The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum

Piechota, Marcin; Korostyński, Michał; Solecki, Wojciech; Gieryk, Agnieszka; Ślęzak, Michał; Bilecki, Wiktor; Ziółkowska, Barbara; Kostrzewa, Elzbieta; Cymerman, Iwona A.; Swiech, Lukasz; Jaworski, Jacek; Przewłocki, Ryszard

doi:10.1186/gb-2010-11-5-r48

Cited by 139 publications

(169 citation statements)

References 110 publications

Supporting

Mentioning

157

Contrasting

Order By: Relevance

“…Finally, we determine that srf and actin, which bear SRE sites in their promoter, are not regulated by an acute cocaine administration. Our demonstration of an involvement of Elk-1 activation in cocaine-induced SRE-driven gene regulations is strengthened by a recent whole-genome microarray profiling of drugs of abuse showing that one important cluster of upregulated genes is under the control of SRF/SRE regulatory sites (Piechota et al, 2010). Induction of this group of genes was strongly impaired by SL327 pretreatment, thus showing the involvement of ERK signaling in the instatement of a large group of genes in response to cocaine.…”

Section: Discussionmentioning

confidence: 61%

Alterations of Molecular and Behavioral Responses to Cocaine by Selective Inhibition of Elk-1 Phosphorylation

Besnard¹,

Bouveyron²,

Kappès³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

Activation of the extracellular signal-regulated kinase (ERK) signaling pathway in the striatum is crucial for molecular adaptations and long-term behavioral alterations induced by cocaine. In response to cocaine, ERK controls the phosphorylation levels of both mitogen and stress-activated protein kinase 1 (MSK-1), a nuclear kinase involved in histone H3 (Ser10) and cAMP response element binding protein phosphorylation, and Elk-1, a transcription factor involved in serum response element (SRE)-driven gene regulations. We recently characterized the phenotype of msk-1 knock-out mice in response to cocaine. Herein, we wanted to address the role of Elk-1 phosphorylation in cocaine-induced molecular, morphological, and behavioral responses. We used a cell-penetrating peptide, named TAT-DEF-Elk-1 (TDE), which corresponds to the DEF docking domain of Elk-1 toward ERK and inhibits Elk-1 phosphorylation induced by ERKs without modifying ERK or MSK-1 in vitro. The peptide was injected in vivo before cocaine administration in mice. Immunocytochemical, molecular, morphological, and behavioral studies were performed. The TDE inhibited Elk-1 and H3 (Ser10) phosphorylation induced by cocaine, sparing ERK and MSK-1 activation. Consequently, TDE altered cocaine-induced regulation of genes bearing SRE site(s) in their promoters, including c-fos, zif268, ⌬FosB, and arc/arg3.1 (activity-regulated cytoskeleton-associated protein). In a chronic cocaine administration paradigm, TDE reversed cocaine-induced increase in dendritic spine density. Finally, the TDE delayed the establishment of cocaine-induced psychomotor sensitization and conditioned-place preference. We conclude that Elk-1 phosphorylation downstream from ERK is a key molecular event involved in long-term neuronal and behavioral adaptations to cocaine.

show abstract

Section: Discussionmentioning

confidence: 61%

Alterations of Molecular and Behavioral Responses to Cocaine by Selective Inhibition of Elk-1 Phosphorylation

Besnard¹,

Bouveyron²,

Kappès³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The results of our analysis offer insights into the relationship between psychostimulant exposure and neuroinflammation. Piechota et al (2010) studied the time course of gene expression changes in the striatum of adult C57BL/6J mice following administration of a variety of drugs (nicotine, ethanol, cocaine, morphine, heroin, and methamphetamine), at 1, 2, 4, and 8 h after exposure. At 1 h after administration of cocaine (25 mg/kg), gene arrays showed statistically significant (p \ 0.01) increases in the following: hypoxia inducible factor-1 (HIF-1), multiple transcription factors (EGR2, EGR3, EGR4), astrocyte growth factor/mitogen Amphiregulin (Areg), cytokine receptors (IL-6r, TNF-a), TLR13, and MMP16.…”

Section: Evidence Of a Neuroinflammatory Response In Psychostimulant mentioning

confidence: 99%

“…Asanuma et al (2004) provided an early report of microglial activation by relatively high dose amphetamine in mice (four treatments of 4 mg/kg at 2-h intervals). To add to an understanding of psychostimulantassociated changes in IIR gene expression, we performed post hoc analysis on the annotated datasets from three experiments (Piechota et al 2010;Renthal et al 2007;Ahmed et al 2005) which are available in the GEO public database. Using a two-tailed T test (p \ 0.01) within GEO, we compared the cocaine-and/or methamphetamine-treated animals to saline controls, searching for changes in expression of inflammatory-related transcripts in response to drug.…”

Section: Evidence Of a Neuroinflammatory Response In Psychostimulant mentioning

confidence: 99%

Psychostimulant Abuse and Neuroinflammation: Emerging Evidence of Their Interconnection

2012

View full text Add to dashboard Cite

During the past two decades, there has been a tremendous expansion of knowledge regarding the neurobiological effects of substance abuse and how these effects impact behavior. At the same time, there has been a profound change in our understanding of the way in which the central nervous system responds to noxious stimuli. Most often referred to as the innate immune response (IIR), this defense mechanism is activated by a number of agents (toxic, microbial, ischemic) and has been implicated in the progression of a number of neurodegenerative diseases. We review evidence that psychostimulants of abuse (cocaine, methamphetamine, ecstasy) are associated with activation of the IIR. We first present background on what is currently known about the IIR including some of the cellular elements involved (microglia, astrocytes, vascular endothelial cells), key receptor pathways, and primary inflammatory cytokines (IL-1β, IL-6, TNF-α). We then present a variety of protein and gene expression data taken from animal studies that show increased expression of various components of the IIR following acute or repeated psychostimulant administration. Collectively the data indicate an association of psychostimulant use with IIR activation in the brain even at exposures not traditionally associated with neurotoxicity. Thus, the gradually escalating deleterious effects of psychostimulant use could in part involve neuroinflammatory mechanisms. Finally, we offer one hypothesis of a possible mechanism by which psychostimulants result in IIR activation and discuss the potential therapeutic implications of these findings for treatment of the recovering addict.

show abstract

“…The expression of hypoxanthine guanine phosphoribosyl transferase 1 (Hprt1 -Mm03024075_m1), which had a stable mRNA level, was quantified to control for variations in cDNA amounts. The usefulness of Hprt1 as a reference transcript was determined in our previous studies (Korostynski et al 2007;Piechota et al 2010).…”

Section: Contingent Versus Non-contingent Administration Of Chocolatementioning

confidence: 99%

New operant model of reinstatement of food-seeking behavior in mice

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum

Abstract: The transcriptional response to six commonly-abused drugs was assessed in the mouse brain revealing common modules of drug-induced genes.

Cited by 139 publications

References 110 publications

Alterations of Molecular and Behavioral Responses to Cocaine by Selective Inhibition of Elk-1 Phosphorylation

Alterations of Molecular and Behavioral Responses to Cocaine by Selective Inhibition of Elk-1 Phosphorylation

Psychostimulant Abuse and Neuroinflammation: Emerging Evidence of Their Interconnection

New operant model of reinstatement of food-seeking behavior in mice

Contact Info

Product

Resources

About