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Cell signaling as a target and underlying mechanism for neurobehavioral teratogenesis
Joseph Yanai1, Ori Vatury, Theodore A Slotkin
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Abstract:
A wide variety of drugs and chemicals elicit neurobehavioral teratogenesis. Surprisingly, however, despite the obvious differences among unrelated compounds, the behavioral outcomes often display striking similarities, such as cognitive and attentional deficits. Recent studies of drugs of abuse (heroin, nicotine, barbiturates) and environmental toxins (environmental tobacco smoke, pesticides, metals) suggest that, regardless of the originating mechanism for perturbation of brain development, disparate neuroteratogens converge downstream on common families of alterations, characterized by changes in the expression and/or activity of the cell-signaling molecules that are essential to neuronal differentiation and synaptic communication. Identification of these common targets may help in the design of pharmacologic interventions that, administered in adulthood, can reverse the impact of exposure to neurobehavioral teratogens.
Insights
Neurobehavioral teratogens, including drugs and environmental toxins, cause similar cognitive and attentional deficits by altering cell signaling pathways in the brain. Identifying these common targets may lead to adult interventions for developmental neurotoxicity.
Area of Science:
- Neuroscience
- Developmental Toxicology
- Pharmacology
Background:
- Many drugs and chemicals cause neurobehavioral teratogenesis, leading to developmental neurotoxicity.
- Despite diverse origins, these teratogens often result in similar behavioral deficits, such as cognitive and attentional impairments.
Purpose of the Study:
- To investigate the common downstream molecular alterations caused by various neurobehavioral teratogens.
- To identify potential therapeutic targets for reversing the effects of developmental neurotoxicity.
Main Methods:
- Review of recent studies on drugs of abuse and environmental toxins.
- Analysis of changes in cell-signaling molecules essential for neuronal differentiation and synaptic communication.
Main Results:
- Disparate neuroteratogens converge on common alterations in cell-signaling pathways.
- These alterations affect neuronal differentiation and synaptic communication, underlying behavioral deficits.
Conclusions:
- Common downstream molecular targets exist for various neurobehavioral teratogens.
- Understanding these targets may enable the development of adult pharmacologic interventions to mitigate developmental neurotoxicity.