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Maternal alcohol abuse during pregnancy can result in a range of structural and functional abnormalities that include lifelong physical, mental, behavioral and learning disabilities, now collectively termed as Fetal Alcohol Spectrum Disorders (FASD). The incidence of FASD is now estimated be as high as 10 per 1000 live births. Each year, 40,000 babies are born with FASD in the United States at an estimated cost of $1.4 million per individual and total cost of $6 billion. Because of the magnitude of this problem and because the incidence has not decreased in spite intensive efforts to educate women to not abuse alcohol during pregnancy, ways to prevent or mitigate the effects of prenatal alcohol exposure must be explored in addition to education. Therefore, we wished to identify the precise mechanisms by which alcohol mediates the neurodevelopmental damage in order to develop intervention/amelioration strategies. The present study was conducted using an ovine model system. The large body mass of the ovine fetus, the longer gestation that is more similar to that of humans, and that all three trimester equivalents occur in utero, make the sheep an excellent model to study the effects of alcohol on the developing fetus. Our study establishes that maternal alcohol exposure does not result in fetal cerebral hypoxia. Instead, alcohol results in hypercapnea and acidemia leading to a cascade of events in the maternal and fetal compartments that include deficits in the levels of glutamine and glutamine-related amino acids, alterations in endocrine axes, oxidative stress, alteration in cardiovascular homeostasis and fetal neuronal loss. Further, we demonstrate that inhibiting the novel two-pore domain acid sensitive potassium channel (TASK) expressed in the cerebellar granule cells and the peripheral and central chemoreceptors may prove to a be potential therapeutic strategy. Preventive strategies that are safe to use in pregnant women and that involve glutamine-related pathways are also suggested. Finally, the study also establishes the beneficial effects of moderate alcohol consumption on the fetal skeletal system.
This volume provides current state-of-the-art methods for screening, diagnosis, management, and prevention of fetal alcohol spectrum disorder (and FASD). Chapters detail animal models, mechanism of ethanol teratogenesis, genetic mechanisms, clinical perspectives, physical traits in children with FASD, managing behavior, FASD and the correction system, nutritional influences aiding FASD prevention, prenatal alcohol screening, the use of dental signatures in FASD diagnosis, the experiences of FASD research and clinical practices in Australia, Canada, UK, USA, adult FASD diagnosis, FASD and children in care, FASD and the healing journey. Authoritative and cutting-edge, Advances in Fetal Alcohol Spectrum Disorder aims to be a useful practical guide to researchers and clinicians to help further their study in this field.
Recognition of the relationship between alcohol abuse and adverse prenatal outcomes is reflected in the warning labels on every alcoholic beverage sold in the United States. Because alcohol abuse has serious consequences for both individuals and society as a whole, much research has been devoted to this problem. Fetal Alcohol Syndrome provides straightforward facts regarding the impact of alcohol consumption as it affects the development of the embryo and fetus. Surveying current research of fetal alcohol syndrome and its related problems, the book addresses the immediate effects on development at various stages. Long-term action of prenatal alcohol exposure later in life is also considered. A chapter devoted to assessing the behavior of children who were prenatally exposed to alcohol emphasizes the necessity of longitudinal studies of fetal alcohol syndrome. This important reference offers a thorough overview of a problem that cannot be ignored.
