Grantee Research Project Results

Adhesion and Repulsion Molecules in Developmental Neurotoxic Injury

EPA Grant Number: R829391C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R829391
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: New Jersey Research Center for Environmental Bioinformatics and Computational Toxicology
Center Director: Welsh, William J.
Title: Adhesion and Repulsion Molecules in Developmental Neurotoxic Injury
Investigators: Reuhl, Kenneth R.
Institution: University of Medicine and Dentistry of New Jersey
EPA Project Officer: Hahn, Intaek
Project Period: November 1, 2001 through October 31, 2006
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

Normal brain development depends on the appropriate temporal and spatial expression of neural adhesion and repulsion molecules, several families of membrane proteins that provide instructive and permissive guidance for neuronal and neuritic movement. We postulate that neurotoxic metals perturb brain development/morphogenesis by disrupting the regulated expression and function of critical morphoregulatory adhesion and repulsion molecules. We further postulate that defects in these critical molecules give rise to morphological, biochemical, and behavioral effects of relevance to the study of autism spectrum disorder.

The objective of this research project is to address four specific questions: (1) Does exposure to neurotoxic metals alter the expression of adhesion and repulsion molecules during critical stages of brain development and thereby compromise morphogenesis? (2) Do selective transcriptional, translational, or post-translational processes mediate metal-induced changes in adhesion and repulsion molecules? (3) What are the behavioral consequences of toxicant-disturbed adhesion and repulsion molecules? (4) Can the deleterious effects of toxic metals on morphoregulatory molecules be modified or ameliorated by intervention strategies?

The studies utilize complementary biochemical and behavioral assessment to characterize the effects of toxic metals on neural cell adhesion molecules (NCAM), L-1, and the Eph family of tyrosine kinase repulsion molecules.

Publications and Presentations:

Publications have been submitted on this subproject: View all 23 publications for this subproject | View all 122 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 9 journal articles for this subproject | View all 85 journal articles for this center

Supplemental Keywords:

children’s health, disease and cumulative effects, ecological risk assessment, environmental chemistry, health risk assessment, risk assessments, susceptibility/sensitive population/genetic susceptibility, toxicology, genetic susceptibility, assessment of exposure, assessment technology, autism, behavioral assessment, behavioral deficits, childhood learning, children, developmental disorders, developmental effects, environmental health hazard, environmental toxicant, exposure assessment, gene-environment interaction, neurodevelopmental, neurological development, neuropathological damage, neurotoxic, neurotoxicity, outreach and education, public health,, Health, RFA, Scientific Discipline, Health Risk Assessment, Children's Health, Biochemistry, brain development, neurodevelopmental toxicity, autism, biological response, growth & development, developmental neurotoxicity, environmental health hazard, environmental toxicant, metals

Progress and Final Reports:

Main Center Abstract and Reports:

R829391 New Jersey Research Center for Environmental Bioinformatics and Computational Toxicology

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R829391C001 Neurotoxicant Effects on Cell Cycle Regulation of Neurogenesis
R829391C002 Adhesion and Repulsion Molecules in Developmental Neurotoxic Injury
R829391C003 Disruption of Ontogenic Development of Cognitive and Sensory Motor Skills
R829391C004 Exposure Assessment and Intervention Project (EAIP)
R829391C005 Clinical Sciences Project

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.