Activity-Regulated Cytoskeleton-Associated Protein Accumulates in the Nucleus in Response to Cocaine and Acts as a Brake on Chromatin Remodeling and Long-Term Behavioral Alterations

Salery, Marine; Santos, Marc Dos; Saint-Jour, Estefani; Moumné, Lara; Pagès, Christiane; Kappès, Vincent; Parnaudeau, Sébastien; Caboche, Jocelyne; Vanhoutte, Peter

doi:10.1016/j.biopsych.2016.05.025

Cited by 47 publications

(50 citation statements)

References 51 publications

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“…Our observations here reveal reliable anxiolytic-like effects in Arc KO mice across three different behavioral tests. While previous reports using the same strain of Arc KO mice have noted significant decreases 60 and increases 58 in locomotion, we observe no significant differences in Arc KO mouse activity in a locomotor assay ( Figure 1D-F). Arc KO mice also did not show increased activity in the social novelty assay (Figure 2B,D).…”

Section: Discussioncontrasting

confidence: 99%

Activity‐regulated cytoskeleton‐associated protein (Arc/Arg3.1) regulates anxiety‐ and novelty‐related behaviors

Penrod

Kumar

Smith

et al. 2019

Genes Brain and Behavior

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The activity-regulated cytoskeleton-associated protein (Arc, also known as Arg3.1) regulates glutamatergic synapse plasticity and has been linked to neuropsychiatric illness; however, its role in behaviors associated with mood and anxiety disorders remains unclear. We find that stress upregulates Arc expression in the adult mouse nucleus accumbens (NAc) – a brain region implicated in mood and anxiety behaviors. Global Arc knockout mice have altered AMPAR-subunit surface levels in the adult NAc, and the Arc-deficient mice show reductions in anxiety-like behavior, deficits in social novelty preference, and anti-depressive-like behavior. Viral-mediated expression of Arc in the adult NAc of male, global Arc KO mice restores normal levels of anxiety-like behavior in the elevated plus maze. Consistent with this finding, viral-mediated reduction of Arc in the adult NAc reduces anxiety-like behavior in male, but not female, mice in the elevated plus maze. NAc-specific reduction of Arc also produced significant deficits in both object and social novelty preference tasks. Together our findings indicate that Arc is essential for regulating normal mood-and anxiety-related behaviors and novelty discrimination, and that Arc’s function within the adult NAc contributes to these behavioral effects.

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Section: Discussioncontrasting

confidence: 99%

Activity‐regulated cytoskeleton‐associated protein (Arc/Arg3.1) regulates anxiety‐ and novelty‐related behaviors

Penrod

Kumar

Smith

et al. 2019

Genes Brain and Behavior

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“…Increased Arc/Arg3.1 levels were preferentially found in the D1R-expressing SPNs located in striosome compartments. These results extend earlier studies showing that acute psychostimulant administration upregulates Arc/Arg3.1 transcripts and protein levels in the striatum (Fosnaugh et al, 1995; Tan et al, 2000; Klebaur et al, 2002; Fumagalli et al, 2006; Salery et al, 2016). While Arc/Arg3.1 expression is often used as a marker of neuronal activity, convergent evidence suggests that the induction of this plasticity-associated gene would sustain homeostatic responses.…”

Section: Discussionsupporting

confidence: 90%

Repeated Exposure to D-Amphetamine Decreases Global Protein Synthesis and Regulates the Translation of a Subset of mRNAs in the Striatum

Biever

Boubaker-Vitre

Cutando

et al. 2017

Front. Mol. Neurosci.

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Repeated psychostimulant exposure induces persistent gene expression modifications that contribute to enduring changes in striatal GABAergic spiny projecting neurons (SPNs). However, it remains unclear whether changes in the control of mRNA translation are required for the establishment of these durable modifications. Here we report that repeated exposure to D-amphetamine decreases global striatal mRNA translation. This effect is paralleled by an enhanced phosphorylation of the translation factors, eIF2α and eEF2, and by the concomitant increased translation of a subset of mRNAs, among which the mRNA encoding for the activity regulated cytoskeleton-associated protein, also known as activity regulated gene 3.1 (Arc/Arg3.1). The enrichment of Arc/Arg3.1 mRNA in the polysomal fraction is accompanied by a robust increase of Arc/Arg3.1 protein levels within the striatum. Immunofluorescence analysis revealed that this increase occurred preferentially in D1R-expressing SPNs localized in striosome compartments. Our results suggest that the decreased global protein synthesis following repeated exposure to D-amphetamine favors the translation of a specific subset of mRNAs in the striatum.

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“…Overall we focus on three select IEGs that have been examined in MSN subtypes in psychostimulant action. However, examination of other psychostimulant relevant IEGs, such as Arc and CREB (Carlezon et al, 1998; Salery et al, 2017), in MSN subtypes will provide a more comprehensive understanding of IEG function in striatal neuron subtypes in psychostimulant abuse. These MSN subtype specific studies have been restricted to non-contingent behaviors or the acquisition phase of self-administration, in the case of ∆FosB.…”

Section: Resultsmentioning

confidence: 99%

Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

Chandra

Lobo

2017

Front. Behav. Neurosci.

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Immediate early genes (IEGs) were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN) subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

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Activity-Regulated Cytoskeleton-Associated Protein Accumulates in the Nucleus in Response to Cocaine and Acts as a Brake on Chromatin Remodeling and Long-Term Behavioral Alterations

Cited by 47 publications

References 51 publications

Activity‐regulated cytoskeleton‐associated protein (Arc/Arg3.1) regulates anxiety‐ and novelty‐related behaviors

Activity‐regulated cytoskeleton‐associated protein (Arc/Arg3.1) regulates anxiety‐ and novelty‐related behaviors

Repeated Exposure to D-Amphetamine Decreases Global Protein Synthesis and Regulates the Translation of a Subset of mRNAs in the Striatum

Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

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