Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical and biochemical data on 13 patients with Batten's syndrome are described. Clinically the disease was characterized by progressive maental and somatic deterioration. Initially, vision loss was found between the ages 4 and 8 years. This was associated with 1 or 2 years of normal school attendance followed by attendance at a school for mentally retarded from the age of 8 to 11; then warding was established at a school for blind children and later on a hospital for epileptic patients when seizures and mental retardation made hospitalization necessary. Biochemically, an increased peroxidation rate was revealed in peripheral thrombocytes. This abnormality was associated with a significant decrease in peroxidase activity of leucocytes assayable with p-phenylenediamine, but not with Guajacol. The peroxidase defect seemed to concern an azide-resistant peroxidase. However, in serum the glutathione peroxidase was only found insignificantly decreased.
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PMID:Clinical, social and biochemical studies on Batten's syndrome, alias Spielmeyer-Vogot or Stengel's Syndrome. 87 40

Down's Syndrome (DS), the most frequent of congenital birth defects, results from the trisomy of the chromosome numbered 21 in all cells of affected patients. This disease is characterized by developmental anomalies, mental retardation and features of rapid aging, particularly in the brain where the occurrence of Alzheimer's disease (AD) is observed in all trisomy 21 patients over the age of 35. Elucidation of the biological mechanisms leading to brain aging in DS might provide new insight into the understanding of brain aging and AD in normal people. Copper-zinc superoxide dismutase (CuZnSOD) is one of the genes encoded by chromosome 21. As a consequence of gene dosage excess, CuZnSOD activity and protein are increased by 50% in all DS tissues. The level of CuZnSOD protein and mRNA is particularly high in hippocampal pyramidal neurons susceptible to degenerative processes in AD and in dopaminergic melanized-neurons vulnerable in Parkinson's disease. Increased CuZnSOD activity in these age-related neurodegenerative disorders might result in H2O2 overproduction and subsequently promote peroxidative damages within cells. Increase of seleno-dependent glutathione peroxidase (Se-GPx) in DS cells supports this concept. In order to test this hypothesis, cell and animal models of CuZnSOD overexpression have been designed. In cells transfected with the human CuZnSOD gene, and increased Se-GPx activity is observed, a situation which mimics DS. In mice transgenic for the human CuZnSOD, the expression pattern of the transgene in the brain is similar to that in humans, and we can observe an increased peroxidation in this tissue. These data, like others in the literature, support the hypothesis that excess CuZnSOD induces an imbalance in the regulation of oxygen-derived free radical production which might result in peroxidative brain damage and possibly contribute to accelerated aging and age-related neuropathology.
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PMID:Cellular clones and transgenic mice overexpressing copper-zinc superoxide dismutase: models for the study of free radical metabolism and aging. 145 Jun 8

To protect against reactive oxygen species, prokaryotic and eukaryotic cells have developed an antioxidant defence mechanism where O2- is converted to H2O2 by superoxide dismutase (Sod), and in a second step, H2O2 is converted to H2O by catalase (Cat) and/or glutathione peroxidase (Gpx). If Sod levels are increased without a concomitant Gpx increase, then the intermediate H2O2 accumulates. This intermediate could undergo the Fenton's reaction, generating hydroxyl radicals which may lead to lipid peroxidation in cells. In this study, we investigate the expression of Sod1, Gpx1 and susceptibility to lipid peroxidation during the aging process in mouse brains. We demonstrate that the mRNA levels and enzyme activity of Sod1 are higher in brains from adult mice compared to neonatal mice. Furthermore, we show that a linear increase in Sod1 mRNA and enzyme activity occurs with aging (1-100 weeks). On the contrary, we find that the mRNA and enzyme activity for Gpx1 does not increase with aging in mouse brains. In addition, our results demonstrate that the susceptibility of murine brains to lipid peroxidation increases with aging. The data in this study are consistent with the notion that reactive oxygen species may contribute to the aging process in mammalian brains. These results are discussed in relation to the normal aging process in mammals, and to the premature aging and mental retardation in Down syndrome.
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PMID:Cu/Zn superoxide dismutase mRNA and enzyme activity, and susceptibility to lipid peroxidation, increases with aging in murine brains. 159 44

