Perinatal Environmental Tobacco Smoke Exposure in Rhesus Monkeys: Critical Periods and Regional Selectivity for Effects on Brain Cell Development and Lipid Peroxidation

Duke University, Durham, North Carolina, United States
Environmental Health Perspectives (Impact Factor: 7.98). 02/2006; 114(1):34-9. DOI: 10.1289/ehp.8286
Source: PubMed


Perinatal environmental tobacco smoke (ETS) exposure in humans elicits neurobehavioral deficits. We exposed rhesus monkeys to ETS during gestation and through 13 months postnatally, or postnatally only (6-13 months). At the conclusion of exposure, we examined cerebrocortical regions and the midbrain for cell damage markers and lipid peroxidation. For perinatal ETS, two archetypal patterns were seen in the various regions, one characterized by cell loss (reduced DNA concentration) and corresponding increases in cell size (increased protein/DNA ratio), and a second pattern suggesting replacement of larger neuronal cells with smaller and more numerous glia (increased DNA concentration, decreased protein/DNA ratio). The membrane/total protein ratio, a biomarker of neurite formation, also indicated potential damage to neuronal projections, accompanied by reactive sprouting. When ETS exposure was restricted to the postnatal period, the effects were similar in regional selectivity, direction, and magnitude. These patterns resemble the effects of prenatal nicotine exposure in rodent and primate models. Surprisingly, perinatal ETS exposure reduced the level of lipid peroxidation as assessed by the concentration of thiobarbituric acid reactive species, whereas postnatal ETS did not. The heart, a tissue that, like the brain, has high oxygen demand, displayed a similar but earlier decrease (2-3 months) in lipid peroxidation in the perinatal exposure model, whereas values were reduced at 13 months with the postnatal exposure paradigm. Our results provide a mechanistic connection between perinatal ETS exposure and neurobehavioral anomalies, reinforce the role of nicotine in these effects, and buttress the importance of restricting or eliminating ETS exposure in young children.

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Available from: Kent Pinkerton, Oct 17, 2014
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    • "Particularly, chronic exposure to sidestream smoke simulating environmental tobacco smoke has been recently shown to induce behavioral and neurobiological changes in laboratory animals. In primates, prenatal and postnatal environmental smoke exposure induces neuronal damage to the cortex and midbrain (Slotkin et al., 2006) and impaired memory (Golub et al., 2007). In rats, chronic exposure during postnatal days 8–23 leads to perturbed mitochondrial processes in the cerebellum that is associated with a heightened locomotor response in a novel environment (Fuller et al., 2012). "
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    • "Similarly, depletion of mtDNA copy numbers have been noted in tissues (heart and skeletal muscle) from adults on zidovudine (AZT) therapy, and from infant primates exposed to AZT in utero [27–29]. A previous study investigating genomic DNA levels in brain tissues from the same monkeys used in these studies reported regional variation of DNA content compared to controls[30]; while those studies did not specifically examine mtDNA levels, they are consistent with tissue variances in DNA content between M. mulatta exposed to perinatal ETS compared to controls. It is possible that components of ETS capable of inducing damage and/or covalent association with genomic DNA, or more specifically, the mtDNA would contribute to mtDNA depletion by blocking the mitochondrial-specific polymerase γ and/or causing damage to the template strand, thus interfering with its replication. "
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