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Neurotoxicology. 2006 Dec;27(6):1032-42. Epub 2006 Jun 7.

Gestational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure effects on sensory cortex function.

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Department of Biomedical Sciences, Division of Neurobiology and Neurotoxicology, Center for Molecular and Behavioral Neuroscience, Meharry Medical College, Nashville, TN 37208, USA.


Gestational exposure to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poses a significant threat to normal growth and differentiation of the developing brain. To characterize the impact of gestational TCDD exposure on subsequent cortical function, pregnant Long Evans rats were exposed to a single acute dose (100 or 700ng/kg b.w. via gavage) on gestational day 15. This dosing regimen had no significant effect on birth index. After the TCDD-exposed animals were born and reached maturity, neural activity was recorded under urethane anesthesia from neurons in primary somatic sensory cortex. Spontaneous activity was reduced by approximately 50% in barrel cortex compared to corn oil vehicle controls. The magnitude of neuronal response to sensory (whisker) stimuli also was significantly reduced, and responses did not achieve control levels at any stimulus intensity. The greatest deficit was in the short latency component of the cortical responses. These decrements in cortical responsiveness were present in young F1 generation TCDD-exposed animals and persisted for up to 180 days. Because glutamate receptors are crucial to the evoked responses and show developmental regulation, selected iontotropic glutamate receptor subunits (NMDA NR2A+NR2B and GluR1) were profiled for RNA levels in the cortex of F1 generation rats. The expression of NR2B (NMDA receptor) and GluR1 (AMPA receptor) subunits was significantly reduced in the TCDD-exposed F1 generation animals compared to vehicle controls. The results indicate that gestational TCDD exposure results in cortical deficits that are paralled by diminished expression of certain NMDA and AMPA receptor subunits at a time when synapses are being formed for the first time in cortex.

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