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

Exposure to ethanol during development induces severe brain damage resulting in a number of CNS dysfunctions including microencephaly and mental retardation in humans and in laboratory animals. The most vulnerable period to ethanol neurotoxicity coincides with the peak of brain growth spurt. Recently, neurotrophic factors and/or their signal transduction pathways have been reported as a potential relevant target for the developmental neurotoxicity of ethanol. The present studies were designed to investigate the effects of ethanol given in various developmental phases during the brain growth spurt in rats. Rat pups were assigned to the three treatment groups and treated with 5 g/kg of ethanol for three days, on postnatal days (PND) 2-4, 6-8 or 13-15. Whole brain weights were reduced only in the PND 6-8 group concurrently with the reduction of GDNF mRNA in cortex in this group. BDNF mRNA expression was reduced in both the PND 6-8 and 13-15 groups, while mRNA expressions of NT-3 and NGF were unchanged in all three groups. Phospho-Akt level was mostly reduced in the PND 6-8 group. Both phospho-MAPK and p-70S6 kinase levels were decreased in all groups whereas no changes were observed in either phospho-PKCzeta or CREB level. The phosphorylation of Akt was immediately inhibited after single administration of ethanol, and its inhibition was correlated with variations in blood ethanol concentration. These findings suggest that GDNF and the phosphorylation of Akt play a possible key role in the ethanol-induced developmental neurotoxicity.
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PMID:Effects of postnatal ethanol exposure at different developmental phases on neurotrophic factors and phosphorylated proteins on signal transductions in rat brain. 1835 98

Fetal alcohol syndrome is a leading cause of mental retardation, but mechanisms of alcohol-associated brain damage remain elusive. Chronic alcohol exposure attenuates fetal and neonatal hypoxic cerebral vasodilation in sheep. We therefore hypothesized that alcohol could alter development of cerebrovascular responses to adenosine, a putative mediator of hypoxic cerebral vasodilation. The objective of this study was to examine the effect of earlier fetal alcohol exposure on later reactivity to adenosine in fetal sheep cerebral arterioles. Penetrating intracerebral arterioles were harvested from the brains of third trimester fetal sheep previously exposed in the second trimester to maternal alcohol "binges" (1.5 g/kg IV over 90 min, 5 days/week for 4 weeks) or same-volume saline infusions. Arterioles were cannulated with a micropipette system and luminally pressurized. Fetal alcohol exposure did not affect spontaneous myogenic tone, but enhanced the dilator response of penetrating arterioles to extraluminal acidosis (pH 6.8). Alcohol exposure also resulted in an increase in maximal vessel response to CGS-21680, an adenosine A2A receptor agonist, but did not alter the concentration-dependent response curves to adenosine. Our results suggest that earlier alcohol exposure does not impair the subsequent responsiveness of fetal cerebral arterioles to vasodilator agents. Thus, alteration in cerebral vascular response to hypoxia in fetal sheep may not be attributed to changes in vascular reactivity to adenosine.
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PMID:Effects of binge alcohol exposure in the second trimester on intracerebral arteriolar function in third trimester fetal sheep. 1864 Jun 64

Ethanol exposure during pregnancy is one of the major causes of mental retardation in western countries by inducing fetal-alcohol-like-syndromes. Red wine is known to contain ethanol but also compounds with putative antioxidant properties. It has also been shown that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are severely affected by ethanol during prenatal and postnatal life. The aim of the current study was to investigate in male CD1 mice brain alterations in NGF and BDNF due to chronic early exposure to ethanol solution (11 vol%) or to red wine at the same alcohol concentration starting from 60 days before pregnancy up to pups weaning. Data revealed no differences between groups of dams in pregnancy duration, neither in pups delivery, pups mortality and sex ratio. Data also showed that adult animals exposed to only ethanol had disrupted levels of both NGF and BDNF in the hippocampus and other brain areas. This profile was associated with impaired ChAT immunopositivity in the septum and Nuclei Basalis and with altered cognition and emotional behavior. Quite interestingly mice exposed to red wine had no change in the behavior or in ChAT immunopositivity but a decrease in hippocampal BDNF and a mild NGF decrease in the cortex. Also NGF-induced neuritic outgrowth in PC-12 cells was still present when exposed to red wine but not when exposed to ethanol solution only. Data suggest differences in ethanol-induced neurotoxicity between red wine and ethanol solution only.
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PMID:Early exposure to ethanol but not red wine at the same alcohol concentration induces behavioral and brain neurotrophin alterations in young and adult mice. 1910 Feb 86

