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)

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

The neuronal ceroid lipofuscinoses (NCL) are a large group of autosomal recessive lysosomal storage disorders with both enzymatic deficiency and structural protein dysfunction. Previously, diagnosis of NCL was based on age at onset and clinicopathological (C-P) findings described 4 forms, classified as infantile (INCL) (2), late-infantile (LINCL) (5), juvenile (JNCL) (6), and adult (ANCL) (12). Most patients with NCL have progressive ocular and cerebral dysfunction, including cognitive/motor dysfunction and uncontrolled seizures. After reviewing 520 patients with NCL, we found that about 104 (20%) did not fit this classification of NCL. With further research, 4 additional forms have been recognized: Finnish (13), Gypsy/Indian (14), Turkish (15)--variants of LINCL, and Northern epilepsy (16), also known as progressive epilepsy with mental retardation. These eight NCL forms resulted from 151 different mutations in genes CLN1 to CLN8 causing different phenotypes (http://www.ucl.ac.uk/ncl). The genes CLN1 and CLN2 encode lysosomal palmitoyl protein thioesterase and tripeptidyl peptidase 1. The diagnosis of NCL is based on clinicopathological (C-P) findings, enzymatic assay, and molecular genetic testing. Ultrastructural studies must be performed to confirm the presence and nature of lysosomal storage material (fingerprint or curvilinear profiles, or granular osmiophilic deposits) before doing biochemical testing. Pheno/genotypic correlation studies are discussed.
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PMID:Current state of clinical and morphological features in human NCL. 1499 38

Smith Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion of chromosome 17p11.2. The neurobehavioral phenotype of SMS includes mental retardation, speech delay, hyperactivity, attention deficit, decreased sensitivity to pain, self-injury, aggressive behavior and sleep disturbance. Therefore, we performed anatomical and functional brain imaging studies in five SMS boys. Anatomical magnetic resonance imaging (MRI) was analyzed using optimized voxel-based morphometry (VBM). This method can detect structural anomalies not apparent on visual inspection of the scans. Two comparison groups with similar mean age were studied: Group A with 12 healthy control children and Group B with 5 children with idiopathic mental retardation. In addition, positron emission tomography (PET) and water-labeled method were used to investigate a putative localized brain dysfunction in SMS. The control group was composed of mentally retarded children (Group B). A significant bilateral decrease of grey matter concentration was detected in the insula and lenticular nucleus in SMS children. In addition, a significant hypoperfusion was found in the same regions in SMS. These anatomo-functional evidences of bilateral insulo-lenticular anomalies in SMS are consistent with neurobehavioral symptoms of the disease. The identification of localized brain anomalies in SMS may help in understanding how this well-defined genetic entity can lead to a relatively specific severe neurobehavioral syndrome.
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PMID:Anatomical and functional brain imaging evidence of lenticulo-insular anomalies in Smith Magenis syndrome. 1500 69

Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inherited neurometabolic disorder clinically characterized by epilepsy and mental retardation and biochemically by accumulation of guanidinoacetate (GAA) and depletion of creatine. Although the neurological symptoms are predominant, the pathogenesis of the brain dysfunction in this disorder is not yet established. In the present study we investigated the in vitro effect of GAA on Na+, K+-ATPase and Mg2+-ATPase activities in synaptic plasma membrane from hippocampus of young rats. Results showed that GAA significantly inhibited Na+, K+-ATPase activity without affecting Mg2+-ATPase activity. We also evaluated the effect of glutathione (GSH), trolox, Nomega-nitro-L-arginine methyl ester (L-NAME) and taurine (Tau) on the inhibition elicited by GAA on Na+, K+-ATPase activity. GSH, trolox, L-NAME and Tau per se did not alter Na+, K+-ATPase activity. However, L-NAME and taurine prevented the inhibitory effect of GAA on this enzyme activity. Our findings suggest that the inhibition of Na+, K+-ATPase activity caused by GAA is possibly mediated by nitric oxide (NO) formation and/or synaptic membrane alteration. The present data may contribute to the understanding of the neurological dysfunction characteristic of GAMT-deficient patients.
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PMID:Evaluation of the mechanism underlying the inhibitory effect of guanidinoacetate on brain Na+, K+-ATPase activity. 1524 54

The authors report on a series of 72 patients (57 male, 15 female; aged from 4 to 21 years) affected by autism with the aim of evaluate their experience regarding the prevalence of seizure and/or epilepsy. Patients were divided into two groups: the first includes individuals (n = 54) affected by so-called idiopathic or primary autism which was further subdivided according to the grade of mental retardation (MR) and the second (n = 18) in which a known pathological event was associated to the autism (secondary autism). According to these results in the first group 12 % of autistic patients with moderate MR (i.e., IQ > 55) suffered from seizures but in three patients (9 %) they were occasional and only in one recurrent (i.e., epileptic) (3 %). Autistic patients with severe MR (i.e., IQ < 55) suffered from seizures in 20 % of the cases: in three the episodes were recurrent (15 %) and in one occasional (5 %). In the second group in which autism was associated to other morbidities 61 % (n = 11/18) had seizures, being recurrent in 10 (55 %). According to this series, in autism the risk of epilepsy is higher compared to the general population but it does not seem to be correlated to the autism itself, but rather to the associated co-morbidities and underlying brain dysfunction (overall prevalence of epilepsy in primary autism [4/54 or 7.4 %] vs. secondary autism [10/18 or 55 %]).
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PMID:Epilepsy is not a prominent feature of primary autism. 1532 58

A pyramidal neuron in the adult brain has numerous dendritic spines, which are typical postsynaptic structures. The shapes of spines are abnormal in the case of mental retardation, epilepsy, or Fragile X syndrome. Since the spine is thought to be a fundamental element in synaptic function, the abnormal shape of the spine is thought to be directly associated with brain dysfunction in the above diseases. Spine shape is regulated by each cytoskeletal protein. Over-expression of drebrin, a major actin-binding protein in the spine, elongates the spine. In the brain of Alzheimer's disease and Down syndrome, drebrin is greatly reduced. This indicates the structural abnormality of the spine as pathogenesis in the dementia. Now the spine morphogenesis comes into the spotlight. Although spines are thought to be formed from dendritic filopodia, the conversion mechanism of filopodia to spines has not been fully elucidated. We have recently demonstrated that cluster formation of drebrin-actin complex in filopodia is a key step for this conversion. When the cluster formation is inhibited, PSD-95 is not accumulated at postsynaptic sites. Since the drebrin-A isoform is necessary for the cluster formation, the regulation of drebrin A expression is now a focus in the field of spine formation.
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PMID:[Synaptic development and abnormality at protein level]. 1548 28

Neurodevelopmental disorders such as autism, attention deficit disorder, mental retardation, and cerebral palsy are common, costly, and can cause lifelong disability. Their causes are mostly unknown. A few industrial chemicals (eg, lead, methylmercury, polychlorinated biphenyls [PCBs], arsenic, and toluene) are recognised causes of neurodevelopmental disorders and subclinical brain dysfunction. Exposure to these chemicals during early fetal development can cause brain injury at doses much lower than those affecting adult brain function. Recognition of these risks has led to evidence-based programmes of prevention, such as elimination of lead additives in petrol. Although these prevention campaigns are highly successful, most were initiated only after substantial delays. Another 200 chemicals are known to cause clinical neurotoxic effects in adults. Despite an absence of systematic testing, many additional chemicals have been shown to be neurotoxic in laboratory models. The toxic effects of such chemicals in the developing human brain are not known and they are not regulated to protect children. The two main impediments to prevention of neurodevelopmental deficits of chemical origin are the great gaps in testing chemicals for developmental neurotoxicity and the high level of proof required for regulation. New, precautionary approaches that recognise the unique vulnerability of the developing brain are needed for testing and control of chemicals.
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PMID:Developmental neurotoxicity of industrial chemicals. 1787 17

