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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent data have shown that the structure and function of layer V pyramidal neurons, e.g. corticospinal neurons, is altered by prenatal exposure to ethanol. We examined the effect of ethanol on the ultrastructure of layer V in somatosensory cortex. Timed pregnant rats were fed a diet containing 6.7% (v/v) ethanol (E) or pair-fed a nutritionally matched control diet (C). Thirty-day-old offspring of these mothers were prepared by standard electron microscopic techniques. The somata of pyramidal and local circuit neurons and the neuropil were analysed. Prenatal exposure to ethanol induced alterations in the somata of both populations of neurons. The parallel stacking of cisternae characteristic of C-treated rats was disorganized in E-treated rats. Moreover, the Golgi complex and lysosomes occupied a larger fraction of the somata of E-treated rats. The number and frequency of symmetric axosomatic synapses, but not asymmetric axosomatic synapses, formed by both types of neurons were significantly greater in E-treated rats. Gestational exposure to ethanol produced a variety of changes in the neuropil. Dendrites, particularly dendritic shafts, occupied less space in E-treated rats. In contrast, axons accounted for significantly more of the neuropil in E-treated rats than in controls. This increase in axonal space was due to a significantly greater coverage by non-myelinated axons and a significantly smaller coverage by myelinated axons in E-treated rats than in C-treated rats. Although the overall frequency of synapses was similar in both treatment groups, there were significantly more asymmetric synapses in E-treated rats, and most of these were axospinous synapses. These differences may contribute to documented physiological changes such as the lower rate of glucose utilization in layer V of somatosensory cortex of E-treated rats and they may underlie the mental retardation which is characteristic of children with foetal alcohol syndrome.
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PMID:Effect of prenatal exposure to ethanol on the ultrastructure of layer V of mature rat somatosensory cortex. 262 73

We investigated the effects of ethanol exposure on the shape of the cell and the morphology of intermediate filaments (IF) of cortical astrocytes in primary culture. The content and distribution of glial fibrillary acidic protein (GFAP), the major component of glial IF, was assessed using an anti-GFAP monoclonal antibody and fluorescence scanning densitometry together with quantitative pre- and post-embedding immunogold electron microscopy. The astrocytes were from 21-day-old fetuses obtained from both control and chronic alcoholic rats and were cultured for 28 days in the absence or presence of ethanol (25 mM). The main findings were: (a) ethanol-exposed astrocytes failed to develop processes or to acquire a filamentous IF distribution pattern; (b) these cells showed less GFAP than astrocytes without alcohol; (c) ethanol interfered with the reorganization of the anti-GFAP binding sites from clustered to random; and (d) astrocytes from alcohol-exposed fetuses cultured in the absence of ethanol also showed these alterations, suggesting initial damage to astrocyte precursor cells. Since the glial filaments play a crucial role in creating a scaffolding that guides neuronal migration, the effect of ethanol on astrocyte IF may possibly be correlated with the mechanisms underlying mental retardation and motor dysfunction which are characteristics of fetal alcohol syndrome.
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PMID:Effects of prolonged ethanol exposure on the glial fibrillary acidic protein-containing intermediate filaments of astrocytes in primary culture: a quantitative immunofluorescence and immunogold electron microscopic study. 264 42

The inhibition of fetal brain growth resulting from in utero ethanol exposure may impair central nervous system (CNS) development and thereby result in mental retardation. Studies of ethanol-induced brain hypoplasia using chick embryos have shown that the early development of the chick is significantly growth inhibited by a single dose of ethanol (1.0 g/kg) given at the start of incubation (day 0). However, this level of ethanol exposure has been reported to have no effect on chick weight measured at hatching, suggesting that the weights of ethanol-treated chicks were regained during their development. The present experiments were undertaken to determine the biochemical changes associated with the varying growth rates believed to occur in the alcohol-treated embryos. The results indicated that between days 5 and 8 of development, the rates of DNA and protein synthesis (measured as radioactive thymidine and leucine incorporation, respectively) were inhibited by ethanol. The growth inhibition was highly correlated with blood alcohol content and there were associated increases in brain prostaglandin E (PGE) levels relative to vehicle-treated embryos. Further, there was a significant, inverse correlation between brain cyclic AMP content and individual brain weight. By day 10, the ethanol-treated embryos remained smaller than controls but their rates of DNA and protein synthesis were comparable to those of control animals. The normal rates of synthesis observed on day 10 appeared to correlate with clearance of the ethanol dose and with restoration of normal brain levels of PGE relative to 10-day vehicle-dosed embryos.
Drug Alcohol Depend 1987 Nov 30
PMID:Brain growth during ethanol-induced hypoplasia. 283 89