Ethanol is a potent teratogen for the developing central nervous system (CNS), and fetal alcohol syndrome (FAS) is the most common nonhereditary cause of mental retardation. Ethanol disrupts neuronal differentiation and maturation. It is important to identify agents that provide neuroprotection against ethanol neurotoxicity. Using an in vitro neuronal model, mouse Neuro2a (N2a) neuroblastoma cells, we demonstrated that ethanol inhibited neurite outgrowth and the expression of neurofilament (NF) proteins. Glycogen synthase kinase 3beta (GSK3beta), a multifunctional serine/threonine kinase negatively regulated neurite outgrowth of N2a cells; inhibiting GSK3beta activity by retinoic acid (RA) and lithium induced neurite outgrowth, while over-expression of a constitutively active S9A GSK3beta mutant prevented neurite outgrowth. Ethanol inhibited neurite outgrowth by activating GSK3beta through the dephosphorylation of GSK3beta at serine 9. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family rich in many edible berries and other pigmented fruits, enhanced neurite outgrowth by promoting p-GSK3beta(Ser9). More importantly, C3G reversed ethanol-mediated activation of GSK3beta and inhibition of neurite outgrowth as well as the expression of NF proteins. C3G also blocked ethanol-induced intracellular accumulation of reactive oxygen species (ROS). However, the antioxidant effect of C3G appeared minimally involved in its protection. Our study provides a potential avenue for preventing or ameliorating ethanol-induced damage to the developing CNS.
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PMID:Cyanidin-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth: role of glycogen synthase kinase 3 Beta. 1938 66

Fetal alcohol syndrome is a leading cause of mental retardation. The neuropathology found in patients with fetal alcohol syndrome overlaps with those with mutations in the gene for cell adhesion molecule (L1). We have previously shown that L1-mediated neurite outgrowth and L1 activation of extracellular receptor kinases 1/2 are inhibited at low concentrations of ethanol. One possible mechanism for this effect is through disruption of a tyrosine-based sorting signal, Y(1176)RSLE, on the cytoplasmic domain of L1. Our goal was to determine if ethanol inhibited the sorting signal or its phosphorylation state. Using cerebellar granule neurons and dorsal root ganglion neurons, we found that ethanol had no effect on L1 distribution to the growth cone or its ability to be expressed on the cell surface as determined by confocal microscopy. In cerebellar granule neurons, clustering of L1 resulted in increased dephosphorylation of Y(1176), increased L1 tyrosine phosphorylation, and an increase in the activation of pp60(src) as measured by immunoblot. All changes were inhibited by 25 mM ethanol. Using PP2 to inhibit pp60(src) activation resulted in inhibition of increases in L1 tyrosine and extracellular receptor kinases 1/2 phosphorylation, and Y(1176) dephosphorylation. We conclude that ethanol disrupts L1 trafficking/signaling following its expression on the surface of the growth cone, and prior to its activation of pp60(src).
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PMID:Ethanol inhibits L1 cell adhesion molecule tyrosine phosphorylation and dephosphorylation and activation of pp60(src). 1945 8

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by seizures, mental retardation, and various hamartomatous lesions, including renal angiomyolipoma (AML) and pulmonary lymphangioleiomyomatosis. A 22-year-old woman with TSC presented with multiple renal AMLs exceeding 4 cm in diameter. She underwent two transcatheter embolization procedures with a mixture of ethanol and iodized oil. She complained of dyspnea and minor hemoptysis 4 and 6 hours after the procedure. Findings on chest radiographs and computed tomographic images were indicative of pulmonary edema. The patient was treated with conservative therapy. The possible causes of the pulmonary edema are discussed in the text.
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PMID:Pulmonary edema as a complication of transcatheter embolization of renal angiomyolipoma in a patient with pulmonary lymphangioleiomyomatosis due to tuberous sclerosis complex. 1946 8

