Abstract:
:This is the first in a series of studies investigating the developmental stage-specific neurobehavioral effects of all-trans retinoic acid (RA) exposure. Because high doses of this compound are known to be lethal to the developing organism, we first conducted a dose-response study to identify RA doses that produce low enough levels of gestational/postnatal mortality to make a behavioral analysis possible in survivors. Secondarily, at doses found to produce sufficient survivors on PND 28, effects on body and regional brain weights were examined. Finally, at these doses, effects on somatic malformations were evaluated. Four separate exposure periods were analyzed: gestational days (GD) 8 through 10, 11 through 13, 14 through 16, or postnatal days (PND) 3 through 5. In the postnatal exposure period rat pups were injected (s.c.) with three consecutive daily doses of 0, 5, 10, or 20 mg/kg RA on PND 3 through 5. This postnatal exposure had no detectable effect on survival, body or brain weight. In contrast, there was a marked sensitivity to RA in the GD 11-13 group. Many pups from dams given 10 mg/kg RA PO on GD 11-13 were found dead in the cage on the day of birth, and all surviving pups died within 4 days of birth. Examination of milkbands revealed no evidence of effective suckling in these short-term survivors. The same 10 mg/kg dose at GD 8-10 or GD 14-16 produced much lower mortality and pups appeared to suckle normally. To produce adequate PND 28 survival in the GD 11-13 group, it was necessary to reduce dosage to 2.5 mg/kg daily. Even this lower exposure produced effects on PND 28 body and brain weight, significantly lowering weights of body (84% of control), whole brain (94%), and cerebellum (90%). Cerebellar weight was also depressed as percent of whole brain weight, suggesting an effect focused specifically on this region. RA at 10 or 12.5 mg/kg over GD 14-16 also reduced cerebellar weight (92% and 91% of control, respectively). Thus, exposure on GD 14-16 had effects similar to those seen at GD 11-13, but only at considerably higher doses. In contrast, exposure to RA on GD 8-10 did not affect whole body or brain weight, and of eight brain regions examined, only brain stem weight was reduced (91% of control). The GD 8-10 exposure also differed substantially from later exposures in that it was the only treatment to produce substantial malformations, including exencephaly, eye and skeletal defects. We conclude that gestational exposure to RA produces lethality and regional brain stunting that is dose and developmental stage specific, with a pronounced sensitive period on GD 11-13. In contrast, the GD 8-10 period is most sensitive for production of malformations, albeit at somewhat higher doses.
journal_name
Neurotoxicol Teratoljournal_title
Neurotoxicology and teratologyauthors
Holson RR,Gazzara RA,Ferguson SA,Ali SF,Laborde JB,Adams Jdoi
10.1016/s0892-0362(97)00039-1subject
Has Abstractpub_date
1997-09-01 00:00:00pages
335-46issue
5eissn
0892-0362issn
1872-9738pii
S0892-0362(97)00039-1journal_volume
19pub_type
杂志文章abstract::Rapid euthanasia of laboratory rodents without the use of anesthesia is a necessary research technique whenever there is the likelihood of anesthesia or stress interfering with the chemistry of the tissues under investigation. Decapitation has long been the procedure of choice under such circumstances. Recently, howev...
journal_title:Neurotoxicology and teratology
pub_type: 指南,杂志文章
doi:10.1016/0892-0362(92)90004-t
更新日期:1992-07-01 00:00:00
abstract::This prospective study investigated the impact of early exposure to lead on the maturation of children's postural balance. The effect of lead exposure on age-associated maturation of postural balance was investigated on 91 children from the Cincinnati Lead Study (CLS) with a 5-year geometric mean lead concentration in...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2006.02.003
更新日期:2006-05-01 00:00:00
abstract::Exposure to ethanol during development can lead to a constellation of congenital anomalies, resulting in prenatal and postnatal failure to thrive, central nervous system (CNS) deficits, and a number of patterning defects that lead to defects in the cardiovascular system, facial structures, and limbs. The cellular, bio...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2004.06.016
更新日期:2004-11-01 00:00:00
abstract::Neurobehavioral studies often employ test batteries and confront issues of multiple testing and comparability between batteries. We have organized our battery of 12 tests into areas of neurobehavioral function to reduce the number of reported results, provide greater statistical power, and improve interpretability of ...
