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https://www.readbyqxmd.com/read/28434943/epigenetic-pathways-in-human-disease-the-impact-of-dna-methylation-on-stress-related-pathogenesis-and-current-challenges-in-biomarker-development
#1
M Austin Argentieri, Sairaman Nagarajan, Bobak Seddighzadeh, Andrea A Baccarelli, Alexandra E Shields
HPA axis genes implicated in glucocorticoid regulation play an important role in regulating the physiological impact of social and environmental stress, and have become a focal point for investigating the role of glucocorticoid regulation in the etiology of disease. We conducted a systematic review to critically assess the full range of clinical associations that have been reported in relation to DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5, and HSD11β1/2 genes in adults...
April 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28434031/fkbp51s-signature-in-peripheral-blood-mononuclear-cells-of-melanoma-patients-as-a-possible-predictive-factor-for-immunotherapy
#2
Simona Romano, Ester Simeone, Anna D'Angelillo, Paolo D'Arrigo, Michele Russo, Mario Capasso, Vito Alessandro Lasorsa, Nicola Zambrano, Paolo A Ascierto, Maria Fiammetta Romano
The inhibitory immune checkpoint PD-L1/PD1 promotes the alternative splicing of the FKBP5 gene, resulting in increased expression of its variant 4 in the peripheral blood mononuclear cells of melanoma patients. The variant 4 transcript is translated into the truncated FKBP51s protein. Given the importance of co-inhibitory signalling in tumour immune escape, here we tested the potential for using FKBP51s expression to predict immunotherapy outcomes. To do this, we immunophenotyped PBMCs from 118 melanoma patients and 77 age- and sex-matched healthy controls...
April 22, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28428441/selective-glucocorticoid-receptor-modulators-sgrms-delay-castrate-resistant-prostate-cancer-growth
#3
Jacob Kach, Tiha M Long, Phillip Selman, Eva Y Tonsing-Carter, Maria A Bacalao, Ricardo R Lastra, Larischa de Wet, Shane Comiskey, Marc Gillard, Calvin VanOpstall, Diana C West, Wen-Ching Chan, Donald Vander Griend, Suzanne D Conzen, Russell Z Szmulewitz
Increased glucocorticoid receptor (GR) expression and activity following androgen blockade can contribute to castration-resistant prostate cancer (CRPC) progression. Therefore, we hypothesized that GR antagonism will have therapeutic benefit in CRPC. However, the FDA-approved nonselective, steroidal GR antagonist, mifepristone, lacks GR specificity, reducing its therapeutic potential. Here we report that two novel non-steroidal and highly selective GR modulators (SGRMs), CORT118335 and CORT108297, have the ability to block GR activity in prostate cancer (PC) and slow CRPC progression...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28401840/methylation-matters-fk506-binding-protein-51-fkbp5-methylation-moderates-the-associations-of-fkbp5-genotype-and-resistant-attachment-with-stress-regulation
#4
Rosa H Mulder, Jolien Rijlaarsdam, Maartje P C M Luijk, Frank C Verhulst, Janine F Felix, Henning Tiemeier, Marian J Bakermans-Kranenburg, Marinus H Van Ijzendoorn
The parent-child attachment relationship plays an important role in the development of the infant's stress regulation system. However, genetic and epigenetic factors such as FK506 binding protein 51 (FKBP5) genotype and DNA methylation have also been associated with hypothalamus-pituitary-adrenal axis functioning. In the current study, we examined how parent-child dyadic regulation works in concert with genetic and epigenetic aspects of stress regulation. We study the associations of attachment, extreme maternal insensitivity, FKBP5 single nucleotide polymorphism 1360780, and FKBP5 methylation, with cortisol reactivity to the Strange Situation Procedure in 298 14-month-old infants...
