scholarly journals HDAC1 links early life stress to schizophrenia-like phenotypes

2017 ◽  
Vol 114 (23) ◽  
pp. E4686-E4694 ◽  
Author(s):  
Sanaz Bahari-Javan ◽  
Hristo Varbanov ◽  
Rashi Halder ◽  
Eva Benito ◽  
Lalit Kaurani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Dna Methylation ◽  
Prefrontal Cortex ◽  
Histone Deacetylase ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Blood Samples ◽  
Histone Deacetylase 1 ◽  
Disease Phenotypes

Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS. Systemic administration of an HDAC inhibitor rescues the detrimental effects of ELS when applied after the manifestation of disease phenotypes. In addition to the hippocampus and prefrontal cortex, mice subjected to ELS exhibit increased Hdac1 expression in blood. Moreover, Hdac1 levels are increased in blood samples from patients with schizophrenia who had encountered ELS, compared with patients without ELS experience. Our data suggest that HDAC1 inhibition should be considered as a therapeutic approach to treat schizophrenia.

scholarly journals Maternal Depression, Child Temperament, and Early-Life Stress Predict Never-Depressed Preadolescents’ Functional Connectivity During a Negative-Mood Induction

2021 ◽  
pp. 216770262110164
Author(s):  
Pan Liu ◽  
Matthew R. J. Vandermeer ◽  
Ola Mohamed Ali ◽  
Andrew R. Daoust ◽  
Marc F. Joanisse ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Maternal Depression ◽  
Life Stress ◽  
Early Life ◽  
Negative Emotion ◽  
Negative Mood ◽  
Emotion Processing ◽  
Early Life Stress ◽  
Cingulate Cortex

Understanding the development of depression can inform etiology and prevention/intervention. Maternal depression and maladaptive patterns of temperament (e.g., low positive emotionality [PE] or high negative emotionality, especially sadness) are known to predict depression. Although it is unclear how these risks cause depression, altered functional connectivity (FC) during negative-emotion processing may play an important role. We investigated whether maternal depression and age-3 emotionality predicted FC during negative mood reactivity in never-depressed preadolescents and whether these relationships were augmented by early-life stress. Maternal depression predicted decreased medial prefrontal cortex (mPFC)–amygdala and mPFC–insula FC but increased mPFC–posterior cingulate cortex (PCC) FC. PE predicted increased dorsolateral prefrontal cortex–amygdala FC, whereas sadness predicted increased PCC-based FC in insula, orbitofrontal cortex, and anterior cingulate cortex (ACC). Sadness was more strongly associated with PCC–insula and PCC–ACC FC as early stress increased. Findings indicate that early depression risks may be mediated by FC underlying negative-emotion processing.

Impact of early-life stress on the medial prefrontal cortex functions – a search for the pathomechanisms of anxiety and mood disorders

2013 ◽  
Vol 65 (6) ◽  
pp. 1462-1470 ◽  
Author(s):  
Agnieszka Chocyk ◽  
Iwona Majcher-Maślanka ◽  
Dorota Dudys ◽  
Aleksandra Przyborowska ◽  
Krzysztof Wędzony
Keyword(s):  
Prefrontal Cortex ◽  
Mood Disorders ◽  
Medial Prefrontal Cortex ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress

Abstract 335: Vascular Histone Deacetylase Mediates Early Life Stress-Induced Endothelial Dysfunction

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Dao H Ho ◽  
Jennifer S Pollock
Keyword(s):  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Histone Deacetylase ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Chromatin Modification ◽  
Early Life Stress ◽  
Mrna Levels

Chromatin remodeling is an important factor in the etiology of vascular pathologies. Also, early life stress (ELS) is linked to increased risk of vascular disease in adults. We used maternal separation with early weaning (MSEW) to study mechanisms of ELS-mediated adult vascular dysfunction in male C57BL/6J mice. Litters were subjected to maternal separation 4h/day (postnatal day (PD) 2-5) and 8h/day (PD6-16), and weaned at PD17. Control (CON) litters were undisturbed until weaning at PD21. Subsequent experiments were performed at 12 weeks old. MSEW blunted aortic ACh-mediated vasorelaxation (MSEW: 68% vs CON: 90%, p=0.01), while SNP-induced vasorelaxation was similar in CON and MSEW aortae. Apocynin (300 μM) and superoxide dismutase (100 U/mL) normalized MSEW-induced endothelial dysfunction. We hypothesize that ELS induces aortic endothelial dysfunction by increasing NADPH oxidase expression and/or decreasing nitric oxide synthase 3 (NOS3) expression. Aortic protein expression of NADPH oxidase subunit p67 was elevated in MSEW mice (45% increase from CON, n=11, p=0.02). NOS3 protein expression and NOS3 serine 1177 phosphorylation was not different between groups, indicating that NOS3 activation by phosphorylation does not contribute to ELS-induced endothelial dysfunction. We further hypothesize that chromatin modification mediates ELS-induced endothelial dysfunction. Aortic mRNA expressions of 84 chromatin modification enzymes (methyltransferases, demethylases, acetyltransferases, deacetylases) were assessed by qRT-PCR. Only histone deacetylase (HDAC) 1, 6 and 9 mRNA levels were significantly upregulated in MSEW aortae compared to CON (17%, 29% and 67% increase, respectively, p<0.05). However, only HDAC 9 protein expression was elevated in MSEW aortae (2 fold increase from CON, n=6, p=0.01). Accordingly, histone 3 lysine acetylation was slightly decreased in MSEW aortae (16% decrease from CON, n=6, p = 0.06). Pretreatment of aortae with an HDAC inhibitor, trichostatin A (TSA), normalized ACh-induced vasorelaxation in MSEW mice (MSEW: 68% vs MSEW + TSA: 88%, p=0.02), while not affecting ACh-induced vasorelaxation in CON mice. We conclude that ELS induces endothelial dysfunction, most likely, through an HDAC 9-mediated pathway.

The effects of early life stress on the excitatory/inhibitory balance of the medial prefrontal cortex

2020 ◽  
Vol 379 ◽  
pp. 112306 ◽  
Author(s):  
Ken-ichi Ohta ◽  
Shingo Suzuki ◽  
Katsuhiko Warita ◽  
Kazunori Sumitani ◽  
Chiaki Tenkumo ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress
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