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Epigenetic and Autism

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https://www.readbyqxmd.com/read/28608855/mice-lacking-the-chromodomain-helicase-dna-binding-5-chromatin-remodeler-display-autism-like-characteristics
#1
M T Pisansky, A E Young, M B O'Connor, I I Gottesman, A Bagchi, J C Gewirtz
Although autism spectrum disorders (ASDs) share a core set of nosological features, they exhibit substantial genetic heterogeneity. A parsimonious hypothesis posits that dysregulated epigenetic mechanisms represent common pathways in the etiology of ASDs. To investigate this hypothesis, we generated a novel mouse model resulting from brain-specific deletion of chromodomain helicase DNA-binding 5 (Chd5), a chromatin remodeling protein known to regulate neuronal differentiation and a member of a gene family strongly implicated in ASDs...
June 13, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28608249/retinoic-acid-related-orphan-receptor-alpha-rora-variants-are-associated-with-autism-spectrum-disorder
#2
Arezou Sayad, Rezvan Noroozi, Mir Davood Omrani, Mohammad Taheri, Soudeh Ghafouri-Fard
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with various epidemiologic, genetic, epigenetic, and environmental factors being associated with it. The observed sex bias in ASD towards male has prompted investigators to propose sex-dependent mechanisms for ASD. Retinoic acid-related orphan receptor-alpha (RORA) is a new autism candidate gene that has been shown to be differentially regulated by male and female hormones. Previous studies have shown deregulation of its expression in the prefrontal cortex and the cerebellum of ASD patients...
June 12, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28598237/homocysteine-as-a-diagnostic-and-etiopathogenic-factor-in-children-with-autism-spectrum-disorder
#3
Jan Józefczuk, Wiktoria Kasprzycka, Rafał Czarnecki, Alfreda Graczyk, Paweł Józefczuk, Krzysztof Magda, Urszula Lampart
Substantial characteristics of autism are cognitive and psychophysical disorders. Etiopathogenetic factors are thought to be responsible for development of autism in children with genetic predisposition as well as have their effect on the severity of the disorders. The main problem of early identification of patients affected by autism spectrum disorder is that there are no clear diagnostic criteria. The aim of our study was assessment of hair magnesium and serum homocysteine concentrations in children with autism...
June 9, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28567415/neurodevelopmental-disorders-and-environmental-toxicants-epigenetics-as-an-underlying-mechanism
#4
REVIEW
Nguyen Quoc Vuong Tran, Kunio Miyake
The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28551756/extracerebral-dysfunction-in-animal-models-of-autism-spectrum-disorder
#5
Elisa L Hill-Yardin, Sonja J McKeown, Gaia Novarino, Andreas M Grabrucker
Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28538662/maternal-factors-that-induce-epigenetic-changes-contribute-to-neurological-disorders-in-offspring
#6
REVIEW
Avijit Banik, Deepika Kandilya, Seshadri Ramya, Walter Stünkel, Yap Seng Chong, S Thameem Dheen
It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down's syndrome, Rett syndrome, and later onset of neuropsychological deficits...
May 24, 2017: Genes
https://www.readbyqxmd.com/read/28534818/a-review-of-the-impact-of-maternal-obesity-on-the-cognitive-function-and-mental-health-of-the-offspring
#7
REVIEW
Laura Contu, Cheryl A Hawkes
Globally, more than 20% of women of reproductive age are currently estimated to be obese. Children born to obese mothers are at higher risk of developing obesity, coronary heart disease, diabetes, stroke, and asthma in adulthood. Increasing clinical and experimental evidence suggests that maternal obesity also affects the health and function of the offspring brain across the lifespan. This review summarizes the current findings from human and animal studies that detail the impact of maternal obesity on aspects of learning, memory, motivation, affective disorders, attention-deficit hyperactivity disorder, autism spectrum disorders, and neurodegeneration in the offspring...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28531286/is-foetal-hyperexposure-to-androgens-a-cause-of-pcos
#8
Panagiota Filippou, Roy Homburg
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. The pathophysiology of this syndrome is still not completely understood but recent evidence suggests that the intra-uterine environment may be a key factor in the pathogenesis of PCOS, in particular, hyperexposure of the foetus to androgens. High concentrations of maternal serum testosterone during pregnancy have been shown to influence behaviour during childhood, the prevalence of autism disorders and anti-Mullerian hormone (AMH) concentrations in adolescence...
