Nicotine exposure during pregnancy is a factor which influences serotonin transporter density in the rat brain

Muneoka, Katsumasa; Ogawa, Tetsuo; Kamei, Kaeko; Mimura, Yuichi; Kato, Hitomi; Takigawa, Morikuni

doi:10.1016/s0014-2999(00)00925-0

Cited by 53 publications

(25 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, in addition to the above-described findings, our results indicate a significant association among hypoplasia of the raphé nuclei, L/L or S/L genotypes, and maternal smoking in pregnancy. The effects of nicotine prenatal exposure on serotonin transporter expression have been examined till now only by Muneoka et al (36,37) in rat brain. These authors showed significant differences in 5-HT turnover in the midbrain and pons-medulla between rats treated with nicotine injections compared with controls.…”

Section: Discussionmentioning

confidence: 99%

Sudden Infant Death Syndrome and Sudden Intrauterine Unexplained Death: Correlation Between Hypoplasia of Raphé Nuclei and Serotonin Transporter Gene Promoter Polymorphism

et al. 2009

View full text Add to dashboard Cite

This study, besides to delineate the cytoarchitecture and the localization in the brainstem of the human raphé nuclei, aims to evaluate the correlation between neuropathological raphé defects and serotonin transporter gene (5-HTT) promoter region polymorphisms in a cohort of 28 SIDS victims, 12 sudden intrauterine unexplained deaths (SIUD), and 17 controls. Hypoplasia of one or more nuclei of both the rostral and caudal raphé groups was found in 57% of SIDS, in 67% of SIUD, and only in 12% of controls. Furthermore, a significant correlation among 5-HTT Long (L) allele, hypoplasia of the raphé nuclei, and maternal smoking in pregnancy was observed in sudden fetal and infant deaths. The presence of the L allele represents a predisposing factor for sudden fetal and infant death in association with morphologic developmental defects of the raphé nuclei and prenatal smoke exposure. A further consideration of the authors is that SIUD should not be regarded as a separate entity from SIDS, given the potentially shared neuropathological and genetic bases. additionally described an increase in number and density of serotonin cell bodies in the raphé, particularly in the raphé obscurus nucleus, in SIDS victims.The above-described neuropathological studies served as the impetus for investigation of genes regulating the synthesis, storage, membrane uptake, and metabolism of 5-HT, as well as related receptors in SIDS cohorts (4 -15). Key positive findings include the promoter region and intron 2 of the serotonin transporter gene (5-HTT) Long (L) allele, the L/L genotype, and the haplotype including the L alleles of both polymorphisms, and low frequency but apparent genetic variants in the FEV gene (11) and the PHOX2B gene (12). These results likely have a role in serotonin network dysfunction, resulting in a failure of autonomic and respiratory responses to hypoxia and/or hypercapnia, potentially resulting in risk for sudden death.Although the association of the promoter polymorphism L allele of the 5-HTT with SIDS has been widely documented, correlation with brainstem neuropathology and identification of all nuclei of the raphé complex in histopathologic studies in SIDS is limited. Further, the medullary serotonergic network in fetal life has not yet been described. Therefore, we aim to 1) clearly delineate the histology of the human raphé system in a cohort of SIDS victims and sudden intrauterine unexplained death (SIUD) cases; 2) determine the 5-HTT promoter region polymorphism in the same cohort of SIDS and SIUD; and 3) clarify the relationship of the 5-HTT L allele to cytoarchitectural alterations of the raphé complex in both the SIDS and SIUDs. Because maternal smoking is consistently identified as a risk factor for SIDS (16,17), the possible influence of maternal smoking in the serotonergic development will also be examined. MATERIALS AND METHODSStudy Subjects. The study included three groups of Caucasian infants: a SIDS cohort, a SIUD cohort, and a control group.SIDS and SIUD victims. The SIDS cases included ...

show abstract

Section: Discussionmentioning

confidence: 99%

Sudden Infant Death Syndrome and Sudden Intrauterine Unexplained Death: Correlation Between Hypoplasia of Raphé Nuclei and Serotonin Transporter Gene Promoter Polymorphism

et al. 2009

View full text Add to dashboard Cite

show abstract

“…However, animal studies have shown that prenatal administration of nicotine results in dopaminergic alterations in the neocortex and is a factor in serotonin transporter density in the rat brain (Muneoka et al, 1999(Muneoka et al, , 2001. Toschke et al (2002) have suggested that such changes might alter impulse control in offspring, leading to increased BMI.…”

Section: Discussionmentioning

confidence: 99%

Offspring from families at high risk for alcohol dependence: Increased body mass index in association with prenatal exposure to cigarettes but not alcohol

