Maternal exposure to nicotine and chlorpyrifos, alone and in combination, leads to persistently elevated expression of glial fibrillary acidic protein in the cerebellum of the offspring in late puberty

Abdel-Rahman, Ali; Dechkovskaia, Anjelika; Mehta-Simmons, Heena; Sutton, Jazmine M.; Guan, Xiangrong; Khan, Waris; Abou‐Donia, Mohamed B.

doi:10.1007/s00204-004-0560-5

Cited by 20 publications

(14 citation statements)

References 55 publications

(49 reference statements)

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“…The ETS-induced difference in GFAP was statistically significant as a main effect and as a regional interactive effect in hippocampus and cerebellum. The adult GFAP results correlate with previous observations of increased GFAP expression consequent to prenatal nicotine exposure (Abdel-Rahman et al 2003, 2004) and an increase in cell density in the developing brain from ETS (Slotkin et al 2006). …”

Section: Discussionsupporting

confidence: 88%

“…Astrogliosis was also observed in the developing brain after prenatal nicotine exposure, with increased glial fibrillary acid protein (GFAP) levels in the cerebellum and hippocampus of offspring (Abdel-Rahman et al 2003). Importantly, GFAP levels remained elevated out to postnatal day 60, and deficiencies in basic sensory motor skills were observed (Abdel-Rahman et al 2004), a long-term, functional effect. Susceptibility to ETS may differ between the developing and mature mammalian brains, but these data raise the potential of an astrocytic response following adult ETS exposure.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Environmental Tobacco Smoke on Adult Rat Brain Biochemistry

et al. 2009

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Environmental tobacco smoke (ETS) has been linked to deleterious health effects, particularly pulmonary and cardiac disease; yet, the general public considers ETS benign to brain function in adults. In contrast, epidemiological data have suggested that ETS impacts the brain and potentially modulates neurodegenerative disease. The present study begins to examine yet unknown biochemical effects of ETS on the adult mammalian brain. In the developed animal model, adult male rats were exposed to ETS 3 h a day for 3 weeks. Biochemical data showed altered glial fibrillary acid protein levels as a main treatment effect of ETS, suggestive of reactive astrogliosis. Yet, markers of oxidative and cell stress were unaffected by ETS exposure in the brain regions examined. Increased proteolytic degradation of αII-spectrin by caspase-3 and the dephosphorylation of serine 116 on PEA-15 indicated greater apoptotic cell death modulated by the extrinsic pathway in the brains of ETS-exposed animals. Further, β-synuclein was upregulated by ETS, a neuroprotective protein previously reported to exhibit anti-apoptotic and anti-fibrillogenic properties. These findings demonstrate that ETS exposure alters the neuroproteome of the adult rat brain, and suggest modulation of inflammatory and cell death processes.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Effects of Environmental Tobacco Smoke on Adult Rat Brain Biochemistry

et al. 2009

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“…The current results for noradrenergic systems are consonant with earlier studies of these specific interactions directed toward cholinergic or serotonergic circuits (Levin et al 2014; Slotkin et al 2014, 2015b; Slotkin and Seidler 2015), and therefore reinforce the idea that prenatal drug exposures can enhance the overall sensitivity of the developing brain to neurotoxicants. Our findings also provide the necessary, underlying defects at the level of synaptic function that verify the significance of morphological damage as reported earlier (Abdel-Rahman et al 2004; Abou-Donia et al 2006); specifically, because functional deficits provide more sensitive endpoints than gross anatomical effects, we were able to detect augmented synaptic changes that explain synergism at the behavioral level, even when enhanced toxicity cannot be detected at the morphological level. Most importantly, beyond the known liabilities associated with maternal smoking during pregnancy or with preterm delivery, our findings indicate the likelihood of heightened vulnerability to neurotoxic chemicals encountered later in life.…”

Section: Discussionsupporting

confidence: 89%

“…The cerebellum may be a particularly sensitive target for chlorpyrifos, and prenatal exposure is associated with neurochemical and structural changes that are likely to contribute to sensorimotor deficits (Abdel-Rahman et al 2004; Abou-Donia et al 2006; Crumpton et al 2000; Dam et al 1999; Garcia et al 2002; Krishnan 1993). Because the cerebellum is sparse in cholinergic projections, this region provides a distinctive model for exploring contributory neurotoxic mechanisms other than cholinergic hyperstimulation resulting from cholinesterase inhibition (Slotkin 2004, 2005); these alternative mechanisms are the ones that most likely contribute to the structural and behavioral deficits seen in children with low environmental exposures (Rauh et al 2011, 2012).…”