Down syndrome is the most common cause of mental retardation, affecting 1 in 700-800 liveborn infants. Although numerous biochemical abnormalities accompanying the syndrome have not yet been completely clarified, the antioxidant defense system enzymes have shown to be altered due to increased gene dosage on chromosome 21 and overproduction of superoxide dismutase (SOD-1 or Cu/Zn SOD). The purpose of this study was to investigate the activities of SOD-1 and glutathione peroxidase (GSH-Px) enzymes and the levels of their cofactors zinc (Zn), copper (Cu) and selenium (Se) in plasma of 20 Down syndrome patients. In comparison with age and sex-matched controls (n = 15), plasma GSH-Px, SOD, and Cu levels were significantly decreased in the patient group, but Zn and Se concentrations remained unchanged.
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PMID:Antioxidative metabolism in Down syndrome. 982 38

Tissue accumulation of L-phenylalanine (Phe) is the biochemical hallmark of human phenylketonuria (PKU), an inherited metabolic disorder clinically characterized by mental retardation and other neurological features. The mechanisms of brain damage observed in this disorder are poorly understood. In the present study we investigated some oxidative stress parameters in the brain of rats with experimental hyperphenylalaninemia. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in the brain of the animals. We observed that chemiluminescence is increased and TRAP is reduced in the brain of hyperphenylalaninemic rats. Similar data were obtained in the in vitro experiments using Phe at various concentrations. CAT activity was significantly inhibited by Phe in vitro and in vivo, whereas GSH-Px activity was reduced in vivo but not in vitro and SOD activity was not altered by any treatment. The results indicate that oxidative stress may be involved in the neuropathology of PKU. However, further studies are necessary to confirm and extend our findings to the human condition and also to determine whether an antioxidant therapy may be of benefit to these patients.
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PMID:Experimental hyperphenylalaninemia provokes oxidative stress in rat brain. 1199 85

Homocystinuria is an inherited metabolic disease characterized biochemically by increased blood and brain levels of homocysteine caused by severe deficiency of cystathionine beta-synthase activity. Affected patients present mental retardation, seizures, and atherosclerosis. Oxidative stress plays an important role in the pathogenesis of many neurodegenerative and vascular diseases, such Alzheimer's disease, stroke, and atherosclerosis. However, the mechanisms underlying the neurological damage characteristic of homocystinuria are still poorly understood. To evaluate the involvement of oxidative stress on the neurological dysfunction present in homocystinuria, we measured thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and total radical-trapping antioxidant potential (TRAP) and antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) in rat hippocampus in the absence (controls) or in the presence of homocysteine (10-500 microM) in vitro. We demonstrated that homocysteine significantly increases TBARS and decreases TRAP, both in a dose-dependent manner, but did not change antioxidant enzymes. Our results suggest that oxidative stress is involved in the neurological dysfunction of homocystinuria. However, further studies are necessary to confirm and extend our findings to the human condition and also to determine whether antioxidant therapy may be of benefit to these patients.
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PMID:In vitro effect of homocysteine on some parameters of oxidative stress in rat hippocampus. 1282 33

Hyperprolinemia type II is an autosomal recessive disorder caused by the severe deficiency of delta(1)-pyrroline-5-carboxylate dehydrogenase activity leading to tissue accumulation of proline (Pro). Most patients detected so far show neurological manifestations including epilepsy and mental retardation, whose pathophysiology is not yet fully established. In the present study, we determined the in vivo and in vitro effects of Pro on some parameters of oxidative stress, namely chemiluminescence, total radical-trapping antioxidant potential (TRAP) and the activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) from cerebral cortex of 29-day-old Wistar rats. Results showed that acute administration of Pro provoked a significant increase of chemiluminescence and a decrease of TRAP, whereas chronic administration of the metabolite did not alter these parameters. Furthermore, in vitro brain exposure to Pro resulted in increased chemiluminescence and decreased TRAP at Pro concentrations similar to those observed in tissues of hyperprolinemic patients (0.5-1.0 mM). As regards to the antioxidant enzymes, acute injection of Pro significantly decreased CAT activity and did not alter SOD and GSH-Px activities, whereas chronic Pro administration provoked a significant increase of CAT activity, a decrease of GSH-Px activity and did not modify SOD activity. Furthermore, CAT, GSH-Px and SOD activities were not affected by the presence of Pro in the incubation medium. The data indicate that Pro induces oxidative stress in vivo and in vitro, which may be involved in the brain dysfunction observed in hyperprolinemic patients.
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PMID:In vivo and in vitro effects of proline on some parameters of oxidative stress in rat brain. 1457 90

