Neurobehavioural defects in adult mice neonatally exposed to nicotine: changes in nicotine-induced behaviour and maze learning performance

Ankarberg, Emma; Fredriksson, Anders; Eriksson, Per

doi:10.1016/s0166-4328(01)00207-8

Cited by 41 publications

(32 citation statements)

References 20 publications

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“…For example, nicotine per se as toxic chemical may affect the development of nAChRs in the fetal brain. It is known that nicotine from maternal side can easily pass the placental barrier and be rapidly absorbed into the fetal bloodstream (Ankarberg et al, 2001;Dempsey and Benowitz, 2001). Considering a high dose of nicotine was used in the present study, the substance in the fetal circulation may act directly on the brain nAChRs.…”

Section: Discussionmentioning

confidence: 97%

“…Nicotine as a principal psychoactive component in tobacco smoke can activate nicotinic acetylcholine receptors (nAChRs). Nicotine crosses the placenta, and maternal smoking causes accumulation of nicotine in fetal tissues (Ankarberg et al, 2001;Dempsey and Benowitz, 2001), resulting in fetal growth restriction and impaired brain development. Animal models have been used to study short-and long-term consequences of exposure to nicotine in an attempt to link nicotine to the observed adverse effects found in babies.…”

Section: Introductionmentioning

confidence: 99%

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The effect of prenatal nicotine on expression of nicotine receptor subunits in the fetal brain

Mao

Zhu

et al. 2008

NeuroToxicology

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Previous studies have suggested that prenatal exposure to nicotine is associated with abnormal development in fetuses, including fetal brain damage. The present study determined the effect of maternal administration of nicotine during different gestational periods on brain nicotine receptor subunits in fetal rats. Subcutaneous injections of nicotine in maternal rats from the early and middle gestation decreased fetal blood PO 2 , increased fetal blood PCO 2 and hemoglobin, and decreased fetal brain weight. The nicotinic acetylcholine receptor (nAChRs) mRNA abundance in the fetal brain was significantly changed by prenatal treatment with nicotine during pregnancy. Fetal α2, α4, α7, and β2 units were significantly increased in the brain by prenatal exposure to nicotine in rat fetuses. However, the expression of mRNA of fetal brain α3, α5, β3, and β4 units were not changed. The results showed that prenatal nicotine can change the development of both α and β subunits of nAChRs in the fetal brain at gene level in association with restriction of fetal brain growth and in utero hypoxia.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

The effect of prenatal nicotine on expression of nicotine receptor subunits in the fetal brain

Mao

Zhu

et al. 2008

NeuroToxicology

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“…Although cigarettes deliver hundreds of different compounds, including tars, carbon monoxide and cyanide, nicotine is the major psychoactive ingredient in tobacco. It is rapidly absorbed into the blood stream and reaches the fetus at concentrations equal to or higher than those in the mother (Ankarberg et al, 2001;Dempsey and Benowitz, 2001). Therefore, studies have focused on the developmental effects of nicotine which is believed to be, at least in part, responsible for the adverse effects of tobacco smoking during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

“…Animal studies have tried to link prenatal nicotine exposure to cognitive deficits, but with limited success (Cutler et al, 1996;Ajarem and Ahmad, 1998;Ankarberg et al, 2001;AbdelRahman et al, 2005). Two late developing brain structures, the hippocampus and the cerebellum, are associated with cognitive functions.…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology in hippocampus and cerebellum

