Long-term imipramine treatment increases N-methyl-d-aspartate receptor activity and expression via epigenetic mechanisms

Nghia, Nguyen An; Hirasawa, Takae; Kasai, Hirotake; Obata, Chie; Moriishi, Kohji; Mochizuki, Kazuki; Koizumi, Schuichi; Kubota, Takeo

doi:10.1016/j.ejphar.2015.02.010

Cited by 24 publications

(13 citation statements)

References 45 publications

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“…A more recent study using engineered transcription factors (zinc finger proteins - ZFP) to site selectively remodel chromatin found that ZFP-induced enrichment of H3K9me2 at fosb gene in the NAc reduced both fosb/delta fosb expression and also induced anxiety and depressive-like behaviours following subthreshold social defeat stress [104]. Classical antidepressant medications, such as selective serotonin reuptake inhibitor (SSRI), imipramine was shown to increase NMDA receptor 2B (NR2B) subunit expression via mechanisms involving increased histone acetylation on the NR2B promoters and decreased activity of HDAC [105]. As mentioned previously expression of neurotropic factor BDNF is implicated in animal models of depression [12, 20].…”

Section: Epigenetic Mechanismsmentioning

confidence: 99%

Neuronal correlates of depression

Chaudhury

Liu

Han

2015

Cell. Mol. Life Sci.

125

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Major depressive disorder (MDD) is a common psychiatric disorder effecting approximately 121 million people worldwide and recent reports from the World Health Organization (WHO) suggest that it will be the leading contributor to the global burden of diseases. At present the most commonly used treatment strategies are still based on the monoamine hypothesis that has been the predominant theory in the last 60 years. Clinical observations that only a subset of depressed patients exhibits full remission when treated with classical monoamine-based antidepressants together with the fact that patients exhibit multiple symptoms suggest that the pathophysiology leading to mood disorders may differ between patients. Accumulating evidence indicates that depression is a neural circuit disorder and that onset of depression may be located at different regions of the brain involving different transmitter systems and molecular mechanisms. This review synthesizes findings from rodent studies from which emerges a role for different, yet interconnected, molecular systems and associated neural circuits to the etiology of depression.

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Section: Epigenetic Mechanismsmentioning

confidence: 99%

Neuronal correlates of depression

Chaudhury

Liu

Han

2015

Cell. Mol. Life Sci.

125

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“…Existing evidence suggests that changes in the DNA methylation level of specific genes are associated with vulnerability to depression (Hunter et al, 2009; Murgatroyd et al, 2009; Wilkinson et al, 2009; Zhang et al, 2010; Bagot et al, 2012). Chronic social defeat stress (CSDS) upregulated histone H3 acetylation in the rat hippocampus (Hollis et al, 2010), while long-term treatment with imipramine increased NR2B expression in mouse cortical neurons, via epigenetic changes, including increased histone H3K9 and H3K27 acetylation in the NR2B promoter (Nghia et al, 2015). These findings indicate that epigenetic modifications play an important role in the pathophysiology and treatment of depression (Bagot et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Activation of ASCT2 in the Hippocampus Contributes to Depression-Like Behavior by Regulating D-Serine in Mice

Wang

Zhang

Chen

et al. 2017

Front. Mol. Neurosci.

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The roles of D-serine in depression are raised concerned recently as an intrinsic co-agonist for the NMDA receptor. However, the mechanisms underlying its regulation are not fully elucidated. ASCT2 is a Na+-dependent D-serine transporter. We found that decreased D-serine and increased hippocampal ASCT2 levels correlated with chronic social defeat stress (CSDS) in mice. Lentivirus-mediated shRNA-mediated knockdown of ASCT2 and the administration of exogenous D-serine in the hippocampus alleviated CSDS-induced social avoidance and immobility. In vivo and in vitro experiments revealed that upregulation of ASCT2 expression in CSDS was regulated through histone hyper-acetylation, not DNA methylation in its promoter region. Immunohistochemistry demonstrated the co-localization of ASCT2 and D-serine. Uptake of D-serine by ASCT2 was demonstrated by in vivo and in vitro experiments. Our results indicate that CSDS induces ASCT2 expression through epigenetic activation and decreases hippocampal D-serine levels, leading to social avoidance, and immobility. Thus, targeting D-serine transport represents an attractive new strategy for treating depression.

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“…Furthermore, the expression of GluN2B subunits of cortical NMDA receptors is under monoamine‐modulated epigenetic control (Nghia et al., ). Interference with this regulation might thus impact NMDA receptor signalling later, at the time of behavioural training.…”

Section: Discussionmentioning

confidence: 99%

β‐adrenergic modulation of discrimination learning and memory in the auditory cortex

Schicknick

Henschke

Budinger

et al. 2019

Eur J of Neuroscience

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Despite vast literature on catecholaminergic neuromodulation of auditory cortex functioning in general, knowledge about its role for long‐term memory formation is scarce. Our previous pharmacological studies on cortex‐dependent frequency‐modulated tone‐sweep discrimination learning of Mongolian gerbils showed that auditory‐cortical D1/5‐dopamine receptor activity facilitates memory consolidation and anterograde memory formation. Considering overlapping functions of D1/5‐dopamine receptors and β‐adrenoceptors, we hypothesised a role of β‐adrenergic signalling in the auditory cortex for sweep discrimination learning and memory. Supporting this hypothesis, the β1/2‐adrenoceptor antagonist propranolol bilaterally applied to the gerbil auditory cortex after task acquisition prevented the discrimination increment that was normally monitored 1 day later. The increment in the total number of hurdle crossings performed in response to the sweeps per se was normal. Propranolol infusion after the seventh training session suppressed the previously established sweep discrimination. The suppressive effect required antagonist injection in a narrow post‐session time window. When applied to the auditory cortex 1 day before initial conditioning, β1‐adrenoceptor‐antagonising and β1‐adrenoceptor‐stimulating agents retarded and facilitated, respectively, sweep discrimination learning, whereas β2‐selective drugs were ineffective. In contrast, single‐sweep detection learning was normal after propranolol infusion. By immunohistochemistry, β1‐ and β2‐adrenoceptors were identified on the neuropil and somata of pyramidal and non‐pyramidal neurons of the gerbil auditory cortex. The present findings suggest that β‐adrenergic signalling in the auditory cortex has task‐related importance for discrimination learning of complex sounds: as previously shown for D1/5‐dopamine receptor signalling, β‐adrenoceptor activity supports long‐term memory consolidation and reconsolidation; additionally, tonic input through β1‐adrenoceptors may control mechanisms permissive for memory acquisition.

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Long-term imipramine treatment increases N-methyl-d-aspartate receptor activity and expression via epigenetic mechanisms

Cited by 24 publications

References 45 publications

Neuronal correlates of depression

Neuronal correlates of depression

Epigenetic Activation of ASCT2 in the Hippocampus Contributes to Depression-Like Behavior by Regulating D-Serine in Mice

β‐adrenergic modulation of discrimination learning and memory in the auditory cortex

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