Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action

  title={Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action},
  author={Nadia M. Tsankova and Olivier Berton and William Renthal and Arvind Kumar and Rachel L Neve and Eric J. Nestler},
  journal={Nature Neuroscience},
To better understand the molecular mechanisms of depression and antidepressant action, we administered chronic social defeat stress followed by chronic imipramine (a tricyclic antidepressant) to mice and studied adaptations at the levels of gene expression and chromatin remodeling of five brain-derived neurotrophic factor (Bdnf) splice variant mRNAs (I–V) and their unique promoters in the hippocampus. Defeat stress induced lasting downregulation of Bdnf transcripts III and IV and robustly… 

Antidepressant Actions of Histone Deacetylase Inhibitors

It is found that chronic social defeat stress in mice causes a transient decrease, followed by a persistent increase, in levels of acetylated histone H3 in the nucleus accumbens, an important limbic brain region.

Imipramine Treatment and Resiliency Exhibit Similar Chromatin Regulation in the Mouse Nucleus Accumbens in Depression Models

The results demonstrate that chronic defeat stress causes widespread and long-lasting changes in gene regulation, including alterations in repressive histone methylation and in phospho-CREB (cAMP response element-binding protein) binding, in the mouse nucleus accumbens (NAc), a key brain reward region implicated in depression.

An HDAC-dependent epigenetic mechanism that enhances the efficacy of the antidepressant drug fluoxetine

It is shown that reducing HDAC activity in fluoxetine-treated Balb/c mice leads to robust antidepressant and anxiolytic effects, and that the HDAC-triggered epigenetic stimulation of Bdnf expression is critical for therapeutic efficacy.

Hippocampal HDAC4 Contributes to Postnatal Fluoxetine-Evoked Depression-Like Behavior

It is shown that viral-mediated hippocampal overexpression of Hdac4 was sufficient to induce depression-, but not anxiety-, like behavior in adulthood, and implicate HDAC4 in the dysregulated gene expression and emergence of perturbed emotionality following fluoxetine exposure in early life.

Modulation of DNA Methylation and Gene Expression in Rodent Cortical Neuroplasticity Pathways Exerts Rapid Antidepressant-Like Effects

It is suggested that acute inhibition of stress-induced DNA methylation promotes rapid and sustained antidepressant effects associated with increased BDNF-TrkB-mTOR signaling in the PFC.

Antidepressant-like effect of sodium butyrate (HDAC inhibitor) and its molecular mechanism of action in the rat hippocampus

Findings suggest the possibility that alterations in gene expression, including upregulation of Ttr and downregulation of several other genes, including Htr2a, may be involved in antidepressant-like effect of SB.

Aberrant HDAC2-Mediated Histone Modifications and Synaptic Plasticity in the Amygdala Predisposes to Anxiety and Alcoholism

The data suggest that HDAC2-induced chromatin remodeling in the CeA and MeA, but not BLA may be involved in controlling baseline anxiety or anxiolytic effects of ethanol in P rats compared to NP rats, and results confirm thatHDAC2 siRNA infusion causes a significant reduction in HDACs mRNA levels inThe CeA.



Histone Modifications at Gene Promoter Regions in Rat Hippocampus after Acute and Chronic Electroconvulsive Seizures

The findings suggest that the chronic downregulation of c-fos transcription, observed in this study, may be achieved at the level of H4 acetylation, whereas chronic upregulation of BDNF transcription may be sustained via control of H3 acetylations, selectively at the BDNF P3 and P4 promoters.

Altered Histone Acetylation at Glutamate Receptor 2 and Brain-Derived Neurotrophic Factor Genes Is an Early Event Triggered by Status Epilepticus

It is found that acetylation of histone H4 in rat hippocampal CA3 neurons was reduced at the glutamate receptor 2 (GluR2; GRIA2) glutamate receptor promoter but increased at brain-derived neurotrophic factor promoter P2 as soon as 3 hr after induction of status epilepticus by pilocarpine, indicating that status epileptus rapidly activates different signal pathways to modulate histone acetylations in a promoter-specific manner.

Regulation of Histone Acetylation during Memory Formation in the Hippocampus*

Results indicate that histone-associated heterochromatin undergoes changes in structure during the formation of long term memory, which enhances a cellular process thought to underlie longterm memory formation, hippocampal long term potentiation, and memory formation itself.

Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus

It is demonstrated that BDNF and NT-3 are stress-responsive genes and the possibility that alterations in the expression of these or other growth factors might be important in producing some of the physiological and pathophysiological effects of stress in the hippocampus is raised.

Brain-Derived Neurotrophic Factor Produces Antidepressant Effects in Behavioral Models of Depression

The hypothesis that BDNF in the hippocampus produces an antidepressant effect in behavioral models of depression, the learned helplessness (LH) and forced swim test (FST) paradigms is tested and provides further support for the hypothesis thatBDNF contributes to the therapeutic action of antidepressant treatment.

Structural plasticity and tianeptine: cellular and molecular targets

Histone deacetylase activity is retained in primary neurons expressing mutant huntingtin protein

Perturbation of histone acetyl‐transferase (HAT) activity is implicated in the pathology of polyglutamine diseases, and suppression of the counteracting histone deacetylase (HDAC) proteins has been

Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice