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)

Albright hereditary osteodystrophy (AHO), also known as Martin-Albright syndrome (MAS), is a rare autosomal dominantly transmitted disease characterized by short stature, obesity, mental retardation, a round facies, and brachymetacarpia and -tarsia, as well as cutaneous calcification. The disease is caused by mutations in the GNAS gene localized on chromosome 20q13.2 encoding for an adenyl-cyclase-stimulating protein (Gsalpha). A 58-year-old patient presented with small stature since childhood, moderate mental retardation, round facies and soft tissue masses on the thighs. A biopsy of the latter showed subcutaneous ossification. Laboratory results showed hypocalcemia, as well as increased plasma levels of PTH and calcitonin. The clinical diagnosis was confirmed by detection of reduced activity of Gsalpha. In patients with cutaneous calcification and disturbed calcium metabolism, AHO is an important differential diagnostic consideration.
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PMID:First diagnosis of Martin-Albright syndrome in a 58-year-old patient. 1913 95

In human patients, cortical dysplasia produced by Doublecortin (DCX) mutations lead to mental retardation and intractable infantile epilepsies, but the underlying mechanisms are not known. DCX(-/-) mice have been generated to investigate this issue. However, they display no neocortical abnormality, lessening their impact on the field. In contrast, in utero knockdown of DCX RNA produces a morphologically relevant cortical band heterotopia in rodents. On this preparation we have now compared the neuronal and network properties of ectopic, overlying, and control neurons in an effort to identify how ectopic neurons generate adverse patterns that will impact cortical activity. We combined dynamic calcium imaging and anatomical and electrophysiological techniques and report now that DCX(-/-)EGFP(+)-labeled ectopic neurons that fail to migrate develop extensive axonal subcortical projections and retain immature properties, and most of them display a delayed maturation of GABA-mediated signaling. Cortical neurons overlying the heterotopia, in contrast, exhibit a massive increase of ongoing glutamatergic synaptic currents reflecting a strong reactive plasticity. Neurons in both experimental fields are more frequently coactive in coherent synchronized oscillations than control cortical neurons. In addition, both fields displayed network-driven oscillations during evoked epileptiform burst. These results show that migration disorders produce major alterations not only in neurons that fail to migrate but also in their programmed target areas. We suggest that this duality play a major role in cortical dysfunction of DCX brains.
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PMID:Abnormal network activity in a targeted genetic model of human double cortex. 1914 32

Down syndrome has a prevalence of one in 500 to one in 1,000 live births and is the most common cause of mental retardation. Most patients are treated in childhood and adolescence for mental or growth retardation. Studies that evaluate bone mass in Down syndrome are limited, and many are small case series in pediatric and adult populations who live either in the community or in residential institutions. Several environmental and hormonal factors contribute to low bone mineral density in such patients. Muscle hypotonia, low amounts of physical activity, poor calcium and vitamin D intakes, hypogonadism, growth retardation and thyroid dysfunction contribute to substantial impairments in skeletal maturation and bone-mass accrual that predispose these patients to fragility fractures. Here, we review indications and limitations of bone-mass measurements in children, summarize the endocrine and skeletal abnormalities in patients presenting with Down syndrome, and review studies that investigate therapeutic strategies for such patients.
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PMID:Endocrine and musculoskeletal abnormalities in patients with Down syndrome. 1942 Dec 41