May 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28393267/charting-the-perfect-storm-emerging-biological-interfaces-between-stress-and-stroke
#5
REVIEW
G Kronenberg, J Schöner, C Nolte, A Heinz, M Endres, Karen Gertz
A growing body of evidence demonstrates that psychosocial stress is an important and often underestimated risk factor for cardiovascular disease such as myocardial infarction and stroke. In this article, we map out major biological interfaces between stress, stress-related psychiatric disorders, and stroke, placing special emphasis on the fact that stress and psychiatric disorders may be both cause and consequence of cardiovascular disease. Apart from high-risk lifestyle habits such as smoking and lack of exercise, neuroendocrine dysregulation, alterations of the hemostatic system, increased oxidative stress, and inflammatory changes have been implicated in stress-related endothelial dysfunction...
April 9, 2017: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28386555/analysis-of-differentially-expressed-genes-in-gastrocnemius-muscle-between-dgat1-transgenic-mice-and-wild-type-mice
#6
Fei Ying, Hao Gu, Yuanzhu Xiong, Bo Zuo
Adipose tissue was the major energy deposition site of the mammals and provided the energy for the body and released the external pressure to the internal organs. In animal production, fat deposition in muscle can affect the meat quality, especially the intramuscular fat (IMF) content. Diacylglycerol acyltransferase-1 (DGAT1) was the key enzyme to control the synthesis of the triacylglycerol in adipose tissue. In order to better understand the regulation mechanism of the DGAT1 in the intramuscular fat deposition, the global gene expression profiling was performed in gastrocnemius muscle between DGAT1 transgenic mice and wild-type mice by microarray...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28374949/post-traumatic-stress-disorder-and-beyond-an-overview-of-rodent-stress-models
#7
REVIEW
Johanna Schöner, Andreas Heinz, Matthias Endres, Karen Gertz, Golo Kronenberg
Post-traumatic stress disorder (PTSD) is a psychiatric disorder of high prevalence and major socioeconomic impact. Patients suffering from PTSD typically present intrusion and avoidance symptoms and alterations in arousal, mood and cognition that last for more than 1 month. Animal models are an indispensable tool to investigate underlying pathophysiological pathways and, in particular, the complex interplay of neuroendocrine, genetic and environmental factors that may be responsible for PTSD induction. Since the 1960s, numerous stress paradigms in rodents have been developed, based largely on Seligman's seminal formulation of 'learned helplessness' in canines...
April 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28364727/hypothalamic-pituitary-adrenal-axis-genetic-variation-and-early-stress-moderates-amygdala-function
#8
Christina R Di Iorio, Caitlin E Carey, Lindsay J Michalski, Nadia S Corral-Frias, Emily Drabant Conley, Ahmad R Hariri, Ryan Bogdan
Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms...
March 12, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28338058/the-role-of-creb3l4-in-the-proliferation-of-prostate-cancer-cells
#9
Tae-Hyun Kim, Joo-Man Park, Mi-Young Kim, Yong-Ho Ahn
The incidence of prostate cancer (PC) is growing rapidly throughout the world, in probable association with the adoption of western style diets. Thus, understanding the molecular pathways triggering the development of PC is crucial for both its prevention and treatment. Here, we investigated the role of the metabolism-associated protein, CREB3L4, in the proliferation of PC cells. CREB3L4 was upregulated by the synthetic androgen, R1881, in LNCaP PC cells (an androgen-dependent cell line). Knockdown of CREB3L4 resulted in decreased androgen-dependent PC cell growth...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320277/mechanisms-of-brain-glucocorticoid-resistance-in-stress-induced-psychopathologies
#10
REVIEW
V M Merkulov, T I Merkulova, N P Bondar
Exposure to stress activates the hypothalamic-pituitary-adrenal axis and leads to increased levels of glucocorticoid (GC) hormones. Prolonged elevation of GC levels causes neuronal dysfunction, decreases the density of synapses, and impairs neuronal plasticity. Decreased sensitivity to glucocorticoids (glucocorticoid resistance) that develops as a result of chronic stress is one of the characteristic features of stress-induced psychopathologies. In this article, we reviewed the published data on proposed molecular mechanisms that contribute to the development of glucocorticoid resistance in brain, including changes in the expression of the glucocorticoid receptor (GR) gene, biosynthesis of GR isoforms, and GR posttranslational modifications...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28319850/methylation-of-hpa-axis-related-genes-in-men-with-hypersexual-disorder
#11
Jussi Jokinen, Adrian E Boström, Andreas Chatzittofis, Diana M Ciuculete, Katarina Görts Öberg, John N Flanagan, Stefan Arver, Helgi B Schiöth
Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality...
