Grantee Research Project Results

Disruption of Ontogenic Development of Cognitive and Sensory Motor Skills

EPA Grant Number: R829391C003
Subproject: this is subproject number 003 , 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: Health Effects Institute (2005 — 2010)
Center Director: Greenbaum, Daniel S.
Title: Disruption of Ontogenic Development of Cognitive and Sensory Motor Skills
Investigators: Wagner, George
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:

Behavioral manifestations of developmental disorders may be characterized as “retardation” (a behavior fails to develop during a critical period), “regression” (a behavior develops at the right time but then is lost or exhibits a stunted rate of progression), or “intrusion” (appearance of behaviors aberrant in form or frequency). The period when symptoms appear may represent a time when environmental toxicants have accumulated in the brain to critical levels or the deleterious effects of early exposure become manifest through perturbation of normal development of brain pathways. Furthermore, certain individuals may be more sensitive to toxicants because of a genetic (perhaps immune-related) predisposition. Within this framework, the hypothesis that toxicants are causally involved in developmental disorders lends itself well to testing. In this proposal, a new paradigm for the study of toxicant-induced developmental disorders incorporating systematic assessment of retardation, regression, and/or intrusions in male and female mice of three strains will be developed. This will include a characterization of the ontogeny of key behaviors under normal conditions: (1) mid-air righting reflex and balance beam performance; (2) water maze (hidden platform) and passive avoidance behavior; and (3) water maze (visible platform), active avoidance, and stereotypic and self-injurious behavior. These behaviors have been linked to cerebellum, hippocampus, and striatum, brain areas known to be involved in developmental disorders and are known to be targets of lead and methylmercury (MeHg). The behavioral ontogeny will be linked to neural circuitry and synapse formation and the disruptive effects of low- dose exposure to each toxicant on the development of each behavior will be assessed at three time points over full dose-response curves. Thus, the specific objectives of this research project are to: (1) characterize the normal development of these behaviors in these three strains of mice; (2) evaluate the effects of acute and chronic low- dose exposure to lead and MeHg on these behaviors in each strain at each of three time points; (3) correlate the normal development with maturation of neural circuitry and synaptogenesis and the magnitude of toxicant-induced disruption of neurobehavioral development to morphological, neural circuitry, and neurochemical measures; and (4) evaluate the outcome in the context of this new paradigm in the form of the following question: Did toxicant exposure result in retardation,regression and/or intrusions in the neurobehavioral development of male or female mice of these strains?

Publications and Presentations:

Publications have been submitted on this subproject: View all 21 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, neurodevelopmental toxicity, biological response, growth & development, motor development, developmental neurotoxicity, environmental health hazard, environmental toxicant, metals, children's environmental health

Progress and Final Reports:

Main Center Abstract and Reports:

R829391 Health Effects Institute (2005 — 2010)

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.