In the adult nervous system, neurotransmitters mediate cellular communication within neuronal circuits. In developing tissues and primitive organisms, neurotransmitters subserve growth regulatory and morphogenetic functions. Accumulated evidence suggests that acetylcholine, (ACh), released from growing axons, regulates growth, differentiation, and plasticity of developing central nervous system neurons. In addition to intrinsic cholinergic neurons, the cerebral cortex and hippocampus receive extensive innervation from cholinergic neurons in the basal forebrain, beginning prenatally and continuing throughout the period of active growth and synaptogenesis. Acute exposure to ethanol in early gestation (which prevents formation of basal forebrain cholinergic neurons) or neonatal lesioning of basal forebrain cholinergic neurons, significantly compromises cortical development and produces persistent impairment of cognitive functions. Neonatal visual deprivation alters developmental expression of muscarinic acetylcholine receptors (mAChR) in visual cortex, whereas local infusion of mAChR antagonists impairs plasticity of visual cortical neurons. These findings raise the possibility that exposure to environmental neurotoxins that affect cholinergic systems may seriously compromise brain development and have long-lasting morphologic, neurochemical, and functional consequences. (+info)
The effect of the timing of ethanol exposure during early postnatal life on total number of Purkinje cells in rat cerebellum.
We have previously shown that exposing rats to a high dose of ethanol on postnatal d 5 can affect Purkinje cell numbers in the cerebellum whilst similar exposure on d 10 had no such effect. The question arose whether a longer period of ethanol exposure after d 10 could produce loss of Purkinje cells. We have examined this question by exposing young rats to a relatively high dose (approximately 420-430 mg/dl) of ethanol for 6 d periods between the ages of either 4 and 9 d or 10 and 15 d of age. Exposure was carried out by placing the rats in an ethanol vapour chamber for 3 h per day during the exposure period. Groups of ethanol-treated (ET), separation controls (SC) and mother-reared controls (MRC) were anaesthetised and killed when aged 30 d by perfusion with buffered 2.5% glutaraldehyde. Stereological methods were used to determine the numbers of Purkinje cells in the cerebellum of each rat. MRC, SC and rats treated with ethanol between 10-15 d of age each had, on average, about 254-258 thousand cerebellar Purkinje cells; the differences between these various groups were not statistically significant. However, the rats treated with ethanol vapour between 4-9 d of age had an average of only about 128000+/-20000 Purkinje cells per cerebellum. This value was significantly different from both the MRC and group-matched SC animals. It is concluded that the period between 4 and 9 d of age is an extremely vulnerable period during which the rat cerebellar Purkinje cells are particularly susceptible to the effects of a high dose of ethanol. However, a similar level and duration of ethanol exposure commencing after 10 d of age has no significant effect on Purkinje cell numbers. (+info)
Was the fetal alcohol syndrome recognized by the Greeks and Romans?
Ancient Greek and Roman philosophers/scientists are frequently quoted as expressing an awareness of potential harm associated with drinking during pregnancy. However, the statements attributed to these authors were not made by them. Instead, they are interpretations, presented in the form of verbatim statements, of their views relating to procreation. Although they did have something to say about the role of alcohol in procreation, it was the effects of drinking on the male body at the time of conception, and especially alcohol's effects on male body temperature, that concerned them. A cold body at the time of conception was believed to enhance the likelihood of conceiving a female, which to the Greeks and Romans was a 'deformity'. (+info)
Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome.
The deleterious effects of ethanol on the developing human brain are poorly understood. Here it is reported that ethanol, acting by a dual mechanism [blockade of N-methyl-D-aspartate (NMDA) glutamate receptors and excessive activation of GABA(A) receptors], triggers widespread apoptotic neurodegeneration in the developing rat forebrain. Vulnerability coincides with the period of synaptogenesis, which in humans extends from the sixth month of gestation to several years after birth. During this period, transient ethanol exposure can delete millions of neurons from the developing brain. This can explain the reduced brain mass and neurobehavioral disturbances associated with human fetal alcohol syndrome. (+info)
Identification and evaluation of mental retardation.
