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

Down's syndrome (DS) is a genetic disorder involving an excess of chromosome 21 (trisomy 21) in approximately 96% of the cases and comprises approximately 15% of the population with mental retardation (Heller, 1969). In addition to the constitutional mental deficiencies associated with the syndrome many DS patients develop dementia associated with Alzheimer's disease (AD) in their later years of life (Thase et al., 1984). The genetic locus for Cu,Zn-superoxide dismutase (SOD1), a key enzyme in free radical metabolism, is located on chromosome 21, and the activity level of this enzyme is elevated by approximately 50% in a variety of cells of DS patients (see Kedziora and Bartosz, 1988; Sinet, 1982). Because alterations in free radical metabolism may be involved in neuronal death and may be associated with a number of pathological manifestations of DS, it is important to understand the role of free radical metabolism in cognitive impairments of DS, the topic discussed in this chapter.
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PMID:The role of alterations in free radical metabolism in mediating cognitive impairments in Down's syndrome. 145 May 86

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

Recent evidence suggests that Alzheimer's disease is an etiologically heterogeneous disorder. A human model of Alzheimer's disease exists that avoids such problems of etiologic heterogeneity. Down syndrome (DS), trisomy 21, is a genetic disorder in which an extra portion of chromosome 21 leads to mental retardation, short stature, and phenotypic abnormalities. Prior investigations by others have shown that DS subjects over 40 years of age demonstrate neuropathologic and neurochemical defects postmortem that are virtually indistinguishable from those found in brains of Alzheimer's disease patients and a universal cognitive deterioration more severe in demented than nondemented older DS subjects. In our study, these nondemented older DS subjects show a distinctive pattern of age-related deficits, while a more global pattern is seen in demented older DS subjects. Dementia occurs in 40% of older DS subjects. We find that in older demented DS subjects positron emission tomography (PET) shows identical patterns of abnormal glucose metabolism as those described previously in Alzheimer's disease patients, selectively involving the phylogenetically newer association areas of parietal and temporal neocortices but sparing primary sensory and motor regions. Further, we find in older demented DS patients quantitative computer-assisted tomography (CT) indicates accelerated neuronal loss and brain atrophy, similar to that previously shown in Alzheimer's disease patients. As a potential use of the DS model, we observed a case of DS with dementia but without mental retardation. This case suggests that expression of dementia in DS may involve genes on chromosome 21 other than in the "obligatory" distal segment of the q arm. Alternatively, differential expression of genes on the q arm of chromosome 21 might cause dementia without phenotypic features and mental retardation.
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PMID:Nature of mental retardation and dementia in Down syndrome: study with PET, CT, and neuropsychology. 149 38

Down syndrome (DS) is a major cause of congenital heart and gut disease and mental retardation. DS individuals also have characteristic facies, hands, and dermatoglyphics, in addition to abnormalities of the immune system, an increased risk of leukemia, and an Alzheimer-like dementia. Although their molecular basis is unknown, recent work on patients with DS and partial duplications of chromosome 21 has suggested small chromosomal regions located in band q22 that are likely to contain the genes for some of these features. We now extend these analyses to define molecular markers for the congenital heart disease, the duodenal stenosis, and an "overlap" region for the facial and some of the skeletal features. We report the clinical, cytogenetic, and molecular analysis of two patients. The first is DUP21JS, who carries both a partial duplication of chromosome 21, including the region 21q21.1-q22.13, or proximal q22.2, and DS features including duodenal stenosis. Using quantitative Southern blot dosage analysis and 15 DNA sequences unique to chromosome 21, we have defined the molecular extent of the duplication. This includes the region defined by DNA sequences for APP (amyloid precursor protein), SOD1 (CuZn superoxide dismutase), D21S47, SF57, D21S17, D21S55, D21S3, and D21S15 and excludes the regions defined by DNA sequences for D21S16, D21S46, D21S1, D21S19, BCE I (breast cancer estrogen-inducible gene), D21S39, and D21S44. Using similar techniques, we have also defined the region duplicated in the second case occurring in a family carrying a translocation associated with DS and congenital heart disease. This region includes DNA sequences for D21S55 and D21S3 and excludes DNA sequences for D21S47 and D21S17.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Down syndrome: molecular mapping of the congenital heart disease and duodenal stenosis. 153 Nov 66

Current research indicates the importance of synaptic number and structure in plastic processes such as development, learning and memory, and aging. As such, the examination of these neural features has become an important factor in research on human conditions such as mental retardation, aging and Alzheimer's disease. Synaptic research in human tissue typically involves delayed post-mortem fixation, therefore the current research was designed to examine the effect of post-mortem delay on synaptic number and structure in tissue stained with either routine osmium lead citrate/uranyl acetate (osmium) or ethanol phosphotungstic acid (EPTA). Results indicate that synaptic density shows either a gradual decline (EPTA) or an initial marked drop followed by a plateau (osmium) up to 10-15 h post-mortem depending on the stain used. The number of synaptic vesicles per synapse also undergoes a gradual decline. Measures of synaptic structure were more stable, with the primary change being an initial increase in the cross-sectional length of the synapse. Maximal height of the pre- and postsynaptic dense elements were not affected by post-mortem delay. The EPTA stain gave the best estimates of synaptic parameters with short post-mortem delays. These results indicate that different synaptic measures (and stains) show different responses to post-mortem fixation delay, and that experimental or statistical methods must be used to control for post-mortem effects.
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PMID:Quantifying synaptic number and structure: effects of stain and post-mortem delay. 169 64