It has been suggested that overexpression of neuronal Ca2+ sensor-1 (NCS-1) protein is implicated in the pathophysiology of neurodisorders such as schizophrenia, bipolar disturbance and X-linked mental retardation. The mechanism by which NCS-1 would be involved in the causes and/or consequences of these neurodisorders is still far from elucidation. Independent evidence has pointed NCS-1 as a key regulator of synaptic efficacy by altering the expression and activity of voltage-gated channels, inhibiting internalization of dopaminergic receptors, and altering phosphoinositide metabolism. In this study, we examined the possible participation of NCS-1 protein in signal transmission dependent on muscarinic receptor activation, using PC12 cells stably expressing NCS-1 (PC12-NCS-1). Carbachol (CCH; 300 microM) was able to evoke glutamate release more efficiently from PC12-NCS-1 (15.3+/-1.0nmol/mg of protein) than wild type cells (PC12-wt; 8.3+/-0.9nmol/mg of protein). This increase of glutamate release induced by CCH was independent on extracellular Ca2+ influx. Additionally, a larger increase of cytoplasmic levels of InsP3 (663.0+/-63.0 and 310.0+/-39.0% of fluorescence in A.U.) and [Ca2+]i (766.4+/-40.0 and 687.8+/-37.1nmol/L) was observed after CCH stimulus of PC12-NCS-1 compared with PC12-wt. Clearly distinction between intracellular Ca2+ dynamics was also observed in PC12-NCS-1 and PC12-wt. A larger increase followed by fast decay of [Ca2+]i was observed in PC12-NCS-1. A plateau with a delayed decay of [Ca2+]i was characteristic of PC12-wt [Ca2+]i response. Both enhancement of InsP3 production and glutamate release observed in PC12-NCS-1 were blocked by atropine (10 microM). Together, our data show that overexpression of NCS-1 in PC12 cells induces an enhancement of intracellular second messenger and transmitter release dependent on CCH response, suggesting that muscarinic signaling is "up-regulated" in this cell model.
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PMID:Modulation of muscarinic signaling in PC12 cells overexpressing neuronal Ca2+ sensor-1 protein. 1965 67

During the development of the brain, synaptic connections between nerve cells are being established with remarkable specificity. This is achieved by a series of steps: first, axons grow to their terminal areas. Second, axons and dendrites contact each other and select among potential synaptic partners. Third, after synapses have become functional, the fine-tuning of synaptic connections optimizes emerging networks to perform their specific functions. Here, I summarize the evidence for a central role of intracellular calcium signaling in all three stages of the development of specific synaptic connections. In particular, calcium signaling has the capacity to integrate information from a wide array of extracellular factors that are known to regulate neuronal development, such as molecular cues or neuronal activity. Calcium signaling, in turn, directs structural as well as functional adaptations in individual neurons that underlie the establishment of synaptic specificity. Importantly, evidence is accumulating that errors in calcium-dependent network maturation are associated with neurodevelopmental disorders. Therefore, understanding the role of calcium in setting up brain networks may not only advance our insights into mechanisms of normal brain development, but also help identifying the causes of diseases such as autism or mental retardation.
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PMID:Calcium signaling and the development of specific neuronal connections. 1966 Jun 72

Calcium/calmodulin-dependent serine kinase (CASK), a causative gene in X-linked mental retardation, acts as a multi-domain scaffold protein and interacts with more than 20 cellular proteins in different subcellular regions of neurons. It is of interest, therefore, to explore whether post-translational modification regulates CASK's protein-protein interactions. Here, we provide evidence that CASK is phosphorylated by protein kinase A (PKA), identifying residue S562 in the PSD-95-Dlg-ZO-1 domain and residue T724 in the guanylate kinase domain as PKA sites by an in vitro PKA kinase reaction and site-directed mutagenesis. Although the role of S562 phosphorylation is not clear, T724 phosphorylation up-regulates the interaction between CASK and T-box transcription factor T-brain-1 (Tbr-1). NMDAR2b, a downstream target of the CASK-Tbr-1 complex, was then used to explore the significance of CASK phosphorylation by PKA. In cultured cortical neurons, the PKA pathway stimulates both the protein expression and the promoter activity of NMDAR2b. Deletion of the Tbr-1-binding sites greatly reduces the 3'-5'-cyclic AMP responsiveness of the NMDAR2b promoter, and the CASK T724A mutation does not promote the 3'-5'-cyclic AMP responsiveness of NMDAR2b. In conclusion, our data provide evidence that PKA phosphorylates CASK, regulates the nuclear function of CASK, and consequently modulates NMDAR2b expression.
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PMID:CASK phosphorylation by PKA regulates the protein-protein interactions of CASK and expression of the NMDAR2b gene. 2006 77

