Mouse Model Neuro-Facial Dysmorphology: Tanslational and Treatment Studies

Project: Research project

Description

DESCRIPTION (provided by applicant): Fetal alcohol syndrome (FAS) occurs in children born to women who drink alcohol heavily during pregnancy and is one of the leading non-hereditary causes of mental retardation in the Western World. It is estimated that the prevalence of FAS in the general U.S. population is between 0.5 and 2.0 per 1,000 births, while the undiagnosed population with variable facial and brain dysmorphology described as fetal alcohol spectrum disorder (FASD) is estimated to be 10 times higher. The difficulty in the diagnosis of FASD involves misdiagnosis due to the presence or absence of the typical facial dysmorphology in association with brain dysfunction. Accurate diagnosis is further complicated by the lack of information about the contribution of dose, frequency, and timing of alcohol exposure during pregnancy to variation in facial dysmorphology. In this project, a mouse model that models human consumption and is known to produce FAS-like features resulting from prenatal alcohol exposure, will be used to test the effects of differences in dose and timing of alcohol exposure on face and brain development. A combination of 3D imaging that includes Micro-video and micro-resonance imaging (MRI) will be used to capture the detailed facial structure, micro-computational tomography (Micro-CT) to capture the underlying facial bone, MRI for detailed brain dimensions, and diffusion tensor imaging (DTI) for nerve fiber tracks in the fetal period. A novel computational program will be compiled to detect features specifically as function of alcohol exposure. The association and dissociation of facial and brain dysmorphology as a function of dose and timing of alcohol exposure will be analyzed to better inform the diagnosis of FAS/ FASD. These studies will be a collaboration sharing resources and methods and will be performed across both Basic and Clinical Science components in consortium effort. To date there is no cure for FAS/FASD, which is a life long ordeal from the birth. Experimental tests, using the above model and setting, of trophic peptides which have been known to prevent neurodegeneration in trials for Alzheimer Disease and protect cell death in embryonic stage, have been partially tested in the embryonic period to show protection against the alcohol-induced retardation. The new studies will test whether the trophic peptides can prevent alcohol-induced brain and facial dysmorphology as well as behavioral impairment known to occur in FAS.
StatusFinished
Effective start/end date9/30/077/31/12

Funding

  • National Institutes of Health: $240,069.00
  • National Institutes of Health: $242,494.00
  • National Institutes of Health: $237,808.00
  • National Institutes of Health: $235,382.00
  • National Institutes of Health: $224,838.00

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Fetal Alcohol Spectrum Disorders
Alcohols
Brain
Therapeutics
Parturition
Facial Bones
Pregnancy
Western World
Peptides
Diffusion Tensor Imaging
Diagnostic Errors
Nerve Fibers
Neuroimaging
Intellectual Disability
Population
Alzheimer Disease
Cell Death
Tomography

ASJC

  • Medicine(all)