Histidinemia is an inherited metabolic disorder caused by deficiency of histidase activity, which leads to tissue accumulation of histidine and its derivatives. Affected patients usually present with speech delay and mental retardation, although asymptomatic patients have been reported. Considering that the pathophysiology of the neurological dysfunction of histidinemia is not yet understood and since histidine has been considered a pro-oxidant agent, in the present study we investigated the effect of histidine and one of its derivatives, l-beta-imidazolelactic acid, at concentrations ranging from 0.1 to 10 mM, on various parameters of oxidative stress in cerebral cortex of 30-day-old Wistar rats. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), thiobarbituric acid reactive substances (TBA-RS), and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured in tissue homogenates in the presence of l-histidine or l-beta-imidazolelactic acid. We observed that l-histidine provoked an increase of chemiluminescence and a reduction of TRAP at concentrations of 2.5 mM and higher, while TBA-RS measurement, GSH-Px, CAT and SOD activities were not affected. Furthermore, l-beta-imidazolelactic acid provoked antioxidant effects at high concentrations (5-10 mM) as observed by the reduction of chemiluminescence, although this compound enhanced chemiluminescence at low concentrations (0.5-1 mM). These results suggest that in vitro oxidative stress is elicited by histidine but only at supraphysiological concentrations.
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PMID:Effects of histidine and imidazolelactic acid on various parameters of the oxidative stress in cerebral cortex of young rats. 1503 81

Down syndrome (DS) is the congenital birth defect responsible for the greatest number of individuals with mental retardation. It arises due to trisomy of human chromosome 21 (HSA21) or part thereof. To date there have been limited studies of HSA21 gene expression in trisomy 21 conceptuses. In this study we investigate the expression of the HSA21 antioxidant gene, Cu/Zn-superoxide dismutase-1 (SOD1) in various organs of control and DS aborted conceptuses. We show that SOD1 mRNA levels are elevated in DS brain, lung, heart and thymus. DS livers show decreased SOD1 mRNA expression compared with controls. Since non-HSA21 antioxidant genes are reported to be concomitantly upregulated in certain DS tissues, we examined the expression of glutathione peroxidase-1 (GPX1) in control and DS fetal organs. Interestingly, GPX1 expression was unchanged in the majority of DS organs and decreased in DS livers. We examined the SOD1 to GPX1 mRNA ratio in individual organs, as both enzymes form part of the body's defense against oxidative stress, and because a disproportionate increase of SOD1 to GPX1 results in noxious hydroxyl radical damage. All organs investigated show an approximately 2-fold increase in the SOD1 to GPX1 mRNA ratio. We propose that it is the altered antioxidant ratio that contributes to certain aspects of the DS phenotype.
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PMID:An altered antioxidant balance occurs in Down syndrome fetal organs: implications for the "gene dosage effect" hypothesis. 1506 40

Phenylketonuria (PKU) is an autossomal recessive disease caused by phenylalanine-4-hydroxylase deficiency, which is a liver-specific enzyme that catalyzes the hydroxylation of l-phenylalanine (Phe) to l-tyrosine (Tyr). The deficiency of this enzyme leads to the accumulation of Phe in the tissues and plasma of patients. The clinical characterization of this disease is mental retardation and other neurological features. The mechanisms of brain damage are poorly understood. Oxidative stress is observed in some inborn errors of intermediary metabolism owing to the accumulation of toxic metabolites leading to excessive free radical production and may be a result of restricted diets on the antioxidant status. In the present study we evaluated various oxidative stress parameters, namely thiobarbituric acid-reactive species (TBA-RS) and total antioxidant reactivity (TAR) in the plasma of PKU patients. The activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were also measured in erythrocytes from these patients. It was observed that phenylketonuric patients present a significant increase of plasma TBA-RS measurement, indicating a stimulation of lipoperoxidation, as well as a decrease of plasma TAR, reflecting a deficient capacity to rapidly handle an increase of reactive species. The results also showed a decrease of erythrocyte GSH-Px activity. Therefore, it is presumed that oxidative stress is involved in the pathophysiology of the tissue damage found in PKU.
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PMID:Oxidative stress in patients with phenylketonuria. 1587 43


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