Children's Health Research Center: Environmental Factors in the Etiology of Autism

Recipient Organization
UNIV OF CALIFORNIA (VET-MED)
(N/A)
DAVIS,CA 95616

Performing Department
MOLECULAR BIOSCIENCES

Non Technical Summary
Autism is a neurodevelopmental disorder defined by deficiencies of social reciprocity and communication and by repetitive behavior. The major goal of this project is to establish a multidisciplinary Center that examines the influence of xenobiotics on the incidence and severity of regressive childhood autism.

Animal Health Component

50%

Research Effort Categories

Basic

50%

Applied

50%

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
311	3840	1020	20%
311	3840	1030	20%
311	3840	1040	20%
311	3840	1080	20%
311	3840	1160	10%
311	3840	1170	10%

Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3840 - Laboratory animals;

Field Of Science
1040 - Molecular biology; 1030 - Cellular biology; 1160 - Pathology; 1080 - Genetics; 1020 - Physiology; 1170 - Epidemiology;

Goals / Objectives
This project consists of an administrative core, three facility cores and three current research projects. Facility Core 1: Analytic Biomarkers - The two major goals of this core are to develop strategies to profile xenobiotics of concern to childhood neurodevelopment in biological fluids and provide support in metabolomics. Facility Core II - Cellular Biomarkers - The Core has begun analysis of serologic samples from autistic and matched control children. Facility Core III - Molecular Biomarkers - The principal objective of this core is to identify patterns of altered gene expression that form a significant association with autism in human populations or which are coupled to specific environmental factors in animal models. Research Project 1 - Environmental Epidemiology of Autism Research Project II - Animal Models of Autism Research Project III - Molecular and Cellular Mechanisms of Autism.

Project Methods
Facility Core I - The long-term approach is to establish a horizontally integrated database from the genome through the autistic phenotype to aid in developing and testing hypotheses regarding the disorder. This core provides established analytical support for xenobiotic and proteomic profiling and is currently developing tools to study the metaboloms. Facility Core II - During this period the focus has been on defining tissue-specific antibiotics found in sera of patients with autism using a variety of neuronal antigens by immunoblot. Using patient sera, immunohistochemical analyses of brain tissue from autistic patients and controls have also been initiated. Currently pilot studies are underway using specimens obtained from the MIND institute tissue bank in preparation for CHARGE samples. Facility Core III - During this period the core has established a microarray facility that utilizes Affymetric GeneChip technology. An essential component of the Core's current efforts are to develop methods of analysis for microarray data in an effort to both better define and reduce the errors associated with the interpretation of the microarray results.

Progress 11/01/01 to 10/31/06

Outputs
The EPA agency contributed towards the establishment of the Center for Children's Health Research for Environmental Factors in the Etiology of Autism. This is a collaborative project also sponsored by NIH. The Center consists of an Administrative Core and 3 projects including a CHARGE Study Unit for regional center chart abstraction and data collection. This year extensive neurobehavioral ethograms were established at UCD for testing the influence of genetic and environmental factors in non-human primates and mice. The first postnatal thimerosal exposure study was completed in mice and the first and second behavioral assessment of Homer 1 knockout mouse was completed. Nonomolar thimerosal is discovered to induce DNA strand breaks in murine dendritic cells.

Impacts
This project established a multidisciplinary Center to examine the influence of xenobiotics on the incidence and severity of regressive childhood autism.

Publications

No publications reported this period

Progress 01/01/02 to 12/31/02

Outputs
Research Project 1 - Significant progress has been made for initiating the largest epidemiologic study of the genetic and environmental causes of autism (The CHARGE Study). Project managers for UCD and UCLA as well as other key personnel have been hired (web programmer, psychometric analyst and project coordinator). Research Project II - Goal is to establish in vivo exposure models in mice and primates with which to study how relevant xenobiotics of concern to childhood autism influence the development of social behavior. A battery of tests have been established to assess social behavior in developing and mature mice. Research Project III - Work has begun on assessing the influence of these xenobiotics on the growth and development of glial-hippocampal neurons in culture. The long-term goal is to define common mechanisms in immune and neural cells responsible for developmental toxicity of these environmental agents.

Impacts
This project establishes a multidisciplinary Center that examines the influence of xenobiotics on the incidence and severity of regressive childhood autism.

Publications

No publications reported this period