scholarly journals Cognitive deficits triggered by early life stress: The role of histone deacetylase 1

2016 ◽  
Vol 94 ◽  
pp. 1-9 ◽  
Author(s):  
Samantha M. Adler ◽  
Claudia Schmauss
Keyword(s):  
Histone Deacetylase ◽  
Cognitive Deficits ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Histone Deacetylase 1

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 Sexual dimorphic role of the glucocorticoid receptor in chronic muscle pain produced by early-life stress

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Paul G Green ◽  
Pedro Alvarez ◽  
Jon D Levine
Keyword(s):  
Glucocorticoid Receptor ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Glucocorticoid Receptors ◽  
Early Life Stress ◽  
Nociceptive Threshold ◽  
Male And Female ◽  
Mechanical Nociceptive Threshold

Fibromyalgia and other chronic musculoskeletal pain syndromes are associated with stressful early life events, which can produce a persistent dysregulation in the hypothalamic-pituitary adrenal (HPA) stress axis function, associated with elevated plasm levels of corticosterone in adults. To determine the contribution of the HPA axis to persistent muscle hyperalgesia in adult rats that had experienced neonatal limited bedding (NLB), a form of early-life stress, we evaluated the role of glucocorticoid receptors on muscle nociceptors in adult NLB rats. In adult male and female NLB rats, mechanical nociceptive threshold in skeletal muscle was significantly lower than in adult control (neonatal standard bedding) rats. Furthermore, adult males and females that received exogenous corticosterone (via dams’ milk) during postnatal days 2–9, displayed a similar lowered mechanical nociceptive threshold. To test the hypothesis that persistent glucocorticoid receptor signaling in the adult contributes to muscle hyperalgesia in NLB rats, nociceptor expression of glucocorticoid receptor (GR) was attenuated by spinal intrathecal administration of an oligodeoxynucleotide (ODN) antisense to GR mRNA. In adult NLB rats, GR antisense markedly attenuated muscle hyperalgesia in males, but not in females. These findings indicate that increased corticosterone levels during a critical developmental period (postnatal days 2–9) produced by NLB stress induces chronic mechanical hyperalgesia in male and female rats that persists in adulthood, and that this chronic muscle hyperalgesia is mediated, at least in part, by persistent stimulation of glucocorticoid receptors on sensory neurons, in the adult male, but not female rat.

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 Role of Early Life Stress in HPA Axis and Anxiety

2020 ◽  
pp. 141-153 ◽  
Author(s):  
Mario F. Juruena ◽  
Filip Eror ◽  
Anthony J. Cleare ◽  
Allan H. Young
Keyword(s):  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress

Neurodevelopmental plasticity and psychiatric vulnerability

2015 ◽  
Vol 30 (S2) ◽  
pp. S70-S70
Author(s):  
A. Dayer
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Methylation Status ◽  
Early Life Stress ◽  
Childhood Adversity ◽  
Cellular Level ◽  
Special Focus ◽  
Serotonin System ◽  
Increase Risk

The early developmental period is characterized by a high degree of plasticity and, consequently, is very sensitive to environmental factors, such as early life stressors (ELS). Exposure to ELS is known to increase risk to psychopathologies such as depression and anxiety disorders later in life . At a cellular level, alterations in the migration and integration of GABAergic interneurons (INs) in cortical circuits have emerged as a key processes involved in the vulnerability to psychiatric disorders . In humans and rodents, ELS interacts with genes regulating the serotonin system to increase risk to stress-related disorders . In addition, ELS is associated to a variety of epigenetic methylation changes in blood DNA from patients displaying a high loading of ELS . Here, we aimed to investigate the role of the ionotropic serotonin 3A receptor (5-HT3AR) at a genetic and epigenetic level in rodent and human models of early-life stress. We will first present data indicating that the 5-HT3AR is specifically expressed in a subset of cortical INs derived from the caudal ganglionic eminence (CGE) and controls early steps of cortical circuit assembly . Interestingly, the migration, transcriptional programs and positioning of 5-HT3AR expressing interneuron subtypes were found to be dysregulated in pathological models of early-life serotonin dysregulation. At a behavioral level, we found that ELS interacts with the 5-HTR3A to modulate social behaviors. Finally, we will present human data indicating that childhood adversity significantly impacts the methylation status of the promoter region of the human 5-HT3AR in an allele-specific manner. Taken together, this presentation will highlight the importance of the serotonin system in early life development and psychopathology with a special focus on the role of the 5-HT3AR in cortical interneuron development.

Cytokines during acute abstinence of crack cocaine: The role of early life stress

2015 ◽  
Vol 146 ◽  
pp. e127
Author(s):  
Rodrigo Grassi-Oliveira ◽  
Mateus L. Levandowski ◽  
Thiago W. Viola ◽  
Luiz E. Wearick ◽  
Julio Carlos Pezzi ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Crack Cocaine ◽  
Early Life Stress

scholarly journals Forebrain CRF1 Modulates Early-Life Stress-Programmed Cognitive Deficits

2011 ◽  
Vol 31 (38) ◽  
pp. 13625-13634 ◽  
Author(s):  
X.-D. Wang ◽  
G. Rammes ◽  
I. Kraev ◽  
M. Wolf ◽  
C. Liebl ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress

Riluzole Normalizes Early-Life Stress-Induced Visceral Hypersensitivity in Rats: Role of Spinal Glutamate Reuptake Mechanisms

2010 ◽  
Vol 138 (7) ◽  
pp. 2418-2425 ◽  
Author(s):  
Romain–Daniel Gosselin ◽  
Richard M. O'Connor ◽  
Monica Tramullas ◽  
Marcela Julio–Pieper ◽  
Timothy G. Dinan ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Visceral Hypersensitivity

scholarly journals Hippocampal astroglial hypertrophy in mice subjected to early life maternal deprivation

2021 ◽  
Author(s):  
Arnab Nandi ◽  
Garima Virmani ◽  
Swananda Marathe
Keyword(s):  
Immune Responses ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Stratum Radiatum ◽  
Late Adulthood ◽  
Synaptic Physiology ◽  
And Behavior

Early-life stress (ELS), including chronic deprivation of maternal care, exerts persistent life-long effects on animal physiology and behavior, and is associated with several neurodevelopmental disorders. Long-lasting changes in neuronal plasticity and electrophysiology are documented extensively in the animal models of ELS. However, the role of astroglia in the lasting effects of ELS remains elusive. Astrocytes are intricately involved in the regulation of synaptic physiology and behavior. Moreover, astrocytes play a major role in the innate and adaptive immune responses in the central nervous system (CNS). The role of immune responses and neuroinflammation in the altered brain development and persistent adverse effects of ELS are beginning to be explored. Innate immune response in the CNS is characterized by a phenomenon called astrogliosis, a process in which astrocytes undergo hypertrophy, along with changes in gene expression and function. While the immune activation and neuroinflammatory changes concomitant with ELS, or in juveniles and young adults have been reported, it is unclear whether mice subjected to ELS exhibit astrogliosis-like alterations well into late-adulthood. Here, we subjected mice to maternal separation from postnatal day 2 to day 22 and performed comprehensive morphometric analysis of hippocampal astrocytes during late-adulthood. We found that the astrocytes in the stratum radiatum region of the CA1 hippocampal subfield from maternally separated mice exhibit significant hypertrophy as late as 8 months of age, revealing the crucial changes in astrocytes that manifest long after the cessation of ELS. This study highlights the persistence of neuroinflammatory changes in mice exposed to ELS.

Sign in / Sign up

Export Citation Format

Share Document