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

ABSTRACT 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.

Download full-text


Available from: Kent Pinkerton, Oct 17, 2014
7 Reads
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use, and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake.
    Frontiers in Psychiatry 06/2013; 4:41. DOI:10.3389/fpsyt.2013.00041
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological studies suggest that events occurring during fetal and early childhood development influence disease susceptibility. Similarly, molecular studies in mice have shown that in utero exposure to cardiovascular disease (CVD) risk factors such as environmental tobacco smoke (ETS) increased adult atherogenic susceptibility and mitochondrial damage; however, the molecular effects of similar exposures in primates are not yet known. To determine whether perinatal ETS exposure increased mitochondrial damage, dysfunction and oxidant stress in primates, archived tissues from the non-human primate model Macaca mulatta (M. mulatta) were utilized. M. mulatta were exposed to low levels of ETS (1 mg/m(3) total suspended particulates) from gestation (day 40) to early childhood (1 year), and aortic tissues were assessed for oxidized proteins (protein carbonyls), antioxidant activity (SOD), mitochondrial function (cytochrome oxidase), and mitochondrial damage (mitochondrial DNA damage). Results revealed that perinatal ETS exposure resulted in significantly increased oxidative stress, mitochondrial dysfunction and damage which were accompanied by significantly decreased mitochondrial antioxidant capacity and mitochondrial copy number in vascular tissue. Increased mitochondrial damage was also detected in buffy coat tissues in exposed M. mulatta. These studies suggest that perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in primates, potentially increasing adult disease susceptibility.
    Cardiovascular toxicology 09/2010; 10(3):216-26. DOI:10.1007/s12012-010-9085-8 · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tierexperimentelle und klinische Studien haben ergeben, dass eine Nikotinexposition während der Gehirnentwicklung – beginnend pränatal bis zur Adoleszenz – neben morphologischen Veränderungen zu einer persistierenden Beeinflussung neuronaler Transmissionssysteme führen kann. Nikotinabhängigkeit sowie das Aufmerksamkeitsdefizit-Hyperaktivitäts-Syndrom sind mit einem Nikotinkonsum der Mütter der Betroffenen während der Schwangerschaft assoziiert. Auch finden sich erste Hinweise darauf, dass Nikotinmissbrauch in der Jugend die Funktion des zerebralen Aufmerksamkeitsnetzwerkes und das Gedächtnis nachhaltig beeinträchtigen kann. Unklar ist hingegen bislang noch, welche Auswirkungen eine Nikotinexposition auf die Entstehung von psychiatrischen Erkrankungen hat. Die somatischen Konsequenzen des Zigarettenrauchens und die resultierenden gesundheitsökonomischen Probleme sind bekannt, die Auswirkungen einer während der Gehirnentwicklung stattfindenden Nikotinexposition werden derzeit noch unterschätzt. Es sollte mehr Aufklärung der Bevölkerung erfolgen, um Nikotinkonsum bereits während der Schwangerschaft sowie bei Kindern und Jugendlichen zu vermeiden. Nicotine exposure during prenatal to adolescent neurodevelopment causes morphologic changes in the CNS and persistent alterations of neurotransmission systems. Maternal smoking on the one hand and nicotine dependency and attention deficit hyperactivity disorder in the offspring on the other are significantly associated. There is even evidence that nicotine abuse during adolescence may result in deficits of the brain’s attentional network. In contrast, any effects of nicotine exposure on the development of various psychiatric diseases are still unclear. The somatic consequences of smoking and the resulting economic problems are already well known, but the effects of nicotine on neurodevelopment are still underestimated. More public awareness training and medical education are required to avoid nicotine abuse in pregnant women, children, and adolescents.
    Der Nervenarzt 01/2008; 79(1):7-16. DOI:10.1007/s00115-007-2392-z · 0.79 Impact Factor
Show more