DEVELOPMENTAL CONSIDERATIONS OF NEUROTOXIC EXPOSURES
Section snippets
CONCEPTS REGARDING BRAIN DEVELOPMENT AND BEHAVIOR
The purpose of this article is to give the reader a perspective regarding developmental considerations in neurotoxicology. Many comprehensive papers have reviewed the extensive number of testing instruments available to assess neurobehavioral and cognitive development in neonates, infants, and children including measures emphasizing pediatric neurologic, developmental psychologic, and cognitive/information processing functions.3, 29, 56 The goal of this article is not to list or evaluate such
General Methodological Considerations
One goal central to developmental neurotoxicology is to establish a link between a potential neurotoxic exposure and specific adverse neurobehavioral outcomes in exposed children. To establish this link requires the synthesis of multiple sources of information. First, evidence regarding the potential neurotoxicity of the agent must be reviewed in both animal models and epidemiologic literature, with particular attention to the specific substance at a particular dose and duration within a
Mechanisms of Nicotine-Induced Brain Maldevelopment.
Nicotine is easily transferred across the placental membranes, and fetal cord serum concentrations have been found at levels at or above those in maternal serum.65 The developmental neurotoxicity of nicotine has been attributed to its action as a direct agonist at nicotinic cholinergic receptors, resulting in primary alterations in cholinergic neurotransmission and secondary changes in catecholamine, i.e., norepinephrine and dopamine and glutamate neurotransmission.93 Alterations in these
Lead
The definition of lead poisoning has fluctuated over time. Before 1970, it was generally assumed that blood lead levels in excess of 60 μg/dL were required to produce toxic effects in children.118 In 1986 the World Health Organization revised the acceptable limit to 20 μg/dL, and more recently, the Centers for Disease Control guidelines13 have revised the intervention level downward to 10 μg/dL. Approximately 17.2% of children in the United States ages 6 months to 5 years are believed to have
SYNTHESIS AND CONCLUSIONS
Evaluating the effects of neurotoxic agents on developing organisms can be complicated by many factors. It is important to consider the species being studied, the dose and route of neurotoxin exposure, the developmental stage of exposure, and the interactive effect of that neurotoxin with other environmental variables. Animal models afford the unique opportunity for focusing on the mechanisms of action and identifying particular brain structures and neurochemical systems affected by particular
References (127)
- et al.
Prenatal nicotine exposure modifies behavior of mice through early development
Pharmacol Biochem Behav
(1998) - et al.
Selective approaches to basic neurobehavioral testing of children in environmental health studies
Neurotoxicol Teratol
(1996) - et al.
Mental development of 2-year-old children exposed to alcohol in utero
J Pediatr
(1992) - et al.
Methylmercury developmental neurotoxicity: A comparison of effects in humans and animals
Neurotoxicol Teratol
(1990) Environmental contaminants in the food chain
Am J Clin Nutrition
(1995)- et al.
Dose-response analysis of infants prenatally exposed to methyl mercury: An application of a single compartment model to single-strand hair analysis
Environ Res
(1989) - et al.
Fear-potentiated startle: A neural and pharmacological analysis
Behavioral Brain Res
(1993) - et al.
The effects of prenatal tobacco and marijuana use on offspring growth from birth through 3 years of age
Neurotoxicol Teratol
(1992) - et al.
- et al.