Section: Introductionmentioning

confidence: 99%

Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption by chlorpyrifos

2015

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We examined whether nicotine or dexamethasone, common prenatal drug exposures, sensitize the developing brain to chlorpyrifos. We gave nicotine to pregnant rats throughout gestation at a dose (3 mg/kg/day) producing plasma levels typical of smokers; offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces minimally-detectable inhibition of brain cholinesterase activity. In a parallel study, we administered dexamethasone to pregnant rats on gestational days 17–19 at a standard therapeutic dose (0.2 mg/kg) used in the management of preterm labor, followed by postnatal chlorpyrifos. We evaluated cerebellar noradrenergic projections, a known target for each agent, and contrasted the effects with those in the cerebral cortex. Either drug augmented the effect of chlorpyrifos, evidenced by deficits in cerebellar β-adrenergic receptors; the receptor effects were not due to increased systemic toxicity or cholinesterase inhibition, nor to altered chlorpyrifos pharmacokinetics. Further, the deficits were not secondary adaptations to presynaptic hyperinnervation/hyperactivity, as there were significant deficits in presynaptic norepinephrine levels that would serve to augment the functional consequence of receptor deficits. The pretreatments also altered development of cerebrocortical noradrenergic circuits, but with a different overall pattern, reflecting the dissimilar developmental stages of the regions at the time of exposure. However, in each case the net effects represented a change in the developmental trajectory of noradrenergic circuits, rather than simply a continuation of an initial injury. Our results point to the ability of prenatal drug exposure to create a subpopulation with heightened vulnerability to environmental neurotoxicants.

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“…It has also been suggested that GFAP is a sensitive and early biomarker of neurotoxicity, its up-regulation preceding anatomically perceptible damages in the brain [14-16]. Predominantly, only studies investigating developmental or in utero exposure to CPF have estimated GFAP expression [17,18]. The effect of dermal application of CPF on GFAP expression in the hippocampus has not been reported.…”

Section: Introductionmentioning

confidence: 99%

The effect of consequent exposure of stress and dermal application of low doses of chlorpyrifos on the expression of glial fibrillary acidic protein in the hippocampus of adult mice

Lim

Tay

Nadarajah

et al. 2011

J Occup Med Toxicol

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BackgroundChlorpyrifos (CPF), a commonly used pesticide worldwide, has been reported to produce neurobehavioural changes. Dermal exposure to CPF is common in industries and agriculture. This study estimates changes in glial fibrillary acidic protein (GFAP) expression in hippocampal regions and correlates with histomorphometry of neurons and serum cholinesterase levels following dermal exposure to low doses of CPF with or without swim stress.MethodsMale albino mice were separated into control, stress control and four treatment groups (n = 6). CPF was applied dermally over the tails under occlusive bandage (6 hours/day) at doses of 1/10th (CPF 0.1) and 1/5th dermal LD50 (CPF 0.2) for seven days. Consequent treatment of swim stress followed by CPF was also applied. Serum cholinesterase levels were estimated using spectroflurometric methods. Paraffin sections of the left hippocampal regions were stained with 0.2% thionin followed by the counting of neuronal density. Right hippocampal sections were treated with Dako Envision GFAP antibodies.ResultsCPF application in 1/10th LD50 did not produce significant changes in serum cholinesterase levels and neuronal density, but increased GFAP expression significantly (p < 0.001). Swim stress with CPF 0.1 group did not show increase in astrocytic density compared to CPF 0.1 alone but decreased neuronal density.ConclusionsFindings suggest GFAP expression is upregulated with dermal exposure to low dose of CPF. Stress combined with sub-toxic dermal CPF exposure can produce neurotoxicity.

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Maternal exposure to nicotine and chlorpyrifos, alone and in combination, leads to persistently elevated expression of glial fibrillary acidic protein in the cerebellum of the offspring in late puberty

Cited by 20 publications

References 55 publications

Effects of Environmental Tobacco Smoke on Adult Rat Brain Biochemistry

Effects of Environmental Tobacco Smoke on Adult Rat Brain Biochemistry

Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption by chlorpyrifos

The effect of consequent exposure of stress and dermal application of low doses of chlorpyrifos on the expression of glial fibrillary acidic protein in the hippocampus of adult mice

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