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Accession Number:
AD1013427
Title:
The Effects of Low Level Prenatal Carbon Monoxide on Neocortical Development
Descriptive Note:
Technical Report
Corporate Author:
Uniformed Services University Of The Health Sciences Bethesda United States
Report Date:
2010-06-02
Pagination or Media Count:
143.0
Abstract:
The prevalence of maternal smoking remains surprisingly high, ranging from 10-50 of pregnant women across different countries and socioeconomic groups. This is associated with several adverse neurological outcomes including increased risk for Sudden Infant Dealth Syndrome, attention deficit disorder, and autism. Prenatal exposure to carbon monoxide CO, a major toxic constituent of cigarette smoke, disrupts development of diverse brain structures and associates with similar neurological disorders. While the global effects of CO on the developing brain have been studied, the specific effects of CO on neocortical development and neuronal migration have not. In the first set of experiments we determined if CO exposure resulted in structural changes of the neocortex. Pregnant mice CD1 were exposed to different concentrations of CO approximating levels found in smokers 0 or 150 ppm from embryonic day 7 E7 until birth. Bromodeoxyuridine BrdU was injected on either E12 or E16 to map the distribution of neocortical cells born on that date. Neocortical cells born early during corticogenesis E12 were abnormally distributed toward the upper layers while later born neocortical cells E16 were abnormally distributed toward the middle layers of the neocortex in adult mice exposed to CO in utero. A greaterpercentage of BrdU cells colocalized with GAD 6567 in treated vs controls,suggesting impairment of interneuron migration. Futhermore, the displaced cells did not co-localize with markers for projection neurons including MAP2 and CAMK-II. Treated mice also had altered distributions of GABAergic interneurons throughout the neocortex with a decreased density in the upper layers and an increased proportion of cells in central layers, suggesting they did not reach their intended target.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
