Prenatal exposure to nicotine impairs nervous system development at a dose which does not affect viability or growth

Navarro, Hernán A.; Fj, Seidler; Schwartz, Rochelle D.; Baker, FE; Dobbins, S S; Slotkin, T A

doi:10.1016/0361-9230(89)90146-9

Cited by 163 publications

(79 citation statements)

References 29 publications

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“…Pumps were prepared with concentrations of nicotine bitartrate (Sigma Chemical, St. Louis, MO) designed to deliver 0.7 mg of nicotine free base daily, dissolved in bacteriostatic water (Abbott Diagnostics, Abbott Park, IL). The average initial weight of the dams was 300 g and the final weight averaged 370 g, so that the dose rate was 2.3 mg/kg/day initially, falling to 1.9 mg/kg/day at the end of the infusion period (Navarro et al, 1989). The incision was closed with wound clips and the animals were permitted to recover in their home cages.…”

Section: Methodsmentioning

confidence: 99%

Prenatal Nicotine Exposure Evokes Alterations of Cell Structure in Hippocampus and Somatosensory Cortex

Roy

Seidler²,

Slotkin³

2002

J Pharmacol Exp Ther

162

123

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Offspring of women who smoke during pregnancy show behavioral abnormalities, including increased incidence of attentional deficit, learning disabilities, and cognitive dysfunction. Animal models indicate that nicotine elicits changes in neural cell replication and differentiation, leading to deficits in synaptic neurochemistry and behavioral performance, many of which first emerge at adolescence. We evaluated cellular morphology and regional architecture in the juvenile and adolescent hippocampus and the somatosensory cortex in rats exposed to nicotine prenatally. Pregnant rats were given nicotine throughout gestation via minipump infusion of 2 mg/kg/day, a regimen that elicits nicotine plasma levels comparable with those found in smokers. On postnatal days 21 and 30, brains were perfusionfixed, coronal slices were taken between the anterior commissure and median eminence, and the morphology of the dorsal hippocampus and somatosensory cortex was characterized. In the hippocampal CA3 region and dentate gyrus, we found a substantial decrease in cell size, with corresponding decrements in cell layer thickness, and increments in cell packing density. Smaller, transient changes were seen in CA1. In layer 5 of the somatosensory cortex, although there was no significant decrement in the average cell size, there was a reduction in the proportion of medium-sized pyramidal neurons, and an increase in the proportion of smaller, nonpyramidal cells. All regions showed elevated numbers of glia. Taken together with previous work on neurochemical and functional defects, these data demonstrate that prenatal nicotine exposure compromises neuronal maturation, leading to long-lasting alterations in the structure of key brain regions involved in cognition, learning, and memory.

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Section: Methodsmentioning

confidence: 99%

Prenatal Nicotine Exposure Evokes Alterations of Cell Structure in Hippocampus and Somatosensory Cortex

Roy

Seidler²,

Slotkin³

2002

J Pharmacol Exp Ther

162

123

View full text Add to dashboard Cite

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“…In animal studies, prenatal exposure to nicotine affects neuronal development and upregulates nAChRs in the brain [102][103][104][105] . Prenatal exposure to nicotine impairs protective responses to hypoxia in an age-dependent manner in rat pups [106] .…”

Section: Effects Of Perinatal Nicotine Exposure On Neonatal Respiratomentioning

confidence: 99%

Central cholinergic regulation of respiration: nicotinic receptors

Shao

Feldman

2009

Acta Pharmacol Sin

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Nicotinic acetylcholine receptors (nAChRs) are expressed in brainstem and spinal cord regions involved in the control of breathing. These receptors mediate central cholinergic regulation of respiration and effects of the exogenous ligand nicotine on respiratory pattern. Activation of α4* nAChRs in the preBötzinger Complex (preBötC), an essential site for normal respiratory rhythm generation in mammals, modulates excitatory glutamatergic neurotransmission and depolarizes preBötC inspiratory neurons, leading to increases in respiratory frequency. nAChRs are also present in motor nuclei innervating respiratory muscles. Activation of post-and/or extra-synaptic α4* nAChRs on hypoglossal (XII) motoneurons depolarizes these neurons, potentiating tonic and respiratory-related rhythmic activity. As perinatal nicotine exposure may contribute to the pathogenesis of sudden infant death syndrome (SIDS), we discuss the effects of perinatal nicotine exposure on development of the cholinergic and other neurotransmitter systems involved in control of breathing. Advances in understanding of the mechanisms underlying central cholinergic/nicotinic modulation of respiration provide a pharmacological basis for exploiting nAChRs as therapeutic targets for neurological disorders related to neural control of breathing such as sleep apnea and SIDS.

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“…During pregnancy, cigarette smoking causes low birth weight (Butler & Goldstein 1973, Navarro et al 1989, DiFranza & Lew 1995, and epidemiological studies suggest that maternal smoking during pregnancy might be a risk factor for childhood obesity (Morley et al 1995, Vik et al 1996, Blake et al 2000, von Kries et al 2002, Toschke et al 2002, Bergmann et al 2003, Wideroe et al 2003, Goldani et al 2007; however, the mechanisms to explain the development of obesity are still unclear. Newman et al (1999) observed that rats exposed to nicotine (NIC), the main addictive compound of tobacco smoke, in utero, are heavier at 9 weeks old when compared with controls.…”

Section: Introductionmentioning

confidence: 99%

Short- and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile, and thyroid function of rat offspring

Oliveira

Moura²,

Santos-Silva³

et al. 2009

Journal of Endocrinology

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Epidemiological studies show a higher prevalence of obesity in children from smoking mothers and smoking may affect human thyroid function. To evaluate the mechanism of smoking as an imprinting factor for these dysfunctions, we evaluated the programing effects of maternal nicotine (NIC) exposure during lactation. Two days after birth, osmotic minipumps were implanted in lactating rats, divided into: NIC (6 mg/kg per day s.c.) for 14 days; Control -saline. All the significant data were P!0 . 05 or less. Body weight was increased from 165 days old onwards in NIC offspring. Both during exposure (at 15 days old) and in adulthood (180 days old), NIC group showed higher total fat (27 and 33%). In addition, NIC offspring presented increased visceral fat and total body protein. Lipid profile was not changed in adulthood. Leptinemia was higher at 15 and 180 days old (36 and 113%), with no changes in food intake. Concerning the thyroid status, the 15-days-old NIC offspring showed lower serum-free tri-iodothyronine (FT 3 ) and thyroxine (FT 4 ) with higher TSH. The 180-days-old NIC offspring exhibited lower TSH, FT 3 , and FT 4 ). In both periods, liver type 1 deiodinase was lower (26 and 55%). We evidenced that NIC imprints a neonatal thyroid dysfunction and programs for a higher adiposity, hyperleptinemia, and secondary hypothyroidism in adulthood. Our study identifies lactation as a critical period to NIC programing for obesity, with hypothyroidism being a possible contributing factor.

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Prenatal exposure to nicotine impairs nervous system development at a dose which does not affect viability or growth

Cited by 163 publications

References 29 publications

Prenatal Nicotine Exposure Evokes Alterations of Cell Structure in Hippocampus and Somatosensory Cortex

Prenatal Nicotine Exposure Evokes Alterations of Cell Structure in Hippocampus and Somatosensory Cortex

Central cholinergic regulation of respiration: nicotinic receptors

Short- and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile, and thyroid function of rat offspring

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