Alcohol consumption during pregnancy is a significant public health problem and may result in a wide range of adverse outcomes for the child. The developing central nervous system (CNS) is particularly susceptible to ethanol toxicity. Children with fetal alcohol spectrum disorders (FASD) have a variety of cognitive, behavioral, and neurological impairments. FASD currently represents the leading cause of mental retardation in North America ahead of Down syndrome and cerebral palsy. Ethanol exposure during development causes multiple abnormalities in the brain such as permanent loss of neurons, ectopic neurons, and alterations in synaptogenesis and myelinogenesis. These alcohol-induced structural alterations in the developing brain underlie many of the behavioral deficits observed in FASD. The cellular and molecular mechanisms of ethanol neurotoxicity, however, remain unclear. Ethanol elicits cellular stresses, including oxidative stress and endoplasmic reticulum stress. Glycogen synthase kinase 3beta (GSK3beta), a multifunctional serine/threonine kinase, responds to various cellular stresses. GSK3beta is particularly abundant in the developing CNS, and regulates diverse developmental events in the immature brain, such as neurogenesis and neuronal differentiation, migration, and survival. Available evidence indicates that the activity of GSK3beta in the CNS is affected by ethanol. GSK3beta inhibition provides protection against ethanol neurotoxicity, whereas high GSK3beta activity/expression sensitizes neuronal cells to ethanol-induced damages. It appears that GSK3beta is a converging signaling point that mediates some of ethanol's neurotoxic effects.
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PMID:GSK3beta in ethanol neurotoxicity. 1950 62

Heavy alcohol exposure produces profound damage to the developing central nervous system (CNS) as well as the adult brain. Children with fetal alcohol spectrum disorders (FASD) have a variety of cognitive, behavioral, and neurological impairments. FASD currently represents the leading cause of mental retardation. Excessive alcohol consumption is associated with Wernicke-Korsakoff syndrome (WKS) and neurodegeneration in the adult brain. Although the cellular/molecular mechanism underlying ethanol's neurotoxicity has not been fully understood, it is generally believed that oxidative stress plays an important role. Identification of neuroprotective agents that can ameliorate ethanol neurotoxicity is an important step for developing preventive/therapeutic strategies. Targeting ethanol-induced oxidative stress using natural antioxidants is an attractive approach. Anthocyanins, a large subgroup of flavonoids present in many vegetables and fruits, are safe and potent antioxidants. They exhibit diverse potential health benefits including cardioprotection, anti-atherosclerotic activity, anti-cancer, anti-diabetic, and anti-inflammation properties. Anthocyanins can cross the blood-brain barrier and distribute in the CNS. Recent studies indicate that anthocyanins represent novel neuroprotective agents and may be beneficial in ameliorating ethanol neurotoxicity. In this review, we discuss the evidence and potential of anthocyanins in alleviating ethanol-induced damage to the CNS. Furthermore, we discuss possible underlying mechanisms as well as future research approaches necessary to establish the therapeutic role of anthocyanins.
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PMID:Anthocyanins: are they beneficial in treating ethanol neurotoxicity? 1959 Sep 29

Alcohol consumption during pregnancy is a major cause of mental retardation in Western countries. Fetal alcohol syndrome (FAS) is mainly characterized by pre- and postnatal stunted growth, neurocognitive disorders, and facial dysmorphism. It compromises the intellectual and behavioral prognosis of the child. Prevention tools exist, through better information of health professionals, for optimal care of high-risk women before, during, and after pregnancy, which would decrease the incidence of SAF in the future.
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PMID:[Alcohol and pregnancy]. 1968 4

Alcohol affects approximately 1% (40,000) of new born infants each year and is the main preventable cause of mental retardation in the US. Ethanol alters cell signaling and promotes apoptosis and differentiation. Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family of growth factors, has been reported to prevent apoptosis and differentiation. We treated human embryonic stem cells (hESCs) with ethanol (20 mM) to reflect casual drinking, with and without HB-EGF to measure its ability to prevent ethanol-induced apoptosis and differentiation. Apoptosis was measured by DNA fragmentation (terminal dUTP nick-end labeling assays) and activated caspase-3, while differentiation was accessed by SSEA-1 and OCT-3/4; western blotting assessed MAPK signaling. HB-EGF reduced SSEA-1 and elevated OCT-3/4, while reducing the amount of activated caspase-3 and DNA fragmentation. Western blot analysis showed HB-EGF prevents ethanol from altering MAPK phosphorylation. This data suggests that ethanol-induced apoptosis was reduced by HB-EGF, while hESC pluripotency was maintained.
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PMID:Heparin binding epidermal growth factor-like growth factor reduces ethanol-induced apoptosis and differentiation in human embryonic stem cells. 1991 24


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