H3K9me2 regulation of BDNF expression in the hippocampus and medial prefrontal cortex is involved in the depressive-like phenotype induced by maternal separation in male rats

Jiang, Zhijun; Zhu, Zemeng; Zhao, Mingyue; Wang, Wei; Li, Haonan; Liu, Dexiang; Pan, Fang

doi:10.1007/s00213-021-05896-7

Cited by 21 publications

(9 citation statements)

References 52 publications

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“…More importantly, SIK1 knockdown remarkably enhanced the expression of CRH in the PVN (Figure 2C), consistent with the corticosterone and ACTH results in Figure 2B. Depression is accompanied by some critical pathological phenomena that can be attributed to the excessive release of glucocorticoids, such as decreased hippocampal neurogenesis and a downregulated brain-derived neurotrophic factor (BDNF) signalling cascade in the hippocampus and mPFC (Jiang et al, 2021;Liu et al, 2020;Masi and Brovedani, 2011;Mahar et al, 2014;Snyder et al, 2011). Interestingly, Figure 2D shows that the mice infused with SIK1-shRNA had signi cantly lower protein levels of BDNF, phosphorylated tyrosine receptor kinase B (pTrkB), and phosphorylated CREB (pCREB) in the hippocampus and mPFC than those of control mice, whereas the expression of total β-actin, TrkB, and CREB among all groups remained unchanged.…”

Section: Resultssupporting

confidence: 82%

Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic–pituitary–adrenal axis

Wang

Liu

et al. 2022

Mol Psychiatry

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Elucidating the molecular mechanism underlying the hyperactivity of the hypothalamic-pituitaryadrenal axis during chronic stress is critical for understanding depression and treating depression. The secretion of corticotropin-releasing hormone (CRH) from neurons in the paraventricular nucleus (PVN) of the hypothalamus is controlled by salt-inducible kinases (SIKs) and CREB-regulated transcription coactivators (CRTCs). We hypothesized that the SIK-CRTC system in the PVN might contribute to the pathogenesis of depression. Thus, the present study employed chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, virus-mediated gene transfer, enzyme linked immunosorbent assay, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription polymerase chain reaction, and immuno uorescence to investigate this connection. Our results revealed that both CSDS and CUMS induced signi cant changes in SIK1-CRTC1 signaling in PVN neurons. Both genetic knockdown of SIK1 and genetic overexpression of CRTC1 in the PVN simulated chronic stress, producing a depression-like phenotype in naïve mice, and the CRTC1-CREB-CRH pathway mediates the pro-depressant actions induced by SIK1 knockdown in the PVN.In contrast, both genetic overexpression of SIK1 and genetic knockdown of CRTC1 in the PVN protected against CSDS and CUMS, leading to antidepressant-like effects in mice. Moreover, stereotactic infusion of TAT-SIK1 into the PVN also produced bene cial effects against chronic stress. Furthermore, the SIK1-CRTC1 system in the PVN played a role in the antidepressant actions of uoxetine, paroxetine, venlafaxine, and duloxetine. Collectively, SIK1 and CRTC1 in PVN neurons are closely involved in depression neurobiology, and they could be viable targets for novel antidepressants.

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Section: Resultssupporting

confidence: 82%

Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic–pituitary–adrenal axis

Wang

Liu

et al. 2022

Mol Psychiatry

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“…The medial prefrontal cortex (mPFC), a crucial region that is implicated in the pathophysiology of emotional disorders ( Liu et al, 2012 ; Zhang et al, 2017 ; Liang et al, 2018 ), is sensitive to stress exposure in early life ( McKlveen et al, 2013 , 2015 ). Several studies have shown that maternal separation (MS) induces an increase in 5-hydroxytryptamine transporter expression and decrease in brain-derived neurotrophic factor (BDNF) levels in rat mPFC ( Park et al, 2012 ; Jiang et al, 2021 ; Tata et al, 2021 ). MS results in decreased neuron excitability and abnormal myelin formation in the mPFC ( Liu et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Early Life Stress Induces Different Behaviors in Adolescence and Adulthood May Related With Abnormal Medial Prefrontal Cortex Excitation/Inhibition Balance

et al. 2022

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Early life stress is thought to be a risk factor for emotional disorders, particularly depression and anxiety. Although the excitation/inhibition (E/I) imbalance has been implicated in neuropsychiatric disorders, whether early life stress affects the E/I balance in the medial prefrontal cortex at various developmental stages is unclear. In this study, rats exposed to maternal separation (MS) that exhibited a well-established early life stress paradigm were used to evaluate the E/I balance in adolescence (postnatal day P43–60) and adulthood (P82–100) by behavior tests, whole-cell recordings, and microdialysis coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. First, the behavioral tests revealed that MS induced both anxiety- and depressive-like behaviors in adolescent rats but only depressive-like behavior in adult rats. Second, MS increased the action potential frequency and E/I balance of synaptic transmission onto L5 pyramidal neurons in the prelimbic (PrL) brain region of adolescent rats while decreasing the action potential frequency and E/I balance in adult rats. Finally, MS increases extracellular glutamate levels and decreased the paired-pulse ratio of evoked excitatory postsynaptic currents (EPSCs) of pyramidal neurons in the PrL of adolescent rats. In contrast, MS decreased extracellular glutamate levels and increased the paired-pulse ratio of evoked EPSCs of pyramidal neurons in the PrL of adult rats. The present results reveal a key role of E/I balance in different MS-induced disorders may related to the altered probability of presynaptic glutamate release at different developmental stages.

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“…G9a inhibitor relieved depression behavior with decreasing H3K9me2. 269 , 270 Conversely, chronic social stress decreased G9a expression and H3K9me2 in NAc. 271 These studies suggested that the differential levels of G9a-mediated H3K9me2 according to brain regions are associated with MDD.…”

Section: Histone Modification In Neuropsychiatric Disordersmentioning

confidence: 99%

The role of histone modifications: from neurodevelopment to neurodiseases

Park

Lee

Kim

et al. 2022

Sig Transduct Target Ther

126

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Epigenetic regulatory mechanisms, including DNA methylation, histone modification, chromatin remodeling, and microRNA expression, play critical roles in cell differentiation and organ development through spatial and temporal gene regulation. Neurogenesis is a sophisticated and complex process by which neural stem cells differentiate into specialized brain cell types at specific times and regions of the brain. A growing body of evidence suggests that epigenetic mechanisms, such as histone modifications, allow the fine-tuning and coordination of spatiotemporal gene expressions during neurogenesis. Aberrant histone modifications contribute to the development of neurodegenerative and neuropsychiatric diseases. Herein, recent progress in understanding histone modifications in regulating embryonic and adult neurogenesis is comprehensively reviewed. The histone modifications implicated in neurodegenerative and neuropsychiatric diseases are also covered, and future directions in this area are provided.

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H3K9me2 regulation of BDNF expression in the hippocampus and medial prefrontal cortex is involved in the depressive-like phenotype induced by maternal separation in male rats

Cited by 21 publications

References 52 publications

Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic–pituitary–adrenal axis

Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic–pituitary–adrenal axis

Early Life Stress Induces Different Behaviors in Adolescence and Adulthood May Related With Abnormal Medial Prefrontal Cortex Excitation/Inhibition Balance

The role of histone modifications: from neurodevelopment to neurodiseases

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