The characteristic features of the brain cortex architectonics were studied and compared in Alzheimer's disease, oligophrenia and Down's disease. Some analogous alterations were established to be characteristic of all the three forms of pathology. On this basis the role is discussed of congenital disturbances of the angioarchitectonics in both mental retardation and dementia development.
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PMID:[Pathological structure of blood vessels of cerebral cortex in Alzheimer's disease in comparison with various other types of mental retardation (oligophrenia, Down's syndrome)]. 170 71

Neurological manifestations of xeroderma pigmentosum, a rare autosomal recessive neurocutaneous syndrome, are variable. The association with progressive mental retardation, usually with onset in childhood, is well known. We present a case of x.p. with progressive presenile dementia. This combination has, to our knowledge, not yet been reported in the literature. Although no hints on another aetiology have been found, the coincidental combination of x.p. with M. Alzheimer has to be taken into consideration. CT scan and MRI showed a marked cerebral atrophy.
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PMID:[Presenile dementia in xeroderma pigmentosum]. 174 55

Based on recent studies of neuroimmune networks, the lymphocyte binding of serotonin neurotransmitter was studied in patients with Alzheimer's disease, idiopathic mental retardation, and autism. The specific binding to lymphocytes of [3H]serotonin, at a single concentration of 100 nM, was significantly reduced in Alzheimer's disease patients as compared to aged controls (group mean of 3.667 +/- 2.301 v 7.506 +/- 1.717 picomoles; p = 0.001), and in children with idiopathic mental retardation as compared to healthy children (group mean of 3.694 +/- 1.627 v 5.792 +/- 1.902 picomoles; p = 0.003). However, autistic children did not differ significantly from the healthy children (group mean of 5.287 +/- 1.987 v 5.792 +/- 1.902 picomoles; p = 0.475). Reduced lymphocyte binding of serotonin may be an indication of breakdown of an unknown neuroimmune pathway relevant to the pathophysiology of Alzheimer's disease and idiopathic mental retardation.
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PMID:Binding of [3H]serotonin to lymphocytes in patients with neuropsychiatric disorders. 209 81

In trisomy 21, pathogenesis of mental retardation is still poorly understood although the knowledge of the genic content of chromosome 21 is steadily increasing. Short of discovering how to silence selectively one of the 3 chromosomes 21, no rational medication can be envisaged before pathogenesis has been unraveled, at least partially. A biochemical scheme of impairment of mental efficiency is presented. Secondarily, the possible deleterious effects of a given gene overdose are discussed. Cu/Zn SOD, cystathionine beta synthase, S 100 beta protein, phosphofructokinase, purine synthesis and adenosine pharmacology, thyroid disturbance, and elevated TSH with low rT3 as well as biopterine metabolism interferences are reviewed. It is observed that the metabolic paths controlled by these genes, although unrelated at first glance, are in fact tightly related by their effects, just as if synteny was in some way related to biochemical cooperation or mutually controlled regulation. Experiments in vitro have demonstrated a peculiar sensitivity of trisomic 21 lymphocytes to methotrexate. From this starting point, systematic research of special sensitivities has begun. Clinical observations and relevant statistical methods allow study of the speed of mental development under various medications. The interest of regulating thyroid metabolism, when needed, is exemplified. Reequilibration of monocarbon metabolism is discussed and the seemingly favourable effect of folinic acid medication in pseudo-Alzheimer complication is presented.
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PMID:Pathogenesis of mental deficiency in trisomy 21. 214 47

Review of the clinical cytogenetic literature provides compelling evidence for a specific relationship between imbalance of particular chromosomes or chromosomal regions and the appearance of defined patterns of phenotypic abnormalities. In many instances, detailed phenotypic mapping has made it possible to assign portions of a phenotype to relatively small chromosome segments, which are sometimes referred to as "critical regions." However, since these regions are usually defined by a subset of the phenotypic manifestations of an aneuploidy syndrome--generally those anomalies that are regarded as most characteristic or readily observable--it is important not to fall into the trap of thinking that it is imbalance of only these regions that has deleterious effects on development and function. Thus, in Down syndrome, the presence of an extra copy of the proximal part of 21q22.3 appears to result in the typical physical phenotype--as defined principally in terms of the characteristic facial and hand anomalies and congenital heart defect--in addition to mental retardation. But, duplication of proximal 21q also affects mental development, and the regions responsible for many other aspects of the Down syndrome phenotype, including Alzheimer disease, have not been defined at all. Therefore, it remains likely that loci present on many parts of the long arm of chromosome 21 play a role in the development of the overall phenotype of Down syndrome. The immediate effect at the molecular level of an aneuploidy-caused alteration in gene dose appears to be a non-compensated commensurate change in the production of gene products.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The consequences of chromosome imbalance. 214 68


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