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

A case of tuberous sclerosis with congenital brain tumor was reported. The diagnosis was made on the basis of the pathological findings of subependymal giant cell astrocytoma, after surgery at the newborn period. After the neonatal period, the patient presented the classical triad of seizures, white spot of skin and mental retardation. The exact nature of tumor-forming giant cells remains controversial. We studied the nature of these cells using immunohistochemical method. GFAP, S-100 protein and NSE stains were all positive. This result suggested that the tumor cells had the features of both neurons and astrocytes.
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PMID:[A case of tuberous sclerosis with congenital brain tumor; an immunohistochemical study]. 159 Oct 26

The brain of a child with Down syndrome develops differently from a normal one, attaining a form reduced in size and altered in configuration. Directly related to the mental retardation are neuronal modifications manifest as alterations of cortical lamination, reduced dendritic ramifications, and diminished synaptic formation. However, selected cholinergic marker enzymes such as choline acetyl transferase and acetyl cholinesterase have shown no alterations in young children with Down syndrome. The pace of the neuronal transformations is related to stage of maturation. With early growth and development, the normal dendritic tree continuously expands. In Down syndrome, at 4 months of age, the neurons show a relatively expanded dendritic tree, but during the first year the dendrites stop growing and become atrophic relative to control neurons. Accompanying these neuronal irregularities are subtle alterations of other cell types: astrocyte, oligodendrogliocyte, microglia, and endothelial cell. In early infancy, one of the astrocytic markers, GFAP, is not altered, but there is greater expression of S-100 protein in the temporal lobe in Down syndrome. Oligodendrogliocyte dysfunction is reflected in delayed myelination in pathways of frontal and temporal lobes. Microglia appear more prominent in Down syndrome. A minority of children with Down syndrome have vascular dysplasias and focal calcification of basal ganglia. In young children, expression of beta-amyloid in Down syndrome is no different than in normal children but disappears after age two, only to reappear in adults. As some of these studies suggest, the identification of genes on chromosome 21 and the determination of the gene product allow the production of specific antibodies and, through immunohistochemical techniques, the identification of the expression of these proteins in both normal development and Down syndrome. Specifically, the localization and appearance in development of proteins such as the beta-subunit of S-100, beta-amyloid (A4 protein), superoxide dismutase, and OK-2 are providing the means for better understanding the morphogenesis of the cellular and eventually molecular basis for the mental retardation in Down syndrome.
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PMID:Growth and development of the brain in Down syndrome. 183 82

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

Alexander's disease is a progressive degenerative neurological disorder developing in early childhood which is characterized by accumulation of Rosenthal fibres throughout the cerebral white matter. These fibres are composed of glial fibrillary acidic protein and ubiquinated alpha beta crystallin. The absence of atypia, increased cellularity, mitotic activity or necrosis in biopsy material allows differentiation from neoplasia glial processes. Clinical features suggestive of the diagnosis include progressive mental retardation with an increase in head circumference.
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PMID:Test and teach. Number seventy-three. Diagnosis: Alexander's disease. 826 44

Medulloblastoma is the most common primitive neuroectodermal tumor (PNET) of the central nervous system. Standard whole neuroaxis radiation prolongs survival, but causes mental retardation and growth disturbance. It is important to find appropriate prognostic indicators for medulloblastoma in children. We assessed the prognostic values of N-myc expression in medulloblastoma. Nineteen medulloblastoma or supratentorial PNET (SPNET) patients (15 males and 4 females) were immunohistochemically investigated for N-myc expression. Sixteen patients were N-myc-positive, and three were N-myc-negative. N-myc-positive patients had a tendency towards a poor outcome (P = 0.1125). N-myc-negative tumors were more differentiated towards glial lineage than N-myc-positive tumors. N-myc-negative and GFAP-positive patients (n = 2) tended to survive N-myc-positive and GFAP-negative patients (n = 13). In medulloblastoma and SPNET patients, N-myc expression may become an appropriate indicator of poor prognosis and primitive cell differentiation.
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PMID:An immunohistochemical analysis of medulloblastoma and PNET with emphasis on N-myc protein expression. 891 71

Three cases of subependymal giant cell astrocytoma (SEGA) in the women aged 23, 26, and 36 years were reported. Two of them had no clinical evidence of tuberous sclerosis complex (TSC) and the one woman presented apparent mental retardation. All patients manifested sudden clinical onset with symptoms of elevated intracranial pressure due to tumor of lateral ventricles and obstructive hydrocephalus. At surgery, the neoplasm was removed totally in one case and resected partially in 2 cases. Histologically, the tumors were composed of large polygonal cells with vesicular nuclei, prominent nucleoli and glassy eosinophilic cytoplasm, intermingled with spindle and small cells. In addition, multinucleated and bizarre giant cells were present, but they were very numerous in one case only. The tumor cells revealed in all cases variegated immunoreactivity for glial fibrillary acidic protein (GFAP), S-100 protein, vimentin (VIM) and neuron-specific enolase (NSE), with stronger expression of VIM than GFAP in 2 cases. Immunostaining of neurofilament proteins and synaptophysin was negative. The results suggest rather astroglial incomplete or aberrant differentiation and maturation than neuronal differentiation of tumor cells. The immunohistochemical variations of SEGA in asymptomatic TSC cases and those associated with tuberous sclerosis are discussed.
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PMID:Subependymal giant cell astrocytoma: clinical, histologic and immunohistochemical characteristic of 3 cases. 959 53