journal_title:Neurotoxicology and teratology
pub_type: 临床试验,杂志文章
doi:10.1016/0892-0362(96)00026-8
更新日期:1996-07-01 00:00:00
abstract::Inhalation exposure of male and female Fischer 344 rats to sulfuryl fluoride [Vikane (Dow Chemical Company) gas fumigant] at 300 ppm for 6 hr/day, 5 days week, for 13 weeks caused diminished weight gain, dental fluorosis, a slight decrease in grooming, decreased flicker fusion threshold, slowing of flash, auditory and...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(88)90076-1
更新日期:1988-03-01 00:00:00
abstract::To determine whether there is an association between moderate alcohol consumption in the first trimester of pregnancy and increased risk of fetal malformations, we conducted a literature search using Medline (1966-present), PsycLit (1974-1995), and EMBASE (1988-1995). The following inclusion criteria were used to sele...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章,meta分析
doi:10.1016/s0892-0362(97)00073-1
更新日期:1998-01-01 00:00:00
abstract::The central and peripheral nervous system effects of acute and subchronic exposure to three organic phosphoro-acid esters (dimethoate, dichlorvos, parathion-methyl) were studied. CNS-dependent variables included mean EEG amplitude, mean frequency of the EEG, and the activity (power density) of six component frequency ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(88)90004-9
更新日期:1988-09-01 00:00:00
abstract::Rats were fed a liquid diet containing ethanol from days 6-19 of gestation. Controls were pair-fed the same diet with sucrose substituted for ethanol, or received ad lib chow and water. The activity of the offspring was observed at 10, 16, 22 or 28 days-of-age. Overall, offspring exposed to alcohol prenatally were hyp...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(88)90067-0
更新日期:1988-01-01 00:00:00
abstract:BACKGROUND:Exposures to hydrogen sulfide gas (H2S) have been inconclusively linked to a variety of negative cognitive outcomes. We investigated possible effects on cognitive function in an urban population with chronic, low-level exposure to H2S. METHODS:Participants were 1637 adults, aged 18-65 years from Rotorua cit...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2014.02.002
更新日期:2014-03-01 00:00:00
abstract::Sulfites, which are commonly used as preservatives, are continuously formed in the body during metabolism of sulfur-containing amino acids. Sulfite is oxidized to sulfate ion by sulfite oxidase (SOX, EC. 1.8.3.1). The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring ac...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2004.10.002
更新日期:2005-01-01 00:00:00
abstract::In the United States, the regulation and testing of chemicals that may impact on human health is mandated by a number of different laws and regulated by several government agencies. Toxicologic screening in laboratory animals has created a major database for predicting adverse health effects of drugs, food and cosmeti...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章,评审
doi:10.1016/0892-0362(87)90052-3
更新日期:1987-11-01 00:00:00
abstract::Uranium is a heavy metal known to induce toxicity in kidneys. It is also known to enter the central nervous system, thus inducing neurophysiological effects, after exposure to relatively high concentrations. The effect of chronic uranium exposure (40 mg l(-1) in drinking water, for 90 days) on electroencephalographic ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2005.07.005
更新日期:2005-11-01 00:00:00
abstract::The effects of repeated SC administration of soman on schedule-controlled performance and brain pathology were studied in the rat. Soman suppressed response rates in both components of a multiple fixed interval 50-sec fixed-ratio 25 (mult. FI 50-sec FR 25) schedule of reinforcement, although all animals revealed marke...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(90)90112-p
更新日期:1990-01-01 00:00:00
abstract::Previous studies have indicated that prenatal ethanol (EtOH) exposure alters developing catecholamine (CA) systems and acute sensitivity to the locomotor stimulant effects of EtOH. The purpose of this study was to examine whether prenatal EtOH exposure influences the effects of the direct dopamine (DA) agonist apomorp...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(94)00055-i
更新日期:1995-01-01 00:00:00
abstract::The incidence of Fetal Alcohol Syndrome is now estimated at 0.97 cases per 1,000 live births in the general obstetric population and 4.3% among "heavy" drinkers. The general incidence is more than 20 times higher in the United States (1.95 per 1,000) compared to Europe and other countries (0.08 per 1,000). Within the ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章,评审
doi:10.1016/0892-0362(95)00005-c
更新日期:1995-07-01 00:00:00
abstract::Caffeine, added to the drinking water of males used for impregnation and gestant BALB/c mice such that their daily caffeine intake was 60 mg/kg, modified the passive avoidance behavior of the offspring when tested as adults. Caffeine-treated and control mice of the F1 generation were then cross-mated. The F2 generatio...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(89)90007-x
更新日期:1989-07-01 00:00:00
abstract::The study aim was to determine whether low level exposure to organophosphate pesticides (OPs) causes neuropsychological or psychiatric impairment. Methodological weaknesses of earlier studies were addressed by: recruiting participants who had retired on ill health grounds; excluding participants with a history of acut...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2010.03.004
