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Epigenetic and Autism

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https://www.readbyqxmd.com/read/28101829/autism-spectrum-disorders%C3%A2-diagnosis-and-management
#1
REVIEW
Sharmila Banerjee Mukherjee
Autism Spectrum Disorder (ASD) is a neuro-developmental disorder commonly seen in children. It is characterized by age inappropriate, impaired social communication and the presence of stereotypic behavior. This disorder is hypothesized to result from cerebral dysfunction arising from a complex interaction between genetic, epigenetic and environmental factors. ASD should be suspected in children failing ASD specific screening tests, in the presence of red flags in social, language and/or play domains, in children with developmental or language delay, abnormal behavior, poor school performance or in those who are at high risk...
January 19, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/28100736/methyl-cpg-binding-protein-mbd1-regulates-neuronal-lineage-commitment-through-maintaining-adult-neural-stem-cell-identity
#2
Emily M Jobe, Yu Gao, Brian E Eisinger, Janessa K Mladucky, Charles C Giuliani, Laurel E Kelnhofer, Xinyu Zhao
: Methyl-CpG-binding domain 1 (MBD1) belongs to a family of methyl-CpG-binding proteins that are epigenetic "readers" linking DNA methylation to transcriptional regulation. MBD1 is expressed in neural stem cells residing in the dentate gyrus of the adult hippocampus (aNSCs) and MBD1 deficiency leads to reduced neuronal differentiation, impaired neurogenesis, learning deficits, and autism-like behaviors in mice; however, the precise function of MBD1 in aNSCs remains unexplored. Here, we show that MBD1 is important for maintaining the integrity and stemness of NSCs, which is critical for their ability to generate neurons...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28068486/the-changing-epidemiology-of-autism-spectrum-disorders
#3
Kristen Lyall, Lisa Croen, Julie Daniels, M Daniele Fallin, Christine Ladd-Acosta, Brian K Lee, Bo Y Park, Nathaniel W Snyder, Diana Schendel, Heather E Volk, Gayle C Windham, Craig Newschaffer
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with lifelong impacts. Genetic and environmental factors contribute to ASD etiology, which remains incompletely understood. Research on ASD epidemiology has made significant advances in the past decade. Current prevalence is estimated to be at least 1.5% in developed countries, with recent increases primarily among those without comorbid intellectual disability. Genetic studies have identified a number of rare de novo mutations and gained footing in the areas of polygenic risk, epigenetics, and gene-by-environment interaction...
December 21, 2016: Annual Review of Public Health
https://www.readbyqxmd.com/read/28042663/all-our-sons-the-developmental-neurobiology-and-neuroendocrinology-of-boys-at-risk
#4
Allan N Schore
Why are boys at risk? To address this question, I use the perspective of regulation theory to offer a model of the deeper psychoneurobiological mechanisms that underlie the vulnerability of the developing male. The central thesis of this work dictates that significant gender differences are seen between male and female social and emotional functions in the earliest stages of development, and that these result from not only differences in sex hormones and social experiences but also in rates of male and female brain maturation, specifically in the early developing right brain...
January 2017: Infant Mental Health Journal
https://www.readbyqxmd.com/read/28042538/rora-and-autism-in-the-isfahan-population-is-there-an-epigenetic-relationship
#5
Mansoor Salehi, Elahe Kamali, Mojgan Karahmadi, Seyyed Mohammad Mousavi
OBJECTIVE: Autism is a neurodevelopmental disorder characterized by difficulty in verbal and non-verbal communication, impaired social interaction, and restricted and repetitive behavior. It has been recently introduced as a multigenic disorder with significant epigenetic effects on its pathology. Recently, epigenetic silencing of retinoic acid receptor- related orphan receptor alpha (RORα) gene (which has an essential role in neural tissue development) was shown to have occurred in autistic children due to methylation of its promoter region...
2017: Cell Journal
https://www.readbyqxmd.com/read/28032673/dental-pulp-stem-cells-model-early-life-and-imprinted-dna-methylation-patterns
#6
Keith Dunaway, Sarita Goorha, Lauren Matelski, Nora Urraca, Pamela J Lein, Ian Korf, Lawrence T Reiter, Janine M LaSalle
Early embryonic stages of pluripotency are modeled for epigenomic studies primarily with human embryonic stem cells (ESC) or induced pluripotent stem cells (iPSCs). For analysis of DNA methylation however, ESCs and iPSCs do not accurately reflect the DNA methylation levels found in preimplantation embryos. Whole genome bisulfite sequencing (WGBS) approaches have revealed the presence of large partially methylated domains (PMDs) covering 30%-40% of the genome in oocytes, preimplantation embryos, and placenta...