Outcome data were analysed from 780 patients newly diagnosed with epilepsy and followed up at a single centre over a 20-year period to investigate which clinical factors predicted pharmacoresistance. Patients were divided at the time of analysis into those whose seizures had been controlled for at least the last 12 months of follow up (n=462) and those whose epilepsy remained refractory (n=318). Numbers of pre-treatment seizures were greater in uncontrolled patients. Those reporting more than 10 seizures prior to initiation of therapy were more than twice as likely to develop refractory epilepsy. Univariate and multivariate logistic regression analyses demonstrated that pharmacoresistance was also associated with family history of epilepsy, previous febrile seizures, traumatic brain injury as the cause of the epilepsy, intermittent recreational drug use, and prior or current psychiatric comorbidity, particularly depression. Factors not predicting poorer outcome included gender, neurological deficit and mental retardation. The most interesting new finding was the correlation between psychiatric comorbidity and lack of response to antiepileptic drug therapy. The deleterious neurobiological processes that underpin depression, anxiety and psychosis may interact with those producing seizures to increase the extent of brain dysfunction and thereby the likelihood of developing pharmacoresistant epilepsy.
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PMID:Predictors of pharmacoresistant epilepsy. 1762 29

Trisomy 21, one of the most prevalent congenital birth defects, results in a constellation of phenotypes collectively termed Down syndrome (DS). Mental retardation and motor and sensory deficits are among the many debilitating symptoms of DS. Alterations in brain growth and synaptic development are thought to underlie the cognitive impairments in DS, but the role of early brain development has not been studied because of the lack of embryonic human tissue and because of breeding difficulties in mouse models of DS. We generated a breeding colony of the Ts65Dn mouse model of DS to test the hypothesis that early defects in embryonic brain development are a component of brain dysfunction in DS. We found substantial delays in prenatal growth of the Ts65Dn cerebral cortex and hippocampus because of longer cell cycle duration and reduced neurogenesis from the ventricular zone neural precursor population. In addition, the Ts65Dn neocortex remains hypocellular after birth and there is a lasting decrease in synaptic development beginning in the first postnatal week. These results demonstrate that specific abnormalities in embryonic forebrain precursor cells precede early deficits in synaptogenesis and may underlie the postnatal disabilities in Ts65Dn and DS. The early prenatal period is therefore an important new window for possible therapeutic amelioration of the cognitive symptoms in DS.
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PMID:Defects in embryonic neurogenesis and initial synapse formation in the forebrain of the Ts65Dn mouse model of Down syndrome. 1795 91

Autism is a behavioural syndrome, present from early life and defined by deficient social interaction, language and communication, and play. Variations in symptomatology and in prognosis among characteristic persons display a variety of other signs such as attention deficits, mental retardation and seizures that are not specific to autism and that denote dysfunction in other brain systems. Its aetiology is unknown in the vast majority of cases. There is a small minority of persons in whom autism has a known aetiology, such as fragile X chromosome abnormality, congenital rubella, tuberous sclerosis and a variety of structural abnormalities and metabolic diseases of the brain. A causal treatment is so far not possible, and there remains a regrettable lack of evaluated treatment standards. Prognosis depends on many factors, most notably the limiting factor provided by the severity of the underlying brain dysfunction and its consequences for communication, cognition and other behaviour. ENT specialists are confronted with children, adolescents and even adults in whom autistic disease has already been diagnosed in the course of investigations/treatment. If the suspicion of hearing impairment as the cause of problems in daily life is not confirmed in a patient not hitherto known to have autism ENT specialists should also consider autism in the differential diagnosis. In this report the diagnostic and therapeutic strategies currently applied for autism and its importance for ENT specialists are presented.
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PMID:[Autism spectrum disorders. Current knowledge and importance for ENT specialists]. 1821 5


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