TrkB and IκBα genes and neurite outgrowth in differentiating and differentiated human neuroblastoma cells

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Transcriptional Signatures of Cellular Plasticity in Mice Lacking the α1 Subunit of GABA_AReceptors