December 29, 2016: Stem Cells
https://www.readbyqxmd.com/read/28032018/a-multi-target-small-molecule-for-targeted-transcriptional-activation-of-therapeutically-significant-nervous-system-genes
#7
Yulei Wei, Ganesh N Pandian, Tingting Zou, Junichi Taniguchi, Shinsuke Sato, Gengo Kashiwazaki, Thangavel Vaijayanthi, Takuya Hidaka, Toshikazu Bando, Hiroshi Sugiyama
An integrated multi-target small molecule capable of altering dynamic epigenetic and transcription programs associated with the brain and nervous system has versatile applications in the regulation of therapeutic and cell-fate genes. Recently, we have been constructing targeted epigenetic ON switches by integrating sequence-specific DNA binding pyrrole-imidazole polyamides with a potent histone deacetylase inhibitor SAHA. Here, we identified a DNA-based epigenetic ON switch termed SAHA-L as the first-ever multi-target small molecule capable of inducing transcription programs associated with the human neural system and brain synapses networks in BJ human foreskin fibroblasts and 201B7-iPS cells...
December 2016: ChemistryOpen
https://www.readbyqxmd.com/read/28018572/placental-methylome-analysis-from-a-prospective-autism-study
#8
Diane I Schroeder, Rebecca J Schmidt, Florence K Crary-Dooley, Cheryl K Walker, Sally Ozonoff, Daniel J Tancredi, Irva Hertz-Picciotto, Janine M LaSalle
BACKGROUND: Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders that are behaviorally diagnosed in early childhood. Most ASD cases likely arise from a complex mixture of genetic and environmental factors, an interface where the epigenetic marks of DNA methylation may be useful as risk biomarkers. The placenta is a potentially useful surrogate tissue characterized by a methylation pattern of partially methylated domains (PMDs) and highly methylated domains (HMDs) reflective of methylation patterns observed in the early embryo...
2016: Molecular Autism
https://www.readbyqxmd.com/read/27920144/methyl-cpg-binding-protein-mbd1-regulates-neuronal-lineage-commitment-through-maintaining-adult-neural-stem-cell-identity
#9
Emily M Jobe, Yu Gao, Brian E Eisinger, Janessa K Mladucky, Charles C Giuliani, Laurel E Kelnhofer, Xinyu Zhao
: MBD1 belongs to a family of methyl-CpG binding proteins that are epigenetic "readers", linking DNA methylation to transcriptional regulation. MBD1 is expressed in neural stem cells residing in the dentate gyrus of the adult hippocampus (aNSCs), and MBD1 deficiency leads to reduced neuronal differentiation, impaired neurogenesis, learning deficits, and autism-like behaviors in mice; however the precise function of MBD1 in aNSCs remains unexplored. Here, we show that MBD1 is important for maintaining the integrity and stemness of NSCs, which is critical for their ability to generate neurons...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27919711/epigenetic-dysfunctional-diseases-and-therapy-for-infection-and-inflammation
#10
REVIEW
Saheli Samanta, Sheeja Rajasingh, Thuy Cao, Buddhadeb Dawn, Johnson Rajasingh
Even though the discovery of the term 'epigenetics' was in the 1940s, it has recently become one of the most promising and expanding fields to unravel the gene expression pattern in several diseases. The most well studied example is cancer, but other diseases like metabolic disorders, autism, or inflammation-associated diseases such as lung injury, autoimmune disease, asthma, and type-2 diabetes display aberrant gene expression and epigenetic regulation during their occurrence. The change in the epigenetic pattern of a gene may also alter gene function because of a change in the DNA status...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27881780/negative-allosteric-modulation-of-mglur5-partially-corrects-pathophysiology-in-a-mouse-model-of-rett-syndrome
#11
Jifang Tao, Hao Wu, Amanda A Coronado, Elizabeth de Laittre, Emily K Osterweil, Yi Zhang, Mark F Bear
: Rett syndrome (RTT) is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2), an epigenetic regulator of mRNA transcription. Here, we report a test of the hypothesis of shared pathophysiology of RTT and fragile X, another monogenic cause of autism and intellectual disability. In fragile X, the loss of the mRNA translational repressor FMRP leads to exaggerated protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5). We found that mGluR5- and protein-synthesis-dependent synaptic plasticity were similarly altered in area CA1 of Mecp2 KO mice...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27845777/newer-insights-into-the-role-of-mirna-a-tiny-genetic-tool-in-psychiatric-disorders-focus-on-post-traumatic-stress-disorder
#12
REVIEW
V V Giridharan, R A Thandavarayan, G R Fries, C Walss-Bass, T Barichello, N J Justice, M K Reddy, J Quevedo
Post-traumatic stress disorder (PTSD) is a mental disorder occurring in about 2-9% of individuals after their exposure to life-threatening events, such as severe accidents, sexual abuse, combat or a natural catastrophe. Because PTSD patients are exposed to trauma, it is likely that epigenetic modifications have an important role in disease development and prognosis. For the past two decades, abnormal expression of the epigenetic regulators microRNAs (miRs) and miR-mediated gene regulation have been given importance in a variety of human diseases, such as cancer, heart disease and viral infection...