Hill¹,

Shen²,

Wellman³

et al. 2005

Psychiatry Research

View full text Add to dashboard Cite

The prevalence of overweight and obese children is increasing, a tendency that can be expected to increase the risk of adverse outcomes in adulthood. The aim of this study was to determine if prenatal exposure to alcohol, cigarettes, and street drugs would be associated with differences in body mass index (BMI) in childhood and adolescence in offspring from families at high and low genetic risk for developing alcohol dependence. Annual follow-up of offspring (N =288) provided 1200 height and weight assessments for analysis. Maternal substance use data were available for 235 offspring from families stratified for familial/genetic risk for alcohol dependence (high or low risk), providing the opportunity to assess prenatal exposure and familial/genetic risk in relation to BMI in the offspring. When data were grouped by the presence or absence of any prenatal cigarette exposure, a significant difference in offspring BMI was seen for 8-to 11-year-olds. Significant group differences were also seen at ages 12-15 and 16-18 years. A dose-response relationship between cigarette use by the mother and offspring BMI was also seen. With the strong tendency for individuals who are overweight in childhood and adolescence to become overweight adults, prenatal exposure to nicotine may be a harbinger of increased risk for numerous adultonset, weight-related health problems.

show abstract

“…We utilized established treatment regimens that deliver nicotine continuously throughout pregnancy or adolescence, achieving plasma nicotine concentrations comparable to that in smokers (Slikker et al, 2005;Slotkin, 1992Slotkin, , 1998Slotkin, , 2002Slotkin, , 2004. Our evaluations made use of families of biomarkers that typify cell number and size, acetylcholine (ACh) and serotonin (5HT) synaptic function and transsynaptic cell signaling, as established in earlier work with prenatal or adolescent nicotine exposure (Abreu-Villaça et al, 2003c, 2004bMuneoka et al, 2001;Navarro et al, 1989;Slotkin et al, 1987;Trauth et al, 2000a, b;Xu et al, 2001Xu et al, , 2002Zahalka et al, 1992;Zhu et al, 2000). First, we assessed the impact on neural cell number and size by measurements of DNA and cell protein fractions.…”

Section: Introductionmentioning

confidence: 99%

Permanent, Sex-Selective Effects of Prenatal or Adolescent Nicotine Exposure, Separately or Sequentially, in Rat Brain Regions: Indices of Cholinergic and Serotonergic Synaptic Function, Cell Signaling, and Neural Cell Number and Size at 6 Months of Age

Slotkin

MacKillop

Rudder

et al. 2006

Neuropsychopharmacol

146

116

View full text Add to dashboard Cite

Nicotine is a neuroteratogen that disrupts neurodevelopment and synaptic function, with vulnerability extending into adolescence. We assessed the permanence of effects in rats on indices of neural cell number and size, and on acetylcholine and serotonin (5HT) systems, conducting assessments at 6 months of age, after prenatal nicotine exposure, adolescent exposure, or sequential exposure in both periods. For prenatal nicotine, indices of cell number and size showed few abnormalities by 6 months, but there were persistent deficits in cerebrocortical choline acetyltransferase activity and hemicholinium-3 binding to the presynaptic choline transporter, a pattern consistent with cholinergic hypoactivity; these effects were more prominent in males than females. The expression of 5HT receptors also showed permanent effects in males, with suppression of the 5HT 1A subtype and upregulation of 5HT 2 receptors. In addition, cell signaling through adenylyl cyclase showed heterologous uncoupling of neurotransmitter responses. Nicotine exposure in adolescence produced lasting effects that were similar to those of prenatal nicotine. However, when animals were exposed to prenatal nicotine and received nicotine subsequently in adolescence, the adverse effects then extended to females, whereas the net effect in males was similar to that of prenatal nicotine by itself. Our results indicate that prenatal or adolescent nicotine exposure evoke permanent changes in synaptic function that transcend the recovery of less-sensitive indices of structural damage; further, prenatal exposure sensitizes females to the subsequent adverse effects of adolescent nicotine, thus creating a population that may be especially vulnerable to the lasting behavioral consequences of nicotine intake in adolescence.

show abstract

Nicotine exposure during pregnancy is a factor which influences serotonin transporter density in the rat brain

Cited by 53 publications

References 21 publications

Sudden Infant Death Syndrome and Sudden Intrauterine Unexplained Death: Correlation Between Hypoplasia of Raphé Nuclei and Serotonin Transporter Gene Promoter Polymorphism

Sudden Infant Death Syndrome and Sudden Intrauterine Unexplained Death: Correlation Between Hypoplasia of Raphé Nuclei and Serotonin Transporter Gene Promoter Polymorphism

Offspring from families at high risk for alcohol dependence: Increased body mass index in association with prenatal exposure to cigarettes but not alcohol

Permanent, Sex-Selective Effects of Prenatal or Adolescent Nicotine Exposure, Separately or Sequentially, in Rat Brain Regions: Indices of Cholinergic and Serotonergic Synaptic Function, Cell Signaling, and Neural Cell Number and Size at 6 Months of Age

Contact Info

Product

Resources

About