2007

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Nicotine, the major psychoactive ingredient in tobacco interacting with nicotinic acetylcholine receptors (nAChR), is believed to have neuroprotective and neurotoxic effects on the developing brain. Neurotoxicity has been attributed to activation of homomeric α7 nAChRs, neuroprotection to heteromeric α4β2 nAChRs. Thus, developmental nicotine could have opposite effects in different brain regions, depending on nAChR subtype expression. Here, we determined if chronic neonatal nicotine exposure (CNN), during a period of brain growth corresponding to the third human trimester, differentially regulates nAChR expression, cell death, and morphological properties in hippocampus and cerebellum, two structures maturing postnatally. Rat pups were orally treated with 6 mg/kg/day nicotine from postnatal day (P)1 to P7. On P8, expression for α4, α7 and β2 mRNA was determined by in situ hybridization; nAChR binding sites in by receptor autoradiography, dying neurons by TUNEL and Fluoro-Jade staining and morphological properties by analysis of Cresyl-Violet stained sections. In control cerebellum, strong expression of α4, β2 mRNA and heteromeric nAChRs labeled with [ 125 I]-Epibatidine were found in granule cells, and α7 mRNA and homomeric nAChRs labeled with [ 125 I]-αBungarotoxin in the external germinal layer. In control hippocampus, low expression of α4 mRNA and heteromeric nAChRs and high expression of α7 mRNA and homomeric nAChRs were detected. CNN increased heteromeric nAChR binding in hippocampus but not cerebellum and significantly decreased neuronal soma size and increased packing density in hippocampal principal cells but not in cerebellum. CNN did not increase the number of dying cells in any area, but significantly fewer TUNEL-labeled cells were found in CA3 strata oriens and radiatum and cerebellar granule layer. Thus, the hippocampus seems to be more sensitive than the cerebellum to CNN which could result from different nAChR subtype expression and might explain long-lasting altered cognitive functions correlated with gestational nicotine exposure due to changes in hippocampal cell morphology.

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“…Following neonatal exposure to nicotine, mice developed significant memory impairment; however, this did not appear until the age of 7 months (Ankarberg et al 2001). The mechanism behind this is unclear.…”

Section: Nicotine Enhancement Of Cognitionmentioning

confidence: 99%

Nicotinic acetylcholine receptors: from structure to brain function

Hogg

Raggenbass

Bertrand

Reviews of Physiology, Biochemistry and Pharmacology

458

370

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Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels and can be divided into two groups: muscle receptors, which are found at the skeletal neuromuscular junction where they mediate neuromuscular transmission, and neuronal receptors, which are found throughout the peripheral and central nervous system where they are involved in fast synaptic transmission. nAChRs are pentameric structures that are made up of combinations of individual subunits. Twelve neuronal nAChR subunits have been described, alpha2-alpha10 and beta2-beta4; these are differentially expressed throughout the nervous system and combine to form nAChRs with a wide range of physiological and pharmacological profiles. The nAChR has been proposed as a model of an allosteric protein in which effects arising from the binding of a ligand to a site on the protein can lead to changes in another part of the molecule. A great deal is known about the structure of the pentameric receptor. The extracellular domain contains binding sites for numerous ligands, which alter receptor behavior through allosteric mechanisms. Functional studies have revealed that nAChRs contribute to the control of resting membrane potential, modulation of synaptic transmission and mediation of fast excitatory transmission. To date, ten genes have been identified in the human genome coding for the nAChRs. nAChRs have been demonstrated to be involved in cognitive processes such as learning and memory and control of movement in normal subjects. Recent data from knockout animals has extended the understanding of nAChR function. Dysfunction of nAChR has been linked to a number of human diseases such as schizophrenia, Alzheimer's and Parkinson's diseases. nAChRs also play a significant role in nicotine addiction, which is a major public health concern. A genetically transmissible epilepsy, ADNFLE, has been associated with specific mutations in the gene coding for the alpha4 or beta2 subunits, which leads to altered receptor properties

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Neurobehavioural defects in adult mice neonatally exposed to nicotine: changes in nicotine-induced behaviour and maze learning performance

Cited by 41 publications

References 20 publications

The effect of prenatal nicotine on expression of nicotine receptor subunits in the fetal brain

The effect of prenatal nicotine on expression of nicotine receptor subunits in the fetal brain

Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology in hippocampus and cerebellum

Nicotinic acetylcholine receptors: from structure to brain function

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