Fetal injury associated with maternal ethanol ingestion is a major cause of congenital anomalies and mental retardation. Studies with animals suggest that acetaldehyde, the primary hepatic oxidative metabolite of ethanol, may contribute to fetal damage. It is not known, however, whether acetaldehyde reaches the human fetus, either by placental production or transfer. Studies utilizing the perfused human placental cotyledon show that the human placenta oxidizes ethanol to acetaldehyde, releasing it into the fetal perfusate. Moreover, when acetaldehyde is present in the maternal perfusate, it is transferred to the fetal side, reaching approximately 50 percent of the maternal level. These findings suggest that the human placenta may play a pivotal role in the pathophysiology of ethanol-associated fetal injury.
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PMID:Acetaldehyde production and transfer by the perfused human placental cotyledon. 317 52

This study was designed to compare manifestations of FAS in the offspring of lower and upper middle class chronic alcoholic mothers, and to compare these offspring with those of nonalcoholic controls. There was highly significant difference in the incidence of FAS offspring between upper middle and lower class alcoholic mothers, 4.5% versus 70.9% respectively. Mean weight, length, and head circumference at birth in children of upper middle class alcoholic women was -ISD, those of lower class alcoholic women fell into -2SD. All other parameters, congenital malformation rate, failure to thrive, mental retardation were also significantly greater in children of lower class alcoholic women (p less than or equal to .01). Attention deficit disorder was found in 21% of upper middle class offspring of alcoholic women as compared to 71% in the children of the lower socioeconomic group (p less than or equal to .01).
Adv Alcohol Subst Abuse 1987
PMID:The influence of socioeconomic factors on the occurrence of fetal alcohol syndrome. 342 75

We examined the developing synaptic junctions in the rat frontal cortex in cases of fetal alcohol syndrome, the objective being to determine the synapse-mental retardation relationship. On day 21 of gestation, the ultrastructural synaptic junction revealed no obvious differences between the ethanol-exposed and control rats; however, the number of synapses in ethanol-exposed rats was one third that of the controls. The possible relationship between synaptic density in the frontal cortex and mental development has to be considered.
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PMID:Decreased density of synaptic formation in the frontal cortex of neonatal rats exposed to ethanol in utero. 350 16

The world-wide incidence of the fetal alcohol syndrome (FAS) is 1.9 per 1000 live births. Incidence rates vary considerably, however, depending on study site. Mental retardation is a cardinal feature of FAS and is now recognized as the leading known cause of mental retardation in the Western world. Conservatively estimated for the United States, the economic cost associated with FAS-related growth retardation, surgical repair of organic anomalies (e.g. cleft palate, Tetralogy of Fallot), treatment of sensorineural problems, and mental retardation, is +321 million per year. FAS-related mental retardation alone may account for as much as 11% of the annual cost for all mentally retarded institutionalized residents in the United States. Current treatment costs for FAS-related problems are about 100 times federal funding for FAS research necessary to develop cost-effective early identification and prevention strategies.
Drug Alcohol Depend 1987 Jan
PMID:Incidence of fetal alcohol syndrome and economic impact of FAS-related anomalies. 354 31

This article reviews the effects of alcohol on male and female gonads and hormonal levels; it further discusses the use of ethanol during pregnancy and its teratogenic effect on the fetus. Impotence is a common result of acute alcoholism, and testicular atrophy, infertility, and decreased libido are associated with alcoholism 70-80% of the time. In addition, alcohol consumption produces significant spermatozoal morphological changes involving breakage of the sperm head, distention of the midsection, and curling of its tail. Seminiferous tubules are filled mostly with spermatids that undergo degeneration and result in aspermia. Acute ethanol intoxication is accompanied by decreased plasma testosterone levels and a surge of luteinizing hormone. Ethanol appears to have a dual effect: locally on the gonads and centrally on the hypothalamus-pituitary axis, causing an adverse effect on spermatogenesis. Less is known about the effects of alcohol on the female reproductive function; however, inhibition of ovulation and a significant reduction of plasma estradiol and progesterone levels has been noted in rats following ethanol administration. Alcohol consumption during pregnancy is the most frequent known teratogenic cause of mental retardation. Infants most severely affected by maternal alcohol abuse during gestation possess a number of dysmorphic anomalies termed fetal alcohol syndrome. The abnormalities most typically associated with alcohol teratogenicity can be grouped into 4 categories: growth deficiencies, central nervous system dysfunctions, craniofacial abnormalities, and other major and minor malformations. The effects of maternal alcohol consumption on the fetus are independent of maternal nutritional status and smoking history. Alcohol abuse during pregnancy occurs in 2-13% of US women, and these women have a 50-70% chance of delivering an infant with a serious abnormality.
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PMID:Alcohol and reproductive function: a review. 354 7

