Open access
Review Article
1 June 2000

Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.

Publication: Environmental Health Perspectives
Volume 108, Issue suppl 3
Pages 511 - 533


Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.

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Published In

Environmental Health Perspectives
Volume 108Issue suppl 3June 2000
Pages: 511 - 533
PubMed: 10852851


Published online: 1 June 2000



D Rice
National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, D.C., USA.
S Barone, Jr
National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, D.C., USA.

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