Eric J Nestler

Icahn School of Medicine at Mount Sinai, Borough of Manhattan, New York, United States

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Publications (559)4862.01 Total impact

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    ABSTRACT: Psychiatric disorders are complex multifactorial illnesses involving chronic alterations in neural circuit structure and function as well as likely abnormalities in glial cells. While genetic factors are important in the etiology of most mental disorders, the relatively high rates of discordance among identical twins, particularly for depression and other stress-related syndromes, clearly indicate the importance of additional mechanisms. Environmental factors such as stress are known to play a role in the onset of these illnesses. Exposure to such environmental insults induces stable changes in gene expression, neural circuit function, and ultimately behavior, and these maladaptations appear distinct between developmental versus adult exposures. Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions. Indeed, transcriptional dysregulation and the aberrant epigenetic regulation that underlies this dysregulation is a unifying theme in psychiatric disorders. Here, we provide a progress report of epigenetic studies of the three major psychiatric syndromes, depression, schizophrenia, and bipolar disorder. We review the literature derived from animal models of these disorders as well as from studies of postmortem brain tissue from human patients. While epigenetic studies of mental illness remain at early stages, understanding how environmental factors recruit the epigenetic machinery within specific brain regions to cause lasting changes in disease susceptibility and pathophysiology is revealing new insight into the etiology and treatment of these conditions.
    The Neuroscientist 10/2015; DOI:10.1177/1073858415608147 · 6.84 Impact Factor
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    ABSTRACT: Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF (ATP-utilizing chromatin assembly and remodeling factor) ATP-dependent chromatin-remodeling complex, occurring in the nucleus accumbens of stress-susceptible mice and depressed humans, is necessary for stress-induced depressive-like behaviors. We found that altered ACF binding after chronic stress was correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning were associated with repressed expression of genes implicated in susceptibility to stress. Together, our findings identify the
    Nature medicine 09/2015; advance online publication(10). DOI:10.1038/nm.3939 · 27.36 Impact Factor
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    ABSTRACT: Background We examined the neurobiological mechanisms underlying stress susceptibility using structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to determine neuroanatomical differences between stress-susceptible and resilient mice. We also examined synchronized anatomical differences between brain regions to gain insight into the plasticity of neural networks underlying stress susceptibility. Methods C57/Bl6 mice underwent 10 days of social defeat stress and were subsequently tested for social avoidance. For MRI, brains of stressed (susceptible n=11, resilient n=8) and control (n=12) mice were imaged ex vivo at 56µm resolution using a T2-weighted sequence. We tested for behavior-structure correlations by regressing social avoidance z-scores against local brain volume. For DTI, brains were scanned with a diffusion-weighted fast-spin echo sequence at 78μm isotropic voxels. Structural covariance was assessed by correlating local volume between brain regions. Results Social avoidance correlated negatively with local volume of the cingulate cortex, nucleus accumbens, thalamus, raphé nuclei and bed nucleus of the stria terminals. Social avoidance correlated positively with volume of the ventral tegmental area (VTA), habenula, periaqueductal grey, cerebellum, hypothalamus, and hippocampal CA3. Fractional anisotropy (FA) was increased in the hypothalamus and hippocampal CA3. We observed synchronized anatomical differences between the VTA and cingulate cortex, the hippocampus and VTA, hippocampus and cingulate cortex, and hippocampus and hypothalamus. These correlations revealed different structural covariance between brain regions in susceptible and resilient mice. Conclusions Stress-integrative brain regions shape the neural architecture underlying individual differences in susceptibility and resilience to chronic stress.
    Biological Psychiatry 08/2015; DOI:10.1016/j.biopsych.2015.08.009 · 10.26 Impact Factor
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    ABSTRACT: The cAMP and cAMP-dependent protein kinase A (PKA) signaling cascade is a ubiquitous pathway acting downstream of multiple neuromodulators. We found that the phosphorylation of phosphodiesterase-4 (PDE4) by cyclin-dependent protein kinase 5 (Cdk5) facilitated cAMP degradation and homeostasis of cAMP/PKA signaling. In mice, loss of Cdk5 throughout the forebrain elevated cAMP levels and increased PKA activity in striatal neurons, and altered behavioral responses to acute or chronic stressors. Ventral striatum- or D1 dopamine receptor-specific conditional knockout of Cdk5, or ventral striatum infusion of a small interfering peptide that selectively targeted the regulation of PDE4 by Cdk5, produced analogous effects on stress-induced behavioral responses. Together, our results demonstrate that altering cAMP signaling in medium spiny neurons of the ventral striatum can effectively modulate stress-induced behavioral states. We propose that targeting the Cdk5 regulation of PDE4 could be a new therapeutic approach for clinical conditions associated with stress, such as depression.