The distribution and the time of origin of corticospinal neurons were examined in rats prenatally exposed to ethanol and in control rats. The distribution of corticospinal neurons was determined by tracing the retrograde transport of horseradish peroxidase (HRP) from an injection site in the cervical spinal cord. In control rats, HRP-positive neurons were distributed in layer Vb throughout motor area 4, rostral motor area 6/8, dorsal somatosensory area 3, caudal somatosensory area 2, and various "association" regions including parietal areas 14, 39, and 40, occipital areas 18a and 18b, cingulate areas 24a and 24b, and prefrontal area 32. In ethanol-exposed rats, the distribution of retrogradely labeled neurons was similar to control animals with three notable exceptions: (1) HRP-positive neurons were evident throughout the rostrocaudal extent of area 6/8; (2) occasionally ectopic labeled neurons were identified in the supragranular layers, layers Va and Vc, and superficial layer VI; and (3) the density of HRP-labeled neurons and the ratio of labeled neurons to the total number of neurons in areas 4, 6/8, 3 and 2 were significantly greater (20-48%) in ethanol-exposed rats than in controls. There was, however, no intergroup difference in the area of the cell bodies of HRP-positive neurons. Taken together, these findings indicate that ethanol exposure resulted in an increased number of corticospinal neurons. The time of origin of corticospinal neurons was determined by using a technique that combined tritiated thymidine autoradiography and retrograde transport of HRP. In control animals, HRP-positive neurons were double labeled by an injection of tritiated thymidine on gestational day (GD) 15, 16, or 17. In ethanol-exposed rats, corticospinal neurons were generated on GD 16, 17, and 18, the late-generated ones being distributed in caudal area 6/8. These intergroup differences represent a persisting ethanol-induced alteration of cortical structure that may underlie motor dysfunction and mental retardation in fetal alcohol-affected offspring. Moreover, the increase in the number and the delay in the time of origin of corticospinal neurons suggest that the normal process of paring down exuberant corticospinal projections may be affected by prenatal exposure to ethanol.
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PMID:Effect of prenatal exposure to alcohol on the distribution and time of origin of corticospinal neurons in the rat. 355 95

Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) are preventable forms of mental retardation and developmental disability caused by heavy prenatal alcohol exposure. Our best evidence of the overall prevalence of FAS is around 1 in 750 live births, but this figure will vary according to the drinking habits of the community and the diagnostic skills and interests of local physicians. It is likely that many infants are born with FAS or FAE, are never recognized as such, and are never properly diagnosed or evaluated. Other diagnoses that are sometimes confused with FAS include Noonan syndrome and William syndrome. More often, children with milder FAS or FAE go unrecognized. Careful evaluation of possible maternal alcohol abuse during pregnancy can be an important factor in differential diagnosis and proper case management. Alcohol is a teratogenic drug that can produce a wide variety of deficits from prenatal exposure, depending on the dose, timing, and conditions of exposure, as well as on individual differences in sensitivity on the part of the mother and the child. Not all children who are exposed are affected. Perhaps 30-40% of the children of chronic alcoholic mothers who were drinking during pregnancy will have FAS. These children are at high risk for mental retardation or developmental disability. Even within this group, however, there can be large individual differences in eventual outcome. Prognosis involves an interaction between the extent of the damage and the stability and structure of the environment. Children whose mothers were abusing alcohol during pregnancy can be at risk for various learning and attentional problems even without FAS, but in the absence of morphologic effects, the diagnostic and prognostic picture is less clear. Systematic efforts toward both prevention and intervention can assure that each child develops to his or her own best potential.
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PMID:Fetal alcohol. Teratogenic causes of developmental disabilities. 361 65


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