The purpose of this study was to investigate the effects of physical training and calcium intake on bone mineral density (BMD) of students with mental retardation. Forty mentally retarded boys (age 7-10 years old) were randomly assigned to four groups (no differences in age, BMD, calcium intake and physical activity): training groups with or without calcium supplementation (Tr+Ca+ and Tr+Ca-) and nontraining groups with or without calcium supplementation (Tr-Ca+ and Tr-Ca-). The intervention involved 45 min of physical training performed 3 sessions a week and/or the addition of dietary calcium-rich food using enriched cow milk with vitamin D containing 230 mg calcium per serving, over 6 months. Paired-samples t-test and ANOVA analysis was used to determine the main and combined effects of training and calcium on BMD. All groups showed greater femoral neck BMD after 6 months. The increase in femoral neck BMD in the Tr+Ca+ group was 10% greater than increase in the Tr+Ca- group (not significant). Apparently, the effect of training was greater than calcium intake because the Tr+Ca- group achieved 4% greater BMD than Tr-Ca+ group (not significant). In this study, both training groups had greater BMD than the control group (Tr-Ca-) (P<0.05). In these participants with inadequate calcium intakes, additional exercise and calcium supplementation resulted in a 6-20% greater increase in BMD than controls at the loaded site (femoral neck). These results help to provide more evidence for public health organizations to deal with both exercise and nutrition issues in children for the achievement of peak BMD.
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PMID:Effects of physical training and calcium intake on bone mineral density of students with mental retardation. 2029 86

Williams-Beuren syndrome is a neurodevelopmental disorder mainly characterized by dysmorphic features, vascular stenoses, abnormalities of calcium and glucose metabolism, and mental retardation with visuospatial deficits, caused by de novo deletion of 26-28 genes at 7q11.23. Clinical-molecular correlations have defined critically deleted genes as likely responsible for several aspects of the phenotype, but the precise biological pathways affected are mostly unknown. We performed comparative transcriptome profiling of lymphoblastoid cell lines from four Williams-Beuren syndrome patients and two patients with smaller deletions and partial phenotypes. We detected 92 genes deregulated in all patients and 47 genes deregulated only in Williams-Beuren syndrome, with two additional clusters differentially expressed between both groups. Glycolysis and neuronal migration were the most significantly affected pathways by over-representation analyses. In addition, several genes involved in microtubule formation were specifically deregulated in patients with the common deletion. In summary, comparative expression profiling in lymphoblasts has revealed abnormal regulation of gene pathways potentially related to relevant aspects of the Williams-Beuren syndrome phenotype, including the cognitive, visuospatial and metabolic disturbances.
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PMID:Transcriptome profile in Williams-Beuren syndrome lymphoblast cells reveals gene pathways implicated in glucose intolerance and visuospatial construction deficits. 2040 92

Calcium as a molecule plays a significant role in the body, especially in the central nervous system. In its free form, it has been classified as a cofactor, second messenger, and signaling molecule, and, when bound, forms a protein and coenzyme. This is secondary to the critical, and at times, very sensitive reactions associated with it. Calcium homeostasis, especially in the context of the central nervous system, may have crucial implications in many neuropsychiatric conditions. The hypothesis presented will explore the link between the blood-brain barrier (BBB) and calcium homeostasis (CH) as it is a complex, physiological process. Absence of organic deficits associated with conditions, such as pervasive developmental disorder (PDD), autism spectrum disorders (ASD), mental retardation (MR), and attention deficit hyperactivity disorder (ADHD), in addition to other chronic psychiatric disorders, builds a more compelling case to explore CH in context of the BBB.
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PMID:Blood brain barrier: the role of calcium homeostasis. 2043 65

Non-clustered protocadherins (PCDHs) are calcium-dependent adhesion molecules which have attracted attention for their possible roles in the neuronal circuit formation during development and their implications in the neurological disorders such as autism and mental retardation. Previously, we found that a subset of the non-clustered PCDHs exhibited circuit-dependent expression patterns in thalamo-cortical connections in early postnatal rat brain, but such patterns disappeared in adulthood. In this study, we identified that the non-clustered PCDHs showed differential expression patterns along the septotemporal axis in the subregions of adult hippocampus and dentate gyrus with topographical preferences. The expressions of PCDH1, PCDH9, PCDH10 and PCDH20 showed septal preferences, whereas the expressions of PCDH8, PCDH11, PCDH17 and PCDH19 showed temporal preferences, suggesting that they play roles in the formation/maintenance of intrahippocampal circuits. PCDHs also exhibited the region-specific expression patterns in the areas connected to hippocampal formation such as entorhinal cortex, lateral septum, and basolateral amygdaloid complex. Furthermore, the expression levels of three PCDHs (PCDH8, PCDH19 and PCDH20) were regulated by the electroconvulsive shock stimulation of the brain in the adult hippocampus and dentate gyrus. These results suggest that non-clustered PCDHs are involved in the maintenance and plasticity of adult hippocampal circuitry.
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PMID:The expression of non-clustered protocadherins in adult rat hippocampal formation and the connecting brain regions. 2054 94


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