    Nature Neuroscience 07/2015; 18(8). DOI:10.1038/nn.4066 · 16.10 Impact Factor
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    ABSTRACT: Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry," consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression - the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus - in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 hours following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders. Copyright © 2015. Published by Elsevier Ltd.
    Neuropharmacology 07/2015; 99. DOI:10.1016/j.neuropharm.2015.07.005 · 5.11 Impact Factor
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    Dataset: SI Neuron

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    ABSTRACT: Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation-associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity, and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near-saturating levels throughout the neuronal genome by mid-adolescence. Despite such accumulation, H3.3-containing nucleosomes remain highly dynamic-in a modification-independent manner-to control neuronal- and glial-specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical and previously undocumented regulator of cell type-specific transcription and plasticity in mammalian brain. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neuron 07/2015; 87(1):77-94. DOI:10.1016/j.neuron.2015.06.014 · 15.05 Impact Factor
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    ABSTRACT: Epigenetic mechanisms, such as histone modifications, regulate responsiveness to drugs of abuse, such as cocaine, but relatively little is known about the regulation of addictive-like behaviors by DNA methylation. To investigate the influence of DNA methylation on the locomotor-activating effects of cocaine and on drug-seeking behavior, rats receiving methyl supplementation via chronic l-methionine (MET) underwent either a sensitization regimen of intermittent cocaine injections or intravenous self-administration of cocaine, followed by cue-induced and drug-primed reinstatement. MET blocked sensitization to the locomotor-activating effects of cocaine and attenuated drug-primed reinstatement, with no effect on cue-induced reinstatement or sucrose self-administration and reinstatement. Furthermore, upregulation of DNA methyltransferase 3a and 3b and global DNA hypomethylation were observed in the nucleus accumbens core (NAc), but not in the medial prefrontal cortex (mPFC), of cocaine-pretreated rats. Glutamatergic projections from the mPFC to the NAc are critically involved in the regulation of cocaine-primed reinstatement, and activation of both brain regions is seen in human addicts when reexposed to the drug. When compared with vehicle-pretreated rats, the immediate early gene c-Fos (a marker of neuronal activation) was upregulated in the NAc and mPFC of cocaine-pretreated rats after cocaine-primed reinstatement, and chronic MET treatment blocked its induction in both regions. Cocaine-induced c-Fos expression in the NAc was associated with reduced methylation at CpG dinucleotides in the c-Fos gene promoter, effects reversed by MET treatment. Overall, these data suggest that drug-seeking behaviors are, in part, attributable to a DNA methylation-dependent process, likely occurring at specific gene loci (e.g., c-Fos) in the reward pathway. Copyright © 2015 the authors 0270-6474/15/358948-11$15.00/0.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 06/2015; 35(23):8948-58. DOI:10.1523/JNEUROSCI.5227-14.2015 · 6.34 Impact Factor
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    ABSTRACT: Repeated exposure to cocaine or social stress leads to lasting structural and functional synaptic alterations in medium spiny neurons (MSNs) of nucleus accumbens (NAc). Although cocaine-induced and stress-induced structural changes in dendritic spines have been well documented, few studies have investigated functional consequences of cocaine and stress at the level of single spines. We exposed mice to chronic cocaine or chronic social defeat stress and used two-photon laser scanning microscopy with glutamate photo-uncaging and whole-cell recording to examine synaptic strength at individual spines on two distinct types of NAc MSNs in acute slices after 24 hours of cocaine withdrawal and after chronic social defeat stress. In animals treated with cocaine, average synaptic strength was reduced specifically at large mushroom spines of MSNs expressing dopamine receptor type 1 (D1-MSNs). In contrast, cocaine promoted a rightward shift in the distribution of synaptic weights toward larger synaptic responses in MSNs expressing dopamine receptor type 2 (D2-MSNs). After chronic social defeat stress, resilient animals displayed an upregulation of synaptic strength at large mushroom spines of D1-MSNs and a concomitant downregulation in D2-MSNs. Although susceptible mice did not exhibit a significant overall change in synaptic strength on D1-MSNs or D2-MSNs, we observed a slight leftward shift in cumulative distribution of large synaptic responses in both cell types. This study provides the first functional cell type-specific and spine type-specific comparison of synaptic strength at a single spine level between cocaine-induced and stress-induced neuroadaptations and demonstrates that psychoactive drugs and stress trigger divergent changes in synaptic function in NAc. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
    Biological Psychiatry 06/2015; DOI:10.1016/j.biopsych.2015.05.022 · 10.26 Impact Factor
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    ABSTRACT: Exposures to various types of early life stress can be robust predictors of the development of psychiatric disorders, including depression and anxiety. The objective of the current study was to investigate the roles of the translationally relevant targets of central vasopressin, oxytocin, ghrelin, orexin, glucocorticoid, and the brain-derived neurotrophic factor (BDNF) pathway in an early chronic social stress (ECSS) based rodent model of postpartum depression and anxiety. The present study reports novel changes in gene expression and extracellular signal related kinase (ERK) protein levels in the brains of ECSS exposed rat dams that display previously reported depressed maternal care and increased maternal anxiety. Decreases in oxytocin, orexin, and ERK proteins, increases in ghrelin receptor, glucocorticoid and mineralocorticoid receptor mRNA levels, and bidirectional changes in vasopressin underscore related work on the adverse long-term effects of early life stress on neural activity and plasticity, maternal behavior, responses to stress, and depression and anxiety-related behavior. The differences in gene and protein expression and robust correlations between expression and maternal care and anxiety support increased focus on these targets in animal and clinical studies of the adverse effects of early life stress, especially those focusing on depression and anxiety in mothers and the transgenerational effects of these disorders on offspring. Copyright © 2015 Elsevier B.V. All rights reserved.
