ΔFosB in brain reward circuits mediates resilience to stress and antidepressant responses

Vialou, Vincent; Robison, Alfred J.; LaPlant, Quincey; Covington, Herbert E.; Dietz, David M.; Mouzon, Ezekiell; Rush, A. John; Watts, Emily L.; Wallace, Deanna L.; Iñiguez, Sergio D.; Ohnishi, Yoshinori N.; Steiner, Michel; Warren, Brandon L.; Krishnan, Vaishnav; Bolaños, Carlos A.; Neve, Rachael L.; Ghose, Subroto; Berton, Olivier; Tamminga, Carol A.; Nestler, Eric J.

doi:10.1038/nn.2551

Cited by 443 publications

(471 citation statements)

References 51 publications

Supporting

Mentioning

436

Contrasting

Unclassified

Order By: Relevance

“…AMPA receptors mediate the majority of fast excitatory synaptic transmission in the CNS, and disrupted AMPA receptor function is thought to be involved in learning and memory abnormalities, 17 addiction, 18 and depression, 19 among other disorders. Anti-AMPA receptor autoantibodies bind the receptor, leading to a reversible internalization and removal from the synapse.…”

Section: Autoimmune Synaptic Encephalitismentioning

confidence: 99%

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

Kayser¹,

Dalmau²

2011

Journal of Neuropsychiatry

115

View full text Add to dashboard Cite

show abstract

Section: Autoimmune Synaptic Encephalitismentioning

confidence: 99%

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

Kayser¹,

Dalmau²

2011

Journal of Neuropsychiatry

115

View full text Add to dashboard Cite

show abstract

“…The elucidation of endogenous mechanisms underlying resilience to chronic stress should shed light on developing the therapeutic strategies for major depression (Zhu et al, 2017). Although a few of molecules are presumably involved in major depression versus resilience (Bergstrom, Jayatissa, Thykjaer, & Wiborg, 2007; Christensen, Bisgaard, & Wiborg, 2011; Friedman et al, 2014; Manji et al, 2003; Vialou et al, 2010; Wang, Perova, Arenkiel, & Li, 2014). However, comprehensive molecular profiles in specific brain areas remain to be systemically figured in terms of resilience and susceptibility to chronic stress for major depression.…”

Section: Introductionmentioning

confidence: 99%

microRNA and mRNA profiles in nucleus accumbens underlying depression versus resilience in response to chronic stress

Song

Sun

et al. 2018

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Major depression in negative mood is presumably induced by chronic stress with lack of reward. However, most individuals who experience chronic stress demonstrate resilience. Molecular mechanisms underlying stress‐ induced depression versus resilience remain unknown, which are investigated in brain reward circuits. Mice were treated by chronic unpredictable mild stress (CUMS) for 4 weeks. The tests of sucrose preference, Y‐maze, and forced swimming were used to identify depression‐like emotion behavior or resilience. High‐throughput sequencing was used to analyze mRNA and miRNA quantity in the nucleus accumbens (NAc) harvested from the mice in the groups of control, CUMS‐induced depression (CUMS‐MDD), and CUMS‐resistance to identify molecular profiles of CUMS‐MDD versus CUMS‐resilience. In data analyses and comparison among three groups, 1.5‐fold ratio in reads per kilo‐base per million reads (RPKM) was set to judge involvements of mRNA and miRNA in CUMS, MDD, or resilience. The downregulations of serotonergic/dopaminergic synapses, MAPK/calcium signaling pathways, and morphine addiction as well as the upregulations of cAMP/PI3K‐Akt signaling pathways and amino acid metabolism are associated with CUMS‐MDD. The downregulations of chemokine signaling pathway, synaptic vesicle cycle, and nicotine addiction as well as the upregulations of calcium signaling pathway and tyrosine metabolism are associated with CUMS‐resilience. The impairments of serotonergic/dopaminergic synapses and PI3K‐Akt/MAPK signaling pathways in the NAc are associated with depression. The upregulation of these entities is associated with resilience. Consistent results from analyzing mRNA/miRNA and using different methods validate our finding and conclusion.

show abstract

“…This subcortical nuclei of the ventral striatum mediates neural communication between cortical regions and the limbic system in order to regulate emotion and cognition. The NAc acts as a central regulator of emotional behaviors, and its function is tightly modulated by a number of molecular mechanisms, including histone deactylases, IkK, and DFosB, among others (Christoffel et al, 2011a;Covington et al, 2009;Vialou et al, 2010). Importantly, the NAc is a relevant target for therapeutic exploration in major depressive disorder, as deep brain stimulation of the NAc reduces anxiety and depression in previously treatment-resistant major depressive disorder patients (Bewernick et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Effects of Inhibitor of κB Kinase Activity in the Nucleus Accumbens on Emotional Behavior

Christoffel

Golden

Heshmati

et al. 2012

Neuropsychopharmacol

Self Cite

View full text Add to dashboard Cite

Inhibitor of kB kinase (IkK) has historically been studied in the context of immune response and inflammation, but recent evidence demonstrates that IkK activity is necessary and sufficient for regulation of neuronal function. Chronic social defeat stress of mice increases IkK activity in the nucleus accumbens (NAc) and this increase is strongly correlated to depression-like behaviors. Inhibition of IkK signaling results in a reversal of chronic social defeat stress-induced social avoidance behavior. Here, we more completely define the role of IkK in anxiety and depressive-like behaviors. Mice underwent stereotaxic microinjection of a herpes simplex virus expressing either green fluorescent protein, a constitutively active form of IkK (IkKca), or a dominant negative form of IkK into the NAc. Of all three experimental groups, only mice expressing IkKca show a behavioral phenotype. Expression of IkKca results in a decrease in the time spent in the nonperiphery zones of an open field arena and increased time spent immobile during a forced swim test. No baseline differences in sucrose preference were observed, but following the acute swim stress we noted a marked reduction in sucrose preference. To determine whether IkK activity alters responses to other acute stressors, we examined behavior and spine morphology in mice undergoing an acute social defeat stress. We found that IkKca enhanced social avoidance behavior and promoted thin spine formation. These data show that IkK in NAc is a critical regulator of both depressive-and anxiety-like states and may do so by promoting the formation of immature excitatory synapses.

show abstract

ΔFosB in brain reward circuits mediates resilience to stress and antidepressant responses

Cited by 443 publications

References 51 publications

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

microRNA and mRNA profiles in nucleus accumbens underlying depression versus resilience in response to chronic stress

Effects of Inhibitor of κB Kinase Activity in the Nucleus Accumbens on Emotional Behavior

Contact Info

Product

Resources

About