November 15, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27825935/genetic-control-of-social-behavior-lessons-from-mutant-mice
#13
Giovanni Provenzano, Gabriele Chelini, Yuri Bozzi
Social behavior is evolutionary conserved, and is thought to be evolved since it increased reproductive and survival fitness of living species. In humans, disturbances of social behavior are a peculiar pathological trait of neurodevelopmental disorders, namely autism spectrum disorder (ASD). ASD is defined by deficits in two core domains (social interaction/communication and repetitive/restrictive behaviors), which emerge during early postnatal development. ASD has a strong genetic component: copy number variations, de novo and familial mutations, as well as epigenetic modifications have been reported in a huge number of genes...
November 4, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27819277/the-transgenerational-inheritance-of-autism-like-phenotypes-in-mice-exposed-to-valproic-acid-during-pregnancy
#14
Chang Soon Choi, Edson Luck Gonzales, Ki Chan Kim, Sung Min Yang, Ji-Woon Kim, Darine Froy Mabunga, Jae Hoon Cheong, Seol-Heui Han, Geon Ho Bahn, Chan Young Shin
Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27816931/underlying-role-of-mitochondrial-mutagenesis-in-the-pathogenesis-of-a-disease-and-current-approaches-for-translational-research
#15
Maria Paraskevaidi, Pierre L Martin-Hirsch, Maria Kyrgiou, Francis L Martin
Mitochondrial diseases have been extensively investigated over the last three decades, but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases but also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat, as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease...
November 5, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27814400/sperm-microrna-content-is-altered-in-a-mouse-model-of-male-obesity-but-the-same-suite-of-micrornas-are-not-altered-in-offspring-s-sperm
#16
Tod Fullston, E Maria C Ohlsson-Teague, Cristin G Print, Lauren Y Sandeman, Michelle Lane
The prevalence of obesity is increasing worldwide and has tripled in men of reproductive age since the 1970s. Concerningly, obesity is not only comorbid with other chronic diseases, but there is mounting evidence that it increases the non-communicable disease load in their children (eg mortality, obesity, autism). Animal studies have demonstrated that paternal obesity increases the risk of metabolic (eg glucose metabolism defects, obesity) and reproductive disorders in offspring. Epigenetic changes within sperm are clear mechanistic candidates that are associated with both changes to the father's environment and offspring phenotype...
2016: PloS One
https://www.readbyqxmd.com/read/27797829/genome-wide-transcriptional-profiling-and-structural-magnetic-resonance-imaging-in-the-maternal-immune-activation-model-of-neurodevelopmental-disorders
#17
Juliet Richetto, Robert Chesters, Annamaria Cattaneo, Marie A Labouesse, Ana Maria Carrillo Gutierrez, Tobias C Wood, Alessia Luoni, Urs Meyer, Anthony Vernon, Marco A Riva
Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, including schizophrenia and autism. The molecular processes underlying this pathological association, however, are only partially understood. Here, we combined unbiased genome-wide transcriptional profiling with follow-up epigenetic analyses and structural magnetic resonance imaging to explore convergent molecular and neuromorphological alterations in corticostriatal areas of adult offspring exposed to prenatal immune activation...
October 23, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27785696/environmental-induction-of-neurodevelopmental-disorders
#18
Rodrick Wallace
Chemical exposures, pre- and neonatal infections, psychosocial stress, and the cross-generational cultural and epigenetic impacts of these and other toxicants become an integrated, sometimes synergistic, signal that can overwhelm essential neurodevelopmental regulation. We characterize that dynamic through statistical models based on the asymptotic limit theorems of control and information theories. Schizophrenia and autism emerge as two different 'phases' of pathological neurodevelopmental 'condensations' that impair the dynamic, shifting global workspace of normal mental function...
October 26, 2016: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/27770494/paternal-age-and-psychiatric-disorders-a-review
#19
Hilde de Kluiver, Jacobine E Buizer-Voskamp, Conor V Dolan, Dorret I Boomsma
We review the hypotheses concerning the association between the paternal age at childbearing and childhood psychiatric disorders (autism spectrum- and attention deficit/hyperactive disorder) and adult disorders (schizophrenia, bipolar-, obsessive-compulsive-, and major depressive disorder) based on epidemiological studies. Several hypotheses have been proposed to explain the paternal age effect. We discuss the four main-not mutually exclusive-hypotheses. These are the de novo mutation hypothesis, the hypothesis concerning epigenetic alterations, the selection into late fatherhood hypothesis, and the environmental resource hypothesis...
October 22, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27748930/mirnas-and-their-role-in-the-correlation-between-schizophrenia-and-cancer-review
#20
E Rizos, N Siafakas, E Skourti, C Papageorgiou, J Tsoporis, T H Parker, D I Christodoulou, D A Spandidos, E Katsantoni, V Zoumpourlis
Schizophrenia (SZ) and cancer (Ca) have a broad spectrum of clinical phenotypes and a complex biological background, implicating a large number of genetic and epigenetic factors. SZ is a chronic neurodevelopmental disorder signified by an increase in the expression of apoptotic molecular signals, whereas Ca is conversely characterized by an increase in appropriate molecular signaling that stimulates uncontrolled cell proliferation. The rather low risk of developing Ca in patients suffering from SZ is a hypothesis that is still under debate...
December 2016: Molecular Medicine Reports
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