Glial cells and their interactions with neurons play vital roles during the ontogeny of the nervous system and in the adult brain. Alcohol intake during pregnancy can cause mental retardation and neurobehavioral disorders as well as fetal alcohol syndrome (FAS). Clinical and experimental evidence indicate that in utero alcohol exposure induces structural and functional abnormalities in gliogenesis and in glial-neuronal interactions, suggesting a potential role of glial cells on ethanol-induced developmental brain abnormalities. In vivo studies have shown ethanol-associated alterations in the migration of neurons and radial glial as well as in astrogliogenesis and myelin development. In astrocytes in primary culture, ethanol has been found to (1) impair cell growth and differentiation, (2) decrease the levels of glialfibrillary acidic protein or GFAP (an astrocyte marker) and its gene expression and (3) interfere with the stimulatory effect of trophic factors affecting their release and receptor expression. Evidence also suggests that ethanol affects intracellular protein trafficking, which may mediate some effects of ethanol on astroglial cells. These findings suggest that glial cells are target of ethanol toxicity during brain development and may underlie the neurodevelopmental abnormalities observed after in utero alcohol exposure and in FAS.
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PMID:Glia and fetal alcohol syndrome. 1177 Aug 80

In recent years, improvement in diagnostic techniques has led to better recognition of "disorders of cortical development". These disorders constitute a significant cause of epilepsy, mental retardation, developmental delay and neurological deficits in childhood, and may also contribute to the pathogenesis of psychological and neurodegenerative diseases in adults. Hitherto, however, few systematic studies of the human fetal cortex have been performed, and little is known about the ontogenetic processes of the neocortex in man. The aim of the study is to establish an understanding of the developmental events that occur in the second and third trimesters of gestation, by investigating the biochemical patterns of development of the human neocortex during this period. The temporal and spatial patterns of expression of the neuronal markers gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), dopamine beta hydroxylase (DBH), dopamine receptor DR1 and synaptophysin, as well as the glial cell markers glial fibrillary acidic protein (GFAP), S100B and excitatory amino acid transporter protein GLT-1 are delineated in the fetal cortex using immunohistochemistry. Results of this study showed that different neuronal and glial cell proteins follow different developmental patterns and many show inter- or intra-regional variations in expression. Details of these patterns are described and discussed. The early expression of these proteins suggests that they play important roles in the developmental processes of cell proliferation, migration and differentiation. Both neurotransmitters and glial cell proteins probably function outside the confines of synapses in the fetal brain, as paracrine/autocrine factors. Early developmental events seem to be dictated by an innate programme, whereas late events may be more susceptible to extrinsic influences. It is hoped that knowledge of the normal developmental process can lead to better understanding of the causes and mechanisms of "disorders of cortical development", and to better treatments.
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PMID:Development of the human cerebral cortex: a histochemical study. 1259 27

Individuals with tuberous sclerosis complex (TSC) exhibit a variety of neurologic abnormalities, including mental retardation, epilepsy, and autism. Examination of human TSC brains demonstrate dysplastic astrocytes and neurons, areas of abnormal neuronal migration (tubers), and hamartomatous growths, termed subependymal nodules, which can progress to subependymal giant cell astrocytomas (SEGA). Previous studies have suggested that these neuropathologic features may result from abnormal neuroglial cell differentiation. In an effort to provide support for this hypothesis and to identify specific markers of aberrant neuroglial cell differentiation in TSC, we employed gene expression profiling on Tsc1 conditional knockout (Tsc1(GFAP)CKO) mouse astrocytes. We identified several transcripts implicated in central nervous system development that are differentially expressed in Tsc1(-/-) astrocytes compared to wild-type astrocytes. We validated the differential expression of select transcripts on the protein level both in primary cultures of Tsc1(-/-) astrocytes and in Tsc1(GFAP)CKO mouse brains. Moreover, we show that these markers are also differentially expressed within cortical tubers, but not in adjacent normal tissue from TSC patient brains. This study provides supportive evidence for a developmental defect in neuroglial cell differentiation relevant to the genesis of TSC nervous system pathology and underscores the utility of mouse modeling for understanding the molecular pathogenesis of human disease.
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PMID:Expression profiling in tuberous sclerosis complex (TSC) knockout mouse astrocytes to characterize human TSC brain pathology. 1499 11

Fragile X syndrome, a common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP) due to a mutation in the FMR1 gene. We investigated the differentiation of neural stem cells generated from the brains of fmr1-knockout (KO) mice and from postmortem tissue of a fragile X fetus. Mouse and human FMRP-deficient neurospheres generated more TuJ1-positive cells (3-fold and 5-fold, respectively) than the control neurospheres generated from normal mouse and human brains, and these cells showed morphological alterations with fewer and shorter neurites and a smaller cell body volume. The number of cells expressing glial fibrillary acidic protein and generated by these neurospheres was reduced because of increased apoptotic cell death. Furthermore, there was an increase in a population of cells with intense oscillatory Ca2+ responses to neurotransmitters in differentiated cells lacking FMRP. In addition, the number of cells in a cohort of bromodeoxyuridine-labeled newborn cells was increased in the subventricular zone of the telencephalon of the fmr1-KO mouse in vivo. These results demonstrate substantial alterations in the early maturation of FMRP-deficient neural stem cells in fragile X syndrome and in the fmr1-KO mice.
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PMID:Altered differentiation of neural stem cells in fragile X syndrome. 1631 62


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