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Programmatic Research on Fetal Alcohol Spectrum Disorder (FASD)

Programmatic Research on Fetal Alcohol Spectrum Disorder (FASD). Presentation to the Child Health Signature Research Program Group February 21, 2008. Daniel Savage, Ph.D. Regents’ Professor & Chair Department of Neurosciences, UNM SOM 505-272-8808 dsavage@salud.unm.edu.

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Programmatic Research on Fetal Alcohol Spectrum Disorder (FASD)

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  1. Programmatic Research on Fetal Alcohol Spectrum Disorder (FASD) Presentation to the Child Health Signature Research Program Group February 21, 2008 Daniel Savage, Ph.D. Regents’ Professor & Chair Department of Neurosciences, UNM SOM 505-272-8808 dsavage@salud.unm.edu

  2. Fetal Alcohol Spectrum Disorder ( FASD ) Physical Defects FAS ~ 0.03% FAE / ARBD ~ 0.15% Alcohol-Related Neurodevelopmental Disorder (ARND) > 1% Functional Deficits

  3. Long-Term Research Objectives • Understand the neurobiologic bases of fetal ethanol-induced deficits in synaptic plasticity and learning. • Identify therapeutic agents that ameliorate fetal ethanol-induced deficits in synaptic plasticity and learning. • Establish combined neurobehavioral and functional neuroimaging approaches for: • Diagnosis of fetal ethanol-associated brain and behavioral deficits and, • Monitoring / predicting the efficacy of various behavioral and pharmacotherapeutic agents. • Identify a sensitive and specific biomarker system predictive of adverse neurobehavioral outcomes in fetal ethanol-exposed offspring.

  4. 2. Identify therapeutic agents that ameliorate fetal ethanol- induced synaptic plasticity & learning deficits. (R21 AA16619) Concept: Use of our moderate ethanol exposure paradigm as a screen for identifying therapeutic agents for treating cognitive deficits associated with prenatal ethanol exposure. Approach: “Proof of Concept” proposal to study one cognition-enhancing agent, a selective H3 receptor antagonist ABT-239. One-trial Contextual Fear Conditioning Four-day Retention of Platform Location

  5. 3. Neurobehavioral and functional neuroimaging characterization of learning deficits in subjects with FASD (MIND C-2018) Virtual Morris Water Task Volumetrics Spectroscopy Phase II: Probe Trial MEG Control: 6 / 7 FAS: 1 / 7

  6. 4. A biomarker system for predicting adverse neurobehavioral outcomes in fetal ethanol-exposed offspring. (R21 AA15420) • Employ our moderate prenatal ethanol exposure paradigm to examine ethanol-induced alterations in placental protein expression using proteomic and genomic approaches. • 302 genes (0.13% of all genes) were altered greater than two-fold by moderate maternal ethanol consumption • Genes whose proteins associated with cytoskeletal, metabolic, endocrine, immune or neural function are altered. Follow-up Studies: 1. “Sensitivity Studies”Ethanol Dose Window of detectability 2. “Specificity Studies” Other risk factor impact Preclinical Clinical Placental Proteomics Placental Proteomics Fetal Brain Proteomics Weanling Behaviors & Neurophysiology Infant Behaviors & Neurophysiology

  7. Fetal ethanol-induced behavioral deficits: Mechanisms, diagnoses and interventions Developmental Alcohol Research Center - P20 • Preclinical Projects: • Epigenetics of FASD • Stem Cells • Cognition Enhancers • Predisposition to PTSD • Biomarkers Diagnosis / Prognosis • Preclinical Investigators: Allan, Caldwell, Cunningham, Hamilton, Perrone-Bizzozero, Savage, Valenzuela, Zhao • Clinical Projects: • Information Processing • Infant Sensory Integration (baby MEG) • Behavioral Intervention & Functional Neuroimaging • Clinical investigators: Kodituwakku, Verney, Stephen, Tesche, Kiehl, May, Rayburn, Weisend Combines basic, clinical and translational science across HSC, Main Campus and MIND

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