Structural and functional effects of prenatal cocaine exposure in adult rat brain
Dev Brain Res
(1990)
Prenatal alcohol exposure: Comparability of effects in humans and animal models
Neurotoxicol Teratol
Effects of neonatal exposure to nicotine on electrophysiological parameters in adult rats
Pharmacol Biochem Behav
Exposure to nicotine during a defined period in neonatal life induces permanent changes in brain nicotinic receptions and in behaviour of adult mice
Brain Res
A follow-up study of attentional behavior in 6-year-old children exposed prenatally to marijuana, cigarettes, and alcohol
Neurotoxicol Teratol
Growth from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana
Neurotoxicol Teratol
Analysis of receptor-stimulated and basal guanine nucleotide binding to membrane G proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
Anal Biochem
Cocaine-induced disturbances of corticogenesis in the developing murine brain
Neurosci Lett
A neuropsychological study of children with elevated dentine lead level: Assessment of the effect of lead in different socioeconomic groups
Neurotoxicol Teratol
Epidemiological and clinical features of Minamata disease
Environ Res
Pattern of malformation in offspring of chronic alcoholic mothers
Lancet
Recall bias in disease status associated with perceived exposure to hazardous substances
Ann Epidemiol
Neurobehavioral test strategies for environmental exposures in pediatric populations
Neurotoxicol Teratol
Presynaptic glutamatergic function in dentate gyrus in vivo is diminished by chronic exposure to inorganic lead
Brain Res
Prenatal substance exposure: Effect on attention and impulsivity of 6-year-olds
Neurotoxic Teratol
Lead activates protein kinase C in immature rat brain microvessels
Toxicol Appl Pharmacol
Prenatal cocaine administration stimulates fetal brain tyrosine hydroxylase activity
Brain Res
Delayed evoked potentials in children exposed to methylmercury from seafood
Neurotoxicol Teratol
Operant test battery performance in children: Correlation with IQ
Neurotoxicol Teratol
Apparent central neurotransmitter receptor changes induced by low-level lead exposure during different developmental phases in the rat
Toxicol Appl Pharmacol
Prenatal cocaine increases striatal serotonin innervation without altering the patch/matrix organization of intrinsic cell types
Dev Brain Res
Neurobehavioral assessment during the early postnatal period
Neurotoxicol Teratol
Postnatal changes in [3H]mazindol-labelled dopamine uptake sites in the rat striatum following prenatal cocaine exposure
Brain Res
Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity. Work Group I report: Comparability of measures of developmental neurotoxicity in humans and laboratory animals
Neurotoxicol Teratol
Increased tyrosine hydroxylase immunoreactivity in the rat cortex following prenatal cocaine exposure
Dev Brain Res
Methylmercury in astrocytes: What possible significance
Neurotoxicol
Use of questionnaires in occupational studies of pregnancy outcomes: Validation of questionnaire reported miscarriage, malformation, and birth weight
Int J Epidemiol
Pediatric Neuropsychology in the Medical Setting
Longitudinal analysis of prenatal and postnatal lead exposure in early cognitive development
N Engl J Med
Antecedents and correlates of improved cognitive performance in children exposed in utero to low levels of lead
Environ Health Perspect
Cord blood alpha-fetaprotein concentration in term newborns of smoking mothers
Eur J Pediatr
Smoking in pregnancy and subsequent child development
Br Med J
Preventing Lead Poisoning in Young Children: A Statement by the Centers for Disease Control
The biological monitoring of mercury in the Seychelles study
Neurotoxicology
Molecular mechanisms of ethanol intoxication, tolerance, and physical dependence
Cocaine/poly-drug use in pregnancy: Two year follow-up
Pediatrics
Prenatal exposure to cocaine and other drugs: Outcome at four to six years
Ann New York Acad Sci
Neurological correlates of fetal cocaine exposure: Transient hypertonia of infancy and early childhood
Pediatrics
Neurological correlates of fetal cocaine exposure
Ann New York Academy of Sci
Abnormal neuronal migration, deranged cortical organization, and diffuse white matter astrocytosis of human fetal brain: A major effect of methylmercury poisoning in utero
J Neuropathol Exp Neurol
Relationships between Pb-induced changes in neurotransmitter system function and behavioral toxicity
Neurotoxicology
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2010, Advances in Child Development and BehaviorCitation Excerpt :These stressors can also affect brain development by altering the metabolism and thus, the function of the cells. The psychopathology associated with these factors includes mental retardation, hyperkinetic disorders, and significant emotional disturbance (for review, see Trask & Kosofsky, 2000). Although these factors have their most profound effect early in gestation, the older fetus is still vulnerable to maternally-transmitted infections and toxins.
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Address reprint requests to Barry Kosofsky, MD, PhD, Laboratory of Molecular and, Developmental Neuroscience, Massachusetts General Hospital—East, 149 13th Street, Charlestown, MA 02129