May 20, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/28523541/epigenetics-of-autism-spectrum-disorder
#9
Michelle T Siu, Rosanna Weksberg
Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children. ASD is incredibly heterogeneous both clinically and aetiologically. The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors. Normal epigenetic marks modifiable by both genetics and environmental exposures can result in epigenetic alterations that disrupt the regulation of gene expression, negatively impacting biological pathways important for brain development...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28504324/electromagnetic-fields-pulsed-radiofrequency-radiation-and-epigenetics-how-wireless-technologies-may-affect-childhood-development
#10
Cindy Sage, Ernesto Burgio
Mobile phones and other wireless devices that produce electromagnetic fields (EMF) and pulsed radiofrequency radiation (RFR) are widely documented to cause potentially harmful health impacts that can be detrimental to young people. New epigenetic studies are profiled in this review to account for some neurodevelopmental and neurobehavioral changes due to exposure to wireless technologies. Symptoms of retarded memory, learning, cognition, attention, and behavioral problems have been reported in numerous studies and are similarly manifested in autism and attention deficit hyperactivity disorders, as a result of EMF and RFR exposures where both epigenetic drivers and genetic (DNA) damage are likely contributors...
May 15, 2017: Child Development
https://www.readbyqxmd.com/read/28500650/aberrant-cognitive-phenotypes-and-altered-hippocampal-bdnf-expression-related-to-epigenetic-modifications-in-mice-lacking-the-post-synaptic-scaffolding-protein-shank1-implications-for-autism-spectrum-disorder
#11
A Özge Sungur, Magdalena C E Jochner, Hani Harb, Ayşe Kılıç, Holger Garn, Rainer K W Schwarting, Markus Wöhr
Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by persistent deficits in social communication/interaction, together with restricted/repetitive patterns of behavior. ASD is among the most heritable neuropsychiatric conditions, and while available evidence points to a complex set of genetic factors, the SHANK gene family has emerged as one of the most promising candidates. Here, we assessed ASD-related phenotypes with particular emphasis on social behavior and cognition in Shank1 mouse mutants in comparison to heterozygous and wildtype littermate controls across development in both sexes...
May 12, 2017: Hippocampus
https://www.readbyqxmd.com/read/28495514/neurobehavioral-risks-of-ssris-in-pregnancy-comparing-human-and-animal-data
#12
REVIEW
Asher Ornoy
During the last twenty years, in spite of extensive literature regarding the use of SSRIs in pregnancy, confusion still exists as to possible long-term risks of these drugs on the offspring. Possible negative effects relate to neurodevelopmental outcome and association with Autism Spectrum Disorder (ASD). Most neurodevelopmental follow up studies did not find significant cognitive impairment except from some apparently transient, gross motor delay and slight impairment of language abilities. The literature on the possible association of SSRIs with ASD is inconsistent, and if an association exists it is apparently throughout pregnancy...
May 8, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28472621/the-valproic-acid-induced-rodent-model-of-autism
#13
REVIEW
Chiara Nicolini, Margaret Fahnestock
Autism is a lifelong neurodevelopmental disorder characterized by impairments in social communication and interaction and by repetitive patterns of behavior, interests and activities. While autism has a strong genetic component, environmental factors including toxins, pesticides, infection and drugs are known to confer autism susceptibility, likely by inducing epigenetic changes. In particular, exposure to valproic acid (VPA) during pregnancy has been demonstrated to increase the risk of autism in children...