March 10, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28300138/reduced-dna-methylation-and-psychopathology-following-endogenous-hypercortisolism-a-genome-wide-study
#12
Camilla A M Glad, Johanna C Andersson-Assarsson, Peter Berglund, Ragnhildur Bergthorsdottir, Oskar Ragnarsson, Gudmundur Johannsson
Patients with Cushing's Syndrome (CS) in remission were used as a model to test the hypothesis that long-standing excessive cortisol exposure induces changes in DNA methylation that are associated with persisting neuropsychological consequences. Genome-wide DNA methylation was assessed in 48 women with CS in long-term remission (cases) and 16 controls matched for age, gender and education. The Fatigue impact scale and the comprehensive psychopathological rating scale were used to evaluate fatigue, depression and anxiety...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298552/dynamic-expression-of-fkbp5-in-the-medial-prefrontal-cortex-regulates-resiliency-to-conditioned-fear
#13
Marangelie Criado-Marrero, Roberto J Morales Silva, Bethzaly Velazquez, Anixa Hernández, María Colon, Emmanuel Cruz, Omar Soler-Cedeño, James T Porter
The factors influencing resiliency to the development of post-traumatic stress disorder (PTSD) remain to be elucidated. Clinical studies associate PTSD with polymorphisms of the FK506 binding protein 5 (FKBP5). However, it is unclear whether changes in FKBP5 expression alone could produce resiliency or susceptibility to PTSD-like symptoms. In this study, we used rats as an animal model to examine whether FKBP5 in the infralimbic (IL) or prelimbic (PL) medial prefrontal cortex regulates fear conditioning or extinction...
April 2017: Learning & Memory
https://www.readbyqxmd.com/read/28262266/ptsd-in-court-ii-risk-factors-endophenotypes-and-biological-underpinnings-in-ptsd
#14
REVIEW
Gerald Young
The second article in the series of three for the journal on "PTSD in Court" especially concerns the biological bases that have been found to be associated with PTSD (posttraumatic stress disorder). The cohering concepts in this section relate to risk factors; candidate genes; polygenetics; "gene×environment" interactions; epigenetics; endophenotypes; biomarkers; and connective networks both structurally and functionally (in terms of intrinsic connectivity networks, ICNs, including the DMN, SN, and CEN; that is, default mode, salience, and central executive networks, respectively)...
March 2, 2017: International Journal of Law and Psychiatry
https://www.readbyqxmd.com/read/28254433/loss-of-fkbp5-impedes-adipocyte-differentiation-under-both-normoxia-and-hypoxic-stress
#15
Lingling Zhang, Bin Qiu, Tingting Wang, Jun Wang, Ming Liu, Yuxue Xu, Chao Wang, Ran Deng, Kent Williams, Zhiwei Yang, Tiebing Liang, Weidong Yong
FK506-binding protein 51 (FKBP51) is one of the most important regulators in the GR-mediated stress response, and we previously demonstrated that loss of FKBP5 arrests adipogenesis and renders mice resistant to diet-induced obesity (DIO). However, the exact role of FKBP5 in the process of adipocyte differentiation under hypoxic conditions (the common microenvironment where adipocytes reside in obese individuals) is still unclear. Here, by isolating and culturing WT- and Fkbp5-knockout mouse embryonic fibroblasts (MEFs), and treat them at normal oxygen environment (21% O2, nomorxia) or low oxygen environment (5% O2, hypoxia)...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28247564/fkbp5-genotype-and-early-life-stress-exposure-predict-neurobehavioral-outcomes-for-preterm-infants
#16
Amy L D'Agata, Stephen Walsh, Dorothy Vittner, Xiaomei Cong, Jacqueline M McGrath, Erin E Young
PROBLEM: This study evaluated the relationship between stressful early life neonatal intensive care unit (NICU) experiences, genetic variation of a stress response-associated gene (FKBP5), and neurobehavioral outcomes. METHOD: The impact of genetic variation and stress experience on neurobehavioral outcomes was examined for 41 preterm infants. Statistical analyses explored the main effects of FKBP5 genotype and NICU stress experience, as well as their interaction on infant neurobehavioral development prior to discharge...