    Neuropeptides 05/2015; 52. DOI:10.1016/j.npep.2015.05.002 · 2.64 Impact Factor
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    ABSTRACT: Cue-induced methamphetamine seeking progressively increases after withdrawal (incubation of methamphetamine craving), but the underlying mechanisms are largely unknown. We determined whether this incubation is associated with alterations in candidate genes in dorsal striatum (DS), a brain area implicated in cue- and context-induced drug relapse. We first measured mRNA expression of 24 candidate genes in whole DS extracts after short (2 d) or prolonged (1 month) withdrawal in rats following extended-access methamphetamine or saline (control condition) self-administration (9 h/d, 10 d). We found minimal changes. Next, using fluorescence-activated cell sorting, we compared gene expression in Fos-positive dorsal striatal neurons, which were activated during “incubated” cue-induced drug-seeking tests after prolonged withdrawal, with nonactivated Fos-negative neurons. We found significant increases in mRNA expression of immediate early genes (Arc, Egr1), Bdnf and its receptor (Trkb), glutamate receptor subunits (Gria1, Gria3, Grm1), and epigenetic enzymes (Hdac3, Hdac4, Hdac5, GLP, Dnmt3a, Kdm1a) in the Fos-positive neurons only. Using RNAscope to determine striatal subregion and cell-type specificity of the activated neurons, we measured colabeling of Fos with Drd1 and Drd2 in three DS subregions. Fos expression was neither subregion nor cell-type specific (52.5 and 39.2% of Fos expression colabeled with Drd1 and Drd2, respectively). Finally, we found that DS injections of SCH23390 (C17H18ClNO), a D1-family receptor antagonist known to block cue-induced Fos induction, decreased incubated cue-induced methamphetamine seeking after prolonged withdrawal. Results demonstrate a critical role of DS in incubation of methamphetamine craving and that this incubation is associated with selective gene-expression alterations in cue-activated D1- and D2-expressing DS neurons.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 05/2015; 35(21):8232-8244. DOI:10.1523/JNEUROSCI.1022-15.2015 · 6.34 Impact Factor
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    ABSTRACT: ΔFosB is a stable transcription factor which accumulates in the nucleus accumbens (NAc), a key part of the brain’s reward circuitry, in response to chronic exposure to cocaine or other drugs of abuse. While ΔFosB is known to heterodimerize with a Jun family member to form an active transcription factor complex, there has not to date been an open-ended exploration of other possible binding partners for ΔFosB in the brain. Here, by use of yeast two-hybrid assays, we identify PSMC5—also known as SUG1, an ATPase-containing subunit of the 19S proteasomal complex—as a novel interacting protein with ΔFosB. We verify such interactions between endogenous ΔFosB and PSMC5 in the NAc and demonstrate that both proteins also form complexes with other chromatin regulatory proteins associated with gene activation. We go on to show that chronic cocaine increases nuclear, but not cytoplasmic, levels of PSMC5 in the NAc and that overexpression of PSMC5 in this brain region promotes the locomotor responses to cocaine. Together, these findings describe a novel mechanism that contributes to the actions of ΔFosB and, for the first time, implicates PSMC5 in cocaine-induced molecular and behavioral plasticity.