更新日期:2010-07-01 00:00:00
abstract::Experimental models and clinical data indicate that the incidence of motor and learning disorders may be increased in children of epileptic mothers taking phenytoin (PHT) during pregnancy. There is little data on the vulnerability of infants to PHT-induced long-term behavioral toxicity after gestational or early life ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2004.12.006
更新日期:2005-03-01 00:00:00
abstract::Methylphenidate (MPD) is a dopamine uptake inhibitor and the most commonly prescribed drug for the treatment of attention-deficit/hyperactivity disorder in children. Several studies have shown that such stimulants as cocaine and amphetamine that are administered during gestation and lactation may disrupt maternal beha...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2015.05.008
更新日期:2015-07-01 00:00:00
abstract:BACKGROUND:Epidemiological studies examining the effects of prenatal toxic heavy metals exposure on neonatal development at the population-based level are limited. OBJECTIVE:To explore prenatal exposure levels to toxic heavy metals and examine whether exposure is associated with neonatal development. METHODS:A strati...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2011.05.010
更新日期:2011-07-01 00:00:00
abstract::The reduction in growth resulting from lead (PB) exposure in weanling rats is consistent with a lowering of the biological set-point for food intake. In this study the effects of lead on the patterns of food intake were examined. For 10 days (from ages 26 to 36 days), female rats were provided with drinking water cont...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(94)90040-x
更新日期:1994-11-01 00:00:00
abstract::Pregnant Swiss mice were exposed to 0.3-1.5 Gy of gamma radiation on day 17 of gestation and allowed to deliver the offspring. When the F1 mice were 6 months old, they were subjected to a number of behavioral tests. Open-field and dark-bright arena tests were conducted to study locomotor and exploratory activities. Le...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(98)00039-7
更新日期:1999-03-01 00:00:00
abstract::Visuoperceptual performance was examined in 146 9- to 12-year old children for whom prenatal exposure to marihuana and cigarettes had been ascertained. The subjects, participants in an ongoing longitudinal study, were from a low-risk, predominantly middle class sample. The tasks ranged in complexity from those that re...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(99)00046-x
更新日期:2000-01-01 00:00:00
abstract::Ionizing radiation is a precise tool for altering formation of the developing cerebral cortex of the fetal rat. Whole body exposure of the pregnant rat on gestational day 13, 15 or 17 to 1.0 Gy of gamma radiation resulted in maximum thinning of the cortex on days 15 and 17. In the preweaning period, functional tests (...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(88)90040-2
更新日期:1988-07-01 00:00:00
abstract::Long-Evans rats with micrencephaly induced by prenatal exposure to methylazoxymethanol acetate and normal controls were trained in a two-choice box to discriminate between stimuli of different brightness (black vs. white) or pattern (horizontal vs. vertical alternating black-and-white stripes). Mild footshock was used...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(90)90060-p
更新日期:1990-07-01 00:00:00
abstract::To explore the effects of gestational cocaine exposure in a nonhuman primate model, pregnant rhesus monkeys were either treated (N = 10) with escalating doses of cocaine up to 7.5 mg/kg (IM), three times per day, 5 consecutive days per week, prior to conception and throughout gestation, or were not treated (N = 10) wi...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(96)00187-0
更新日期:1997-01-01 00:00:00
abstract::Computer competition analysis of 3H-DHA (3H-dihydroalprenolol, a nonselective beta-adrenergic radioligand) binding in the presence of unlabeled metoprolol (a beta 1-selective antagonist) indicates the existence of both beta 1- and beta 2-adrenergic receptor subtypes in the rat placenta and confirms previous reports th...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(91)90026-s
更新日期:1991-01-01 00:00:00
abstract::Zidovudine (AZT) is the main therapeutic agent against HIV vertical transmission and is routinely administered to seropositive pregnant women and their newborns. Toxicity after chronic administration as well as citogenetic effects following developmental AZT exposure has been reported. Furthermore, recent animal data ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2004.09.008
更新日期:2005-01-01 00:00:00
abstract::Subcutaneous injection of a sublethal dose of chlorpyrifos (CHLP), an organophosphate (OP) pesticide, causes long-term inhibition in cholinesterase activity (ChE) of brain, blood, and other tissues. Such prolonged inhibition in ChE should lead to marked behavioral and autonomic thermoregulatory patterns, especially in...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(94)90002-7
更新日期:1994-01-01 00:00:00
abstract::Cognitive performance was examined in 145 thirteen- to sixteen-year-old adolescents for whom prenatal exposure to marihuana and cigarettes had been ascertained. The subjects were from a low-risk, predominantly middle-class sample participating in an ongoing, longitudinal study. The assessment battery included tests of...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(03)00029-1
更新日期:2003-07-01 00:00:00