Women drinking during pregnancy can result in Fetal Alcohol Spectrum Disorder (FASD), which may feature variable neurodevelopmental deficits, facial dysmorphology, growth retardation, and learning disabilities. Research suggests the human brain is precisely formed through an intrinsic, genetic-cellular expression that is carefully orchestrated by an epigenetic program. This program can be influenced by environmental inputs such as alcohol. Current research suggests the genetic and epigenetic elements of FASD are heavily intertwined and highly dependent on one another. As such, now is the time for investigators to combine genetic, genomic and epigenetic components of alcohol research into a centralized, accessible platform for discussion. Genetic analyses inform gene sets which may be vulnerable to alcohol exposure during early neurulation. Prenatal alcohol exposure indeed alters expression of gene subsets, including genes involved in neural specification, hematopoiesis, methylation, chromatin remodeling, histone variants, eye and heart development. Recently, quantitative genomic mapping has revealed loci (QTLs) that mediate alcohol-induced phenotypes identified between two alcohol-drinking mouse strains. One question to consider is (besides the role of dose and stage of alcohol exposure) why only 5% of drinking women deliver newborns diagnosed with FAS (Fetal Alcohol Syndrome)? Studies are ongoing to answer this question by characterizing genome-wide expression, allele-specific expression (ASE), gene polymorphisms (SNPs) and maternal genetic factors that influence alcohol vulnerability. Alcohol exposure during pregnancy, which can lead to FASD, has been used as a model to resolve the epigenetic pathway between environment and phenotype. Epigenetic mechanisms modify genetic outputs through alteration of 3D chromatin structure and accessibility of transcriptional machinery. Several laboratories have reported altered epigenetics, including DNA methylation and histone modification, in multiple models of FASD. During development DNA methylation is dynamic yet orchestrated in a precise spatiotemporal manner during neurulation and coincidental with neural differentiation. Alcohol can directly influence epigenetics through alterations of the methionine pathway and subsequent DNA or histone methylation/acetylation. Alcohol also alters noncoding RNA including miRNA and transposable elements (TEs). Evidence suggests that miRNA expression may mediate ethanol teratology, and TEs may be affected by alcohol through the alteration of DNA methylation at its regulatory region. In this manner, the epigenetic and genetic components of FASD are revealing themselves to be mechanistically intertwined. Can alcohol-induced epigenomic alterations be passed across generations? Early epidemiological studies have revealed infants with FASD-like features in the absence of maternal alcohol, where the fathers were alcoholics. Novel mechanisms for alcohol-induced phenotypes include altered sperm DNA methylation, hypomethylated paternal allele and heritable epimutations. These studies predict the heritability of alcohol-induced epigenetic abnormalities and gene functionality across generations. We opened a forum to researchers and investigators the field of FASD to discuss their insights, hypotheses, fresh data, past research, and future research themes embedded in this rising field of the genetics and epigenetics of FASD. This eBook is a product of the collective sharing and debate among researchers who have contributed or reviewed each subject.
The Novartis Foundation Series is a popular collection of the proceedings from Novartis Foundation Symposia, in which groups of leading scientists from a range of topics across biology, chemistry and medicine assembled to present papers and discuss results. The Novartis Foundation, originally known as the Ciba Foundation, is well known to scientists and clinicians around the world.
First published in 2003. Children's Friendship Training is a complete manualized guide for therapists treating children with peer problems. This unique, empirically validated treatment is the first to integrate parents into the therapy process to ensure generalization to school and home. Representing over twelve years of research, Children's Friendship Training presents the comprehensive social skills training program developed by these pioneering authors. Step-by-step interventions help children develop the skills to initiate mutually satisfying social interactions. These interactions can lead to higher regard within the peer group and the development of satisfying dyadic relationships that will, in turn, serve to enhance overall well being. Clinical and empirical rationales, illustrative case examples and parent handouts that educate parents and give specific guidelines for homework assignments are presented for each treatment module. Brief relevant reviews of the child development literature and selective reviews of assessment techniques and other approached to children's social skills training are presented to sufficiently acquaint therapists interested in implementing children's friendship training.
This eBook addresses the impact of prenatal exposure to alcohol, and Fetal Alcohol Spectrum Disorders (FASD). It presents a compilation of current research by leading experts in the field and serves as a guide to future directions in FASD research, interventions and treatment. the book includes a comprehensive compendium of our knowledge of the dangers of prenatal alcohol exposure and covers ways to screen and intervene with pregnant women, diagnosis and treatment to ameliorate the effects of prenatal alcohol exposure (through the lifespan), and other related issues, such as building a state infrastructure of health services and legislation. the eBook is intended as a textbook for graduate courses relevant to FASD.
Alcohol is the most widely used drug in the world, yet alcoholism remains a serious addiction affecting nearly 20 million Americans. Our current understanding of alcohol's effect on brain structure and related functional damage is being revolutionized by genetic research, basic neuroscience, brain imaging science, and systematic study of cognitive, sensory, and motor abilities. Volume 125 of the Handbook of Clinical Neurology is a comprehensive, in-depth treatise of studies on alcohol and the brain covering the basic understanding of alcohol's effect on the central nervous system, the diagnosis and treatment of alcoholism, and prospect for recovery. The chapters within will be of interest to clinical neurologists, neuropsychologists, and researchers in all facets and levels of the neuroscience of alcohol and alcoholism. The first focused reference specifically on alcohol and the brain Details our current understanding of how alcohol impacts the central nervous system Covers clinical and social impact of alcohol abuse disorders and the biomedical consequences of alcohol abuse Includes section on neuroimaging of neurochemical markers and brain function