    PLoS ONE 05/2015; 10(5):e0126710. DOI:10.1371/journal.pone.0126710 · 3.23 Impact Factor
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    ABSTRACT: Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vHIP) and basolateral amygdala (AMY). Here, we demonstrate that glutamatergic vHIP afferents to NAc regulate susceptibility to chronic social defeat stress (CSDS). We observe reduced activity in vHIP in mice resilient to CSDS. Furthermore, attenuation of vHIP-NAc transmission by optogenetic induction of long-term depression is pro-resilient, whereas acute enhancement of this input is pro-susceptible. This effect is specific to vHIP afferents to the NAc, as optogenetic stimulation of either mPFC or AMY afferents to the NAc is pro-resilient. These data indicate that vHIP afferents to NAc uniquely regulate susceptibility to CSDS, highlighting an important, novel circuit-specific mechanism in depression.
    Nature Communications 05/2015; · 11.47 Impact Factor
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    ABSTRACT: Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vHIP) and basolateral amygdala (AMY). Here, we demonstrate that glutamatergic vHIP afferents to NAc regulate susceptibility to chronic social defeat stress (CSDS). We observe reduced activity in vHIP in mice resilient to CSDS. Furthermore, attenuation of vHIP-NAc transmission by optogenetic induction of long-term depression is pro-resilient, whereas acute enhancement of this input is pro-susceptible. This effect is specific to vHIP afferents to the NAc, as optogenetic stimulation of either mPFC or AMY afferents to the NAc is pro-resilient. These data indicate that vHIP afferents to NAc uniquely regulate susceptibility to CSDS, highlighting an important, novel circuit-specific mechanism in depression.
    Nature Communications 05/2015; 6:7062. DOI:10.1038/ncomms8062 · 11.47 Impact Factor
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    ABSTRACT: Chronic cocaine exposure increases the density of dendritic spines on medium spiny neurons (MSNs), the predominant neuronal cell type of the nucleus accumbens (NAc), a key brain reward region. We recently showed that suppression of Rac1, a small GTPase, is a critical mediator of this structural plasticity, but the upstream determinants of Rac1 activity in this context remain to be elucidated. In this study we examined whether isoforms of Dishevelled, a key hub protein of multiple branches of Wnt signaling, including Rac1, are regulated in the NAc by chronic cocaine, and whether these Dishevelled isoforms control Rac1 activity in this brain region in vivo. We found that chronic cocaine administration decreased expression of Dishevelled-2, and several other Wnt signaling components, in the NAc, and that overexpression of Dishevelled-2, but not Dishevelled-1, conversely upregulated Rac1 activity and prevented the cocaine induction of dendritic spines on NAc MSNs. We posit that the cocaine-induced downregulation of Dishevelled-2 in the NAc is an upstream regulator of Rac1 activity and plays an important role in the dynamic structural plasticity of NAc MSNs seen in response to chronic cocaine exposure. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Neuroscience Letters 05/2015; 598. DOI:10.1016/j.neulet.2015.05.003 · 2.03 Impact Factor
  • Herbert E Covington Iii · Ian Maze · Vincent Vialou · Eric J Nestler ·
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    ABSTRACT: Previous research has demonstrated antidepressant-like effects in rodents upon intracerebral inhibition of histone deacetylases (HDACs). Such effects have been reported for local HDAC inhibition in the nucleus accumbens, hippocampus, and amygdala. However, the effect of HDAC inhibition within the medial prefrontal cortex, which is integral to depression-related symptoms and their treatment, remains unknown. Here we show that local infusion of the highly selective HDAC inhibitor, MS-275, into medial prefrontal cortex exerts robust antidepressant-like effects in the chronic social defeat stress paradigm in mice. These findings provide further impetus for the assessment of HDAC inhibitors for the treatment of depression. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 04/2015; 298. DOI:10.1016/j.neuroscience.2015.04.030 · 3.36 Impact Factor
  • Eric J. Nestler ·
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    ABSTRACT: ΔFosB is a member of the Fos family of transcription factors. While other family members are induced rapidly but transiently in response to a host of acute stimuli, ΔFosB is unique in that it accumulates in response to repeated stimulation due to its unusual protein stability. Such prolonged induction of ΔFosB, within nucleus accumbens (NAc), a key brain reward region, has been most studied in animal models of drug addiction, with considerable evidence indicating that ΔFosB promotes reward and motivation and serves as a mechanism of drug sensitization and increased drug self-administration. In more recent years, prolonged induction of ∆FosB has also been observed within NAc in response to chronic administration of certain forms of stress. Increasing evidence indicates that this induction represents a positive, homeostatic adaptation to chronic stress, since overexpression of ∆FosB in this brain region promotes resilience to stress, whereas blockade of its activity promotes stress susceptibility. Chronic administration of several antidepressant medications also induces ∆FosB in the NAc, and this induction is required for the therapeutic-like actions of these drugs in mouse models. Validation of these rodent findings is the demonstration that depressed humans, examined at autopsy, display reduced levels of ∆FosB within the NAc. As a transcription factor, ΔFosB produces this behavioral phenotype by regulating the expression of specific target genes, which are under current investigation. These studies of ΔFosB are providing new insight into the molecular basis of depression and antidepressant action, which is defining a host of new targets for possible therapeutic development.
