ISSN:1080-4013    

DOI:10.1002/mrdd.1410010302

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractThis papaer provides an overview of the developmental characteristics of several major CNS neurotransmitter systems, specifically those involving serotonin, catecholamines, and GABA. These were chosen because of their putative importance in various aspects of brain development or plasticity, and the existence of clinically relevant sequelae linking these systems to developmental disorders and disabilities. Patterns of development of these neurotransmitter systems and their putative roles as developmental signals are discussed, as is their possible relevance to developmental disabilities such as autism, attention‐deficit/hyperactivity disorders, self‐injurious behaviour, and epilepsy. © 1995 Wiley‐Lis

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010303

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractGene expression is primarily controlled at the level of transcription. Of the 100,000 genes expressed in the human body, 30–50% may be specifically expressed in nervous tissue. Some of this gene expression is genetically determined and is therefore preprogrammed. However, neuronal gene expression can also be affected by environmental factors, mediated through neuronal transmission. It is hypothesized that neurotransmission has a primary role in developmental and adult neuronal plasticity, and that these effects are mediated through alterations in gene expression. Pathological neurotransmission, such as that seen after seizures, may be disruptive to these patterns of gene expression. © 1995 Wiley‐Liss,

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010304

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractOpiate use has been described for thousands of years. In this century, clinical features of the “neonatal abstinence syndrome” have been amply documented in the medical literature. Indeed, the abuse of “recreational” drugs continues at an alarming rate and results in a high number of adverse maternal‐fetal outcomes even as we near the end of the twentieth century. These consequences persist despite the myriad of medical advances that have resulted in the lowest perinatal mortality on record.The effects of opiate exposure on the developing fetus have been extensively described in the literature on animal research, in which neurodevelopmental and behavioral abnormalities have been linked to brain region‐specific cellular and molecular findings. The human clinical literature clearly defines the symptoms, timing, and frequency of opiate withdrawal in infants exposed prenatally and documents treatment of withdrawal, which is dependent on the severity of symptoms. A panoply of similarities exist.The adverse complications of maternal opiate addiction during the human prenatal and postnatal period are most significant for the fetus and infant, resulting in increased morbidity and mortality. Other consequences include stillbirth, premature birth, low birth weight, small head circumference at birth and during childhood, poor postnatal somatic growth, transient hypertonia, maladaptive responses to physiologic stresses of hypoxia and hypercarbia, and an increased rate of sudden infant death syndrome, as well as a variety of neurodevelopmental and cognitive delays. Although the factors relating to socioeconomic status, nutrition, and multisubstance abuse add to the challenges of acquiring reliable data, a vast amount of animal and human data suggest that opioids play a critical role in developmental processes that affect the vulnerability and plasticity of the immature brain. In addition, affected infants and children are subject to significant emotional, social, and environmental instability throughout their lives. This must certainly contribute to their neurobehavioral dysfunction. Regardless of these findings, opiates do not appear to have a specific teratogenic effect. © 1995 Wil

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010305

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractNeuronal storage diseases are inborn errors of metabolism characterized by widespread intraneuronal storage and progressive neurological dysfunction, including mental retardation, movement disorders, and seizures. Most of these disorders are associated with specific defects in particular lysosomal enzymes. Moreover, a wide array of genetic defects has been documented. The immense progress made during the past three decades in understanding the primary molecular and enzymatic defects in this family of diseases stands in sharp contrast to the modest advances made in delineating pathogenetic mechanisms and treatment strategies. Although these disorders result from highly selective defects in metabolic pathways, they ultimately are complex conditions characterized by a plethora of seemingly unrelated secondary molecular and cellular abnormalities. Studies of children and animals affected by these diseases have revealed that significant changes in neuronal connectivity occur in the cerebral cortex. These include not only degenerative changes in axons and synapses of inhibitory neurons, but also a regrowth of dendrites and new synapse formation involving pyramidal neurons. The latter finding indicates that neurons in the cerebral cortex undergo significant “rewiring” during the height of the disease process. This regrowth of primary dendrites and formation of new synapses as part of a neurological disease is unprecedented. Understanding the causes and consequences of these changes in cortical synaptic connectivity in neuronal storage diseases may provide insight not only into the precise mechanisms underlying mental retardation in these diseases and their reversibility, but also into processes governing dendritic elaboration and synapse formation in the normal developing nervous system. © 1995 Wiley‐Lis

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010306

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractIschemia in