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)

Pregnant Long-Evans rats were given a single i.p. injection of 30 mg/kg of methylazoxymethanol (MAM) acetate or saline on day 14 of gestation (vaginal plug = day 0). All litters were reduced to 8 at birth and were reared by their biological dams. Between 49-192 days of age all offspring were examined on open-field, figure-8 (at two different ages), and hole-board tests of activity, as well as passive avoidance and Biel water maze tests of learning (also at two different ages). The MAM offspring showed no increase in mortality, but weighed less than controls, a difference that remained relatively constant throughout the experiment. At 204-215 days of age the MAM offspring were confirmed to be micrencephalic, a known effect of this drug at this dose and exposure period. On all tests of activity the MAM offspring were markedly hyperactive. The female progeny also exhibited a pronounced impairment of normal activity habituation patterns. The MAM males, however, showed a marked impairment of passive avoidance performance, while the females did not. At 2 months of age the MAM offspring also showed a pronounced deficit in learning a water maze. This maze deficit had not abated when tested again at 6 months of age. The MAM induced brain and behavioral abnormalities provide a potentially useful animal model of congenital micrencephaly and associated mental retardation.
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PMID:Pervasive hyperactivity and long-term learning impairments in rats with induced micrencephaly from prenatal exposure to methylazoxymethanol. 654 Jun 18

A minority of individuals with mental retardation engage in offensive sexual behavior (e.g., child molestation, genital exposure, rape). Many of these individuals may benefit from the adjunctive administration of antilibidinal drugs. The two most widely used are the antiandrogens, medroxyprogesterone acetate (MPA) and cyproterone acetate (CPA). In the present paper the efficacy, cautions, side effects, and mode(s) of action of these substances were reviewed and medico-legal issues surrounding their use discussed. Controlled studies of antilibidinal agents with adequate numbers of patients using clearly defined (e.g., cognitive abilities) and valid and reliable outcome measures are needed.
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PMID:Review of the role of two antilibidinal drugs in the treatment of sex offenders with mental retardation. 770 38

Mental retardation, hydrocephalus, and agenesis of the corpus callosum are observed both in fetal alcohol syndrome (FAS) and in children with mutations in the gene for the cell adhesion molecule L1. We studied the effects of ethanol on cell-cell adhesion in mouse fibroblasts transfected with human L1. L1-transfected fibroblasts exhibited increased cell-cell adhesion compared with wild-type or vector-transfected controls. Ethanol potently and completely inhibited L1-mediated adhesion both in transfected L cells and NIH/3T3 cells. Half-maximal inhibition was observed at 7 mM ethanol, a concentration achieved in blood and brain after ingesting one alcoholic beverage. In contrast, ethanol did not inhibit the adhesion of fibroblasts transfected with vector alone or with N-CAM-140. L1-mediated cell-cell adhesion was inhibited with increasing potency by n-propanol and n-butanol, but was not inhibited at all by n-alcohols of 5 to 8 carbons, acetaldehyde, or acetate, suggesting that ethanol interacts directly with a small hydrophobic pocket within L1. Phenylalanine, teratogenic anticonvulsants, and high concentrations of glucose did not inhibit L1-mediated cell-cell adhesion. Ethanol also inhibited potently the heterotypic adhesion of rat cerebellar granule cells to a monolayer of L1-transfected NIH/3T3 cells, but had no effect on their adhesion to N-CAM-140 or vector-transfected NIH/3T3 cells. Because L1 plays a role in both neural development and learning, ethanol inhibition of L1-mediated cell-cell interactions could contribute to FAS and ethanol-associated memory disorders.
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PMID:Alcohol inhibits cell-cell adhesion mediated by human L1. 860 70

The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked multisystem disorder with major abnormalities of eyes, nervous system, and kidneys. Clinical manifestations include congenital cataract, mental retardation, and renal tubular dysfunction. A gene (OCRL1) responsible for OCRL was identified by positional cloning and its product OCRL-1 protein was shown to be a phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] 5-phosphatase localized to the Golgi apparatus. We describe three mutations in OCRL1, one in a patient with severe phenotype and two in patients with moderate phenotype (degree of mental retardation and musculoskeletal abnormalities). The patient with severe phenotype had a G-to-A transition at nucleotide (nt) 1,739, causing an Arg-to-Gln substitution at amino acid 577, and one patient with moderate phenotype had a C-to-G transversion at nt 1,812, leading to a His-to-Gln substitution at amino acid 601. Both Arg-577 and His-601 are encoded by exon 15 and are probably important for proper function of this protein, since these are conserved in various enzymes catalyzing dephosphorylation of inositol compounds. In the other patient with the moderate phenotype, there was a G-to-A transition at nt 2,797 located at the 3'-end of exon 22. This substitution led to a skip of the same exon as well as conversion of codon-930 from GCT (Ala) to ACT (Thr) in the normal-size transcript. When we measured the enzyme activity in skin fibroblasts from the three patients, the activity was less than 10%, compared to findings in normal controls. Western blot analysis showed absence or severe decrease in OCRL-1 protein in cell lysates derived from these patients.
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PMID:Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes. 963 63

We report on the successful treatment of a case of infantile subdural fluid collection after cardiac surgery by administration of methylprednisolone acetate into the subdural cavity. The protein content in subdural fluid did not change even after administration of this steroid and was not a good indicator of the efficacy of treatment; however, the content of platelet-activating factor (PAF), an inflammatory mediator, in the fluid removed from the subdural cavity decreased rapidly after administration of the steroid. Subdural fluid collection subsequently decreased and mental retardation was improved. Our findings suggest that PAF content is a good indicator of the severity of infantile subdural fluid collection.
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PMID:Administration of methylprednisolone acetate into the subdural cavity in an infant with subdural fluid collection. PAF is a good indicator of the efficacy of the treatment. 975 99

Cortical malformations resulting from aberrant brain development can be associated with mental retardation, dyslexia, and intractable forms of epilepsy. Despite emerging interest in the pathology and etiology of cortical malformations, little is known about the phenotype of cells within these lesions. In utero exposure to the DNA methylating agent methylazoxymethanol acetate (MAM) during a critical stage in neurodevelopment results in animals with distinct clusters of displaced neurons in hippocampus, i.e. nodular heterotopia. Here we examined the molecular and electrophysiological properties of cells within hippocampal heterotopia using rats exposed to MAM during gestation. Molecular analysis revealed that heterotopic cells do not express mRNA markers normally found in hippocampal pyramidal cells or dentate granule cells (SCIP, Math-2, Prox-1, neuropilin-2). In contrast, Id-2 mRNA, normally abundant in Layer II-III supragranular neocortical neurons but not in CA1 pyramidal neurons, was prominently expressed in hippocampal heterotopia. Current-clamp analysis of the firing properties of heterotopic neurons revealed a striking similarity with supragranular cortical neurons. In particular, both cells were characterized by small hyperpolarizing 'sag' potentials, high input resistance values, slow spike-train afterhyperpolarizations, and the absence of a depolarizing afterpotential. Normotopic CA1 pyramidal neurons (e.g. pyramidal cells with normal lamination adjacent to a heterotopia) in the MAM brain exhibited molecular and electrophysiological properties that were nearly identical to those of age-matched CA1 pyramidal neurons from control rats. We conclude that neuronal heterotopiae in the hippocampus of MAM-exposed rats are comprised of neurons with a Layer II-III supragranular cortex phenotype. The MAM model, therefore, may serve as a useful tool in examination of the factors influencing aberrant brain development and epilepsy.
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PMID:Hippocampal heterotopia with molecular and electrophysiological properties of neocortical neurons. 1237 51

Hyperammonemia is a common finding in children with methylmalonic acidemia, an inherited metabolic disease characterized by mental retardation, convulsions, and accumulation of methylmalonic acid (MMA). Although it has been suggested that MMA induces convulsions through succinate dehydrogenase (SDH) inhibition, very little is known about the contribution of hyperammonemia to the development of convulsions in these patients. In the present study we investigated the effects of ammonium ions on the convulsant action of MMA, MMA-induced inhibition of striatal succinate dehydrogenase, and the striatal content of thiobarbituric acid-reactive substances (TBARS). Adult rats were injected with ammonium acetate (1.5 mmol/kg, sc) or sodium acetate (1.5 mmol/kg, sc), followed 5 min later by buffered MMA (3 micromol/microl) or NaCl (4.5 micromol/microl) injected into the striatum. The animals were observed in an open field for the appearance of convulsive episodes. After 30 min of behavioral evaluation, the animals were sacrificed and had their striatal TBARS content measured. Ammonium acetate pretreatment caused no behavioral effects per se, but potentiated MMA-induced convulsions and increased basal TBARS content and MMA-induced TBARS production in the striatum. Ammonium chloride had no effect on basal succinate dehydrogenase activity and did not alter MMA-induced inhibition of SDH in vitro. These results suggest that ammonia potentiates MMA-induced behavioral effects through a mechanism that does not involve further succinate dehydrogenase inhibition, but may involve facilitation of MMA-induced oxidative damage and provide evidence that ammonia and MMA may have mutually additive toxicity.
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PMID:Ammonia potentiates methylmalonic acid-induced convulsions and TBARS production. 1289 56

Arginase deficiency is an urea cycle disorder that generally presents with mental retardation and spasticity, yet uncommonly with episodes of hyperammonemia. A female adolescent with arginase deficiency developed hyperammonemic episodes temporally related to her menstrual cycle, which ceased upon adequate treatment with depot medroxy progesterone acetate. A similar case was previously reported. A catamenial trigger should be considered in adolescent female arginase-deficient patients with episodes of hyperammonemia.
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PMID:A patient with arginase deficiency and episodic hyperammonemia successfully treated with menses cessation. 1696

Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of guanidinoacetate (GAA) and depletion of creatine. Affected patients present epilepsy and mental retardation whose etiopathogeny is unclear. In a previous study we showed that instrastriatal administration of GAA caused a reduction of Na(+),K(+)-ATPase and creatine kinase (CK) activities, as well as an increase in TBARS (an index of lipid peroxidation). In the present study we investigated the in vitro and in vivo effects of GAA on glucose uptake from [U-(14)C] acetate (citric acid cycle activity) and on the activities of complexes II, II-III, III and IV of the respiratory chain in striatum of rats. Results showed that 50 and 100 microM GAA (in vitro studies) and GAA administration (in vivo studies) significantly inhibited complexes II and II-III, respectively, but did not alter complexes III and IV, as well as CO(2) production. We also studied the influence of taurine or vitamins E and C on the inhibitory effects caused by intrastriatal administration of GAA on complexes II and II-III, Na(+),K(+)-ATPase and CK activities, and on TBARS in rat striatum. Pre-treatment with taurine and vitamins E and C revealed that taurine prevents the effects of intrastriatal administration of GAA on the inhibition of complex II, complex II-III, and Na(+),K(+)-ATPase activities. Vitamins E and C prevent the effects of intrastriatal administration of GAA on the inhibition of CK and Na(+),K(+)-ATPase activities, and on the increase of TBARS. The data suggest that GAA in vivo and in vitro treatment disturbs important parameters of striatum energy metabolism and that oxidative damage may be mediating these effects. It is presumed that defects in striatum bioenergetics might be involved in the pathophysiology of striatum damage characteristic of patients with GAMT-deficiency.
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PMID:Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. 1740 7

Hippocampal excitability and the metabolic glial-neuronal interactions were investigated in 22-week-old mice with motor neuron degeneration (mnd), a model of progressive epilepsy with mental retardation. Mnd mice developed spontaneous spikes in the hippocampus and were more susceptible to kainate-induced seizures compared with control mice. Neuronal hyperexcitability in their hippocampus was confirmed by the selective increase of c-Fos positive nuclei. Glial activation and pro-inflammatory cytokines over-expression were observed in the hippocampus of mnd mice, even in the absence of marked hippocampal neurodegeneration, as suggested by unchanged amounts of neuroactive amino acids and N-acetyl aspartate. Concentration of other amino acids, including GABA and glutamate, was not changed as well. However, ex vivo(13) C magnetic resonance spectroscopy, after simultaneous injection of [1-(13) C]glucose and [1,2-(13) C]acetate, followed by decapitation, showed decreased [1,2-(13) C]GABA formation from hippocampal astrocytic precursors and a marked reduction in [4,5-(13) C]glutamate derived from glutamine. We suggest that astrocyte dysfunction plays a primary role in the pathology and that mnd mice are of value to investigate early pathogenetic mechanism of progressive epilepsy with mental retardation.
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PMID:Neuronal hyperexcitability and seizures are associated with changes in glial-neuronal interactions in the hippocampus of a mouse model of epilepsy with mental retardation. 2104 73


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