May 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28465421/hyperactive-locomotion-in-a-drosophila-model-is-a-functional-readout-for-the-synaptic-abnormalities-underlying-fragile-x-syndrome
#14
Risa Kashima, Patrick L Redmond, Prajakta Ghatpande, Sougata Roy, Thomas B Kornberg, Thomas Hanke, Stefan Knapp, Giorgio Lagna, Akiko Hata
Fragile X syndrome (FXS) is the most common cause of heritable intellectual disability and autism and affects ~1 in 4000 males and 1 in 8000 females. The discovery of effective treatments for FXS has been hampered by the lack of effective animal models and phenotypic readouts for drug screening. FXS ensues from the epigenetic silencing or loss-of-function mutation of the fragile X mental retardation 1 (FMR1) gene, which encodes an RNA binding protein that associates with and represses the translation of target mRNAs...
May 2, 2017: Science Signaling
https://www.readbyqxmd.com/read/28463237/epigenetic-and-transgenerational-mechanisms-in-infection-mediated-neurodevelopmental-disorders
#15
REVIEW
U Weber-Stadlbauer
Prenatal infection is an environmental risk factor for various brain disorders with neurodevelopmental components, including autism spectrum disorder and schizophrenia. Modeling this association in animals shows that maternal immune activation negatively affects fetal brain development and leads to the emergence of behavioral disturbances later in life. Recent discoveries in these preclinical models suggest that epigenetic modifications may be a critical molecular mechanism by which prenatal immune activation can mediate changes in brain development and functions, even across generations...
May 2, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28439102/mecp2-regulated-mirnas-control-early-human-neurogenesis-through-differential-effects-on-erk-and-akt-signaling
#16
N Mellios, D A Feldman, S D Sheridan, J P K Ip, S Kwok, S K Amoah, B Rosen, B A Rodriguez, B Crawford, R Swaminathan, S Chou, Y Li, M Ziats, C Ernst, R Jaenisch, S J Haggarty, M Sur
Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28384108/profiling-of-circulating-serum-micrornas-in-children-with-autism-spectrum-disorder-using-stem-loop-qrt-pcr-assay
#17
Tatyana M Kichukova, Nikolay T Popov, Ivan S Ivanov, Tihomir I Vachev
BACKGROUND: Development of biomarkers for autism spectrum disorder (ASD) has still remained a challenge to date. Recently, alterations of the expression of microRNAs (miRNAs) in peripheral blood, serum and post-mortem brain tissue have been linked to ASD. miRNAs are known to be secreted by various cell types and can mediate transmission of information into recipient cells and to modulate their physiological functions. On this basis it is assumed that circulating miRNAs could be useful biomarkers for the diagnosis or prognosis of pathological conditions...
March 1, 2017: Folia Medica
https://www.readbyqxmd.com/read/28372995/targeting-aggression-in-severe-mental-illness-the-predictive-role-of-genetic-epigenetic-and-metabolomic-markers
#18
REVIEW
Mirko Manchia, Vassilios Fanos
Human aggression is a complex and widespread social behavior that is overrepresented in individuals affected by severe mental illness (SMI), such as schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). A substantial proportion of the liability threshold for aggressive behavior is determined by genetic factors, and environmental moderators might precipitate the manifestation of this behavioral phenotype through modification of gene expression via the epigenetic machinery...
July 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28361099/a-de-novo-splice-site-mutation-in-ehmt1-resulting-in-kleefstra-syndrome-with-pharmacogenomics-screening-and-behavior-therapy-for-regressive-behaviors
#19
Amit Kumar Mitra, Jessica Dodge, Jody Van Ness, Israel Sokeye, Brian Van Ness
BACKGROUND: Kleefstra syndrome (KS) is a rare autosomal dominant developmental disability, caused by microdeletions or intragenic mutations within the epigenetic regulator gene EHMT1 (euchromatic histone lysine N-methyltransferase 1). In addition to common features of autism, young adult regressive behaviors have been reported. However, the genetic downstream effects of the reported deletions or mutations on KS phenotype have not yet been completely explored. While genetic backgrounds affecting drug metabolism can have a profound effect on therapeutic interventions, pharmacogenomic variations are seldom considered in directing psychotropic therapies...
March 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28335457/the-epigenetic-link-between-prenatal-adverse-environments-and-neurodevelopmental-disorders
#20
REVIEW
Marija Kundakovic, Ivana Jaric
Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf)...
March 18, 2017: Genes
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