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A model of the development of the brain as a construct of the thyroid system
1Wildlife and Contaminants Program, World Wildlife Fund, 1250 24th Street NW, Washington, DC 20037-9736, USA. kembra.howdeshell@wwfus.org
Abstract:
Thyroid hormone is essential for normal brain development. However, little is known about the molecular and cellular mechanisms that mediate thyroid hormone action on the developing brain or the developmental events selectively affected. Consequently, although a large number of environmental chemicals interfere with the thyroid system, there are few neurodevelopmental end points to recruit for toxicological studies. Therefore, my goal here is to review what is known about the relative timing of normal brain construction and thyroid system development, with special focus on the period of in utero development in humans and the comparable developmental period in laboratory rats. These data are presented as a timeline to aid in the identification of thyroid-sensitive end points in brain development and to highlight important data gaps. I discuss the known influence of certain synthetic chemicals on the thyroid system and include a brief review of the effects of developmental exposure to chemicals on thyroid system function. The relationship between the thyroid hormone and retinoic acid systems, as well as the thyroid hormone sensitivity of the developing cochlea, is also discussed.
Insights
Thyroid hormone is crucial for brain development. This review outlines key developmental timings and identifies thyroid-sensitive neurodevelopmental endpoints for toxicological studies.
Area of Science:
- Neuroscience
- Endocrinology
- Developmental Biology
Background:
- Thyroid hormone is vital for normal brain development.
- Mechanisms of thyroid hormone action and affected developmental events are poorly understood.
- Environmental chemicals can disrupt the thyroid system, but specific neurodevelopmental endpoints for study are limited.
Purpose of the Study:
- To review the timing of brain and thyroid system development, focusing on in utero periods in humans and rats.
- To identify thyroid-sensitive neurodevelopmental endpoints for toxicological assessment.
- To highlight data gaps in understanding thyroid hormone's role in brain development.
Main Methods:
- Comparative timeline analysis of human and rat brain and thyroid system development.
- Review of existing literature on thyroid hormone action in the brain.
- Discussion of chemical exposures affecting the thyroid system.
Main Results:
- A timeline is presented to aid in identifying critical windows of thyroid hormone sensitivity during brain development.
- Specific neurodevelopmental endpoints susceptible to thyroid disruption are highlighted.
- Data gaps concerning thyroid hormone's role and chemical impacts are identified.
Conclusions:
- Establishing a developmental timeline is crucial for identifying neurodevelopmental endpoints affected by thyroid disruption.
- Further research is needed to understand molecular mechanisms and chemical impacts on thyroid hormone-mediated brain development.
- This work provides a framework for future toxicological studies on environmental chemical effects on neurodevelopment.