    European journal of pharmacology 04/2015; 753:66-72. DOI:10.1016/j.ejphar.2014.10.034 · 2.53 Impact Factor
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    ABSTRACT: Ten-eleven translocation (TET) enzymes mediate the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which is enriched in brain, and its ultimate DNA demethylation. However, the influence of TET and 5hmC on gene transcription in brain remains elusive. We found that ten-eleven translocation protein 1 (TET1) was downregulated in mouse nucleus accumbens (NAc), a key brain reward structure, by repeated cocaine administration, which enhanced behavioral responses to cocaine. We then identified 5hmC induction in putative enhancers and coding regions of genes that have pivotal roles in drug addiction. Such induction of 5hmC, which occurred similarly following TET1 knockdown alone, correlated with increased expression of these genes as well as with their alternative splicing in response to cocaine administration. In addition, 5hmC alterations at certain loci persisted for at least 1 month after cocaine exposure. Together, these reveal a previously unknown epigenetic mechanism of cocaine action and provide new insight into how 5hmC regulates transcription in brain in vivo.
    Nature Neuroscience 03/2015; 18(4). DOI:10.1038/nn.3976 · 16.10 Impact Factor
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    ABSTRACT: Neuropathic and inflammatory pain promote a large number of persisting adaptations at the cellular and molecular level, allowing even transient tissue or nerve damage to elicit changes in cells that contribute to the development of chronic pain and associated symptoms. There is evidence that injury-induced changes in chromatin structure drive stable changes in gene expression and neural function, which may cause several symptoms, including allodynia, hyperalgesia, anxiety, and depression. Recent findings on epigenetic changes in the spinal cord and brain during chronic pain may guide fundamental advances in new treatments. Here, we provide a brief overview of epigenetic regulation in the nervous system and then discuss the still-limited literature that directly implicates epigenetic modifications in chronic pain syndromes. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Trends in Neurosciences 03/2015; 38(4). DOI:10.1016/j.tins.2015.02.001 · 13.56 Impact Factor

Publication Stats

58k Citations
4,862.01 Total Impact Points


  • 2008-2015
    • Icahn School of Medicine at Mount Sinai
      • • Department of Pharmacology and Systems Therapeutics
      • • Department of Psychiatry
      • • Department of Neuroscience
      Borough of Manhattan, New York, United States
  • 2013
    • University of Crete
      • Division of Basic Sciences
      Retimo, Crete, Greece
  • 2006-2013
    • Stanford University
      • Department of Psychiatry and Behavioral Sciences
      Palo Alto, CA, United States
  • 2012
    • James J. Peters VA Medical Center
      New York, New York, United States
    • Tata Institute of Fundamental Research
      • Department of Biological Sciences
      Mumbai, State of Maharashtra, India
  • 2011
    • Mount Sinai Medical Center
      New York City, New York, United States
    • Mount Sinai Hospital
      New York, New York, United States
  • 2000-2011
    • University of Texas Southwestern Medical Center
      • Department of Psychiatry
      Dallas, TX, United States
    • Karolinska Institutet
      • Institutionen för neurovetenskap
      Solna, Stockholm, Sweden
  • 2000-2008
    • University of Texas at Dallas
      • Molecular Biology
      Richardson, Texas, United States
  • 1998-2006
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2005
    • Harvard Medical School
      • Department of Psychiatry
      Boston, MA, United States
    • University of Cambridge
      Cambridge, England, United Kingdom
  • 1985-2003
    • Yale-New Haven Hospital
      • • Department of Laboratory Medicine
      • • Department of Pathology
      New Haven, Connecticut, United States
  • 1981-2003
    • Yale University
      • Department of Psychiatry
      New Haven, CT, United States
  • 2002
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 1997
    • The Scripps Research Institute
      • Committee on the Neurobiology of Addictive Disorders
      لا هویا, California, United States
  • 1996
    • Community Health Center, Connecticut
      मिडलटाउन, Connecticut, United States
  • 1990
    • New York Medical College
      • Department of Biochemistry and Molecular Biology
      New York, New York, United States