Mental retardation in young children is often missed by clinicians. The condition is present in 2 to 3 percent of the population, either as an isolated finding or as part of a syndrome or broader disorder. Causes of mental retardation are numerous and include genetic and environmental factors. In at least 30 to 50 percent of cases, physicians are unable to determine etiology despite thorough evaluation. Diagnosis is highly dependent on a comprehensive personal and family medical history, a complete physical examination and a careful developmental assessment of the child. These will guide appropriate evaluations and referrals to provide genetic counseling, resources for the family and early intervention programs for the child. The family physician is encouraged to continue regular follow-up visits with the child to facilitate a smooth transition to adolescence and young adulthood. (+info)
Effects of prenatal alcohol exposure on social behavior in humans and other species.
Alcohol exposure during development causes central nervous system alterations in both humans and animals. Although the most common behavioral manifestation of these alterations is a reduction in cognitive abilities, it is becoming increasingly apparent that deficits in social behavior may be very prevalent sequelae of developmental alcohol exposure. In infancy and early childhood, deficits in attachment behavior and state regulation are seen in both alcohol-exposed people and animals, suggesting that these changes are largely the result of the alcohol exposure rather than maternal behavior. In the periadolescent period, people exposed to alcohol during development show a variety of difficulties in the social domain as measured by checklists filled out by either a parent or teacher. Rats exposed to alcohol during development show changes in play and parenting behaviors. In adulthood, prenatal alcohol exposure is related to high rates of trouble with the law, inappropriate sexual behavior, depression, suicide, and failure to care for children. These high rates all suggest that there may be fundamental problems in the social domain. In other animals, perinatal alcohol exposure alters aggression, active social interactions, social communication and recognition, maternal behavior, and sexual behavior in adults. In conclusion, research suggests that people exposed to alcohol during development may exhibit striking changes in social behavior; the animal research suggests that these changes may be largely the result of the alcohol insult and not the environment. (+info)
On categorizations in analyses of alcohol teratogenesis.
In biomedical scientific investigations, expositions of findings are conceptually simplest when they comprise comparisons of discrete groups of individuals or involve discrete features or characteristics of individuals. But the descriptive benefits of categorization become outweighed by their limitations in studies involving dose-response relationships, as in many teratogenic and environmental exposure studies. This article addresses a pair of categorization issues concerning the effects of prenatal alcohol exposure that have important public health consequences: the labeling of individuals as fetal alcohol syndrome (FAS) versus fetal alcohol effects (FAE) or alcohol-related neurodevelopmental disorder (ARND), and the categorization of prenatal exposure dose by thresholds. We present data showing that patients with FAS and others with FAE do not have meaningfully different behavioral performance, standardized scores of IQ, arithmetic and adaptive behavior, or secondary disabilities. Similarly overlapping distributions on measures of executive functioning offer a basis for identifying alcohol-affected individuals in a manner that does not simply reflect IQ deficits. At the other end of the teratological continuum, we turn to the reporting of threshold effects in dose-response relationships. Here we illustrate the importance of multivariate analyses using data from the Seattle, Washington, longitudinal prospective study on alcohol and pregnancy. Relationships between many neurobehavioral outcomes and measures of prenatal alcohol exposure are monotone without threshold down to the lowest nonzero levels of exposure, a finding consistent with reports from animal studies. In sum, alcohol effects on the developing human brain appear to be a continuum without threshold when dose and behavioral effects are quantified appropriately. (+info)
Fetal alcohol syndrome: the origins of a moral panic.
Since its discovery almost 30 years ago, the fetal alcohol syndrome (FAS) has been characterized in the USA, as a major threat to public health. In part because FAS resonated with broader social concerns in the 1970s and 1980s about alcohol's deleterious effect on American society and about a perceived increase in child abuse and neglect, it quickly achieved prominence as a social problem. In this paper, we demonstrate that, as concern about this social problem escalated beyond the level warranted by the existing evidence, FAS took on the status of a moral panic. Through examples taken from both the biomedical literature and the media about drinking during pregnancy, we illustrate the evolution of this development, and we describe its implications, particularly how it has contributed to a vapid public policy response. (+info)