March 1, 2017: Developmental Psychobiology
https://www.readbyqxmd.com/read/28246044/dna-methylation-and-expression-of-stress-related-genes-in-pbmc-of-mdd-patients-with-and-without-serious-suicidal-ideation
#17
Bhaskar Roy, Richard C Shelton, Yogesh Dwivedi
Stress plays an important role in major depressive disorder (MDD) and is one of the state dependent factors in suicidal behavior. A dysfunctional hypothalamic-pituitary-adrenal axis is a common feature in this disorder. The involvement of environmental factors has added additional complexity to understanding depression or suicidal behavior. In this regard, epigenetic regulation has been considered a mechanistic interface between environmental stress stimuli and altered functioning of underlying gene network that may increase susceptibility to depression or suicidal behavior...
June 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28242321/functional-analysis-reveals-no-transcriptional-role-for-the-glucocorticoid-receptor-%C3%AE-isoform-in-zebrafish
#18
Antonia Chatzopoulou, Peter J Schoonheim, Vincenzo Torraca, Annemarie H Meijer, Herman P Spaink, Marcel J M Schaaf
In humans, two splice variants of the glucocorticoid receptor (GR) exist: the canonical α-isoform, and the β-isoform, which has been shown to have a dominant-negative effect on hGRα. Previously, we have established the occurrence of a GR β-isoform in zebrafish, and in the present study we have investigated the functional role of the zebrafish GRβ (zGRβ). Reporter assays in COS-1 cells demonstrated a dominant-negative effect of zGRβ but no such effect was observed in zebrafish PAC2 cells using induction of the fk506 binding protein 5 (fkbp5) gene as readout...
February 24, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28198448/influence-of-fkbp5-polymorphism-and-dna-methylation-on-structural-changes-of-the-brain-in-major-depressive-disorder
#19
Kyu-Man Han, Eunsoo Won, Youngbo Sim, June Kang, Changsu Han, Yong-Ku Kim, Seung-Hyun Kim, Sook-Haeng Joe, Min-Soo Lee, Woo-Suk Tae, Byung-Joo Ham
A single nucleotide polymorphism of rs1360780 in the FKBP5 gene is associated with a predisposition to developing major depressive disorder (MDD). We investigated the interactive effects of FKBP5 rs1360780 allelic variants, DNA methylation, and the diagnosis of MDD on structural changes of the entire brain. One hundred and fourteen patients with MDD and eighty-eight healthy controls underwent T1-weighted structural magnetic resonance imaging and FKBP5 rs1360780 genotyping, including DNA methylation of intron 7...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28135675/blunted-hpa-axis-activity-prior-to-suicide-attempt-and-increased-inflammation-in-attempters
#20
Nadine M Melhem, Sara Munroe, Anna Marsland, Katarina Gray, David Brent, Giovanna Porta, Antoine Douaihy, Mark L Laudenslager, Frank DePietro, Rasim Diler, Henry Driscoll, Priya Gopalan
BACKGROUND: Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation is associated with increased risk for suicidal behavior. However, it is not clear whether such dysregulation exists prior to or is a consequence of attempt. Studies also show an activation of inflammatory responses in suicidal behavior but often combine attempters with those with ideation. METHODS: The sample consisted of psychiatric inpatients, aged 15-30 years, admitted for suicide attempt (SA, n=38), inpatients admitted for suicidal ideation with no prior history of attempts (SI, n=40), and healthy controls (n=37)...
March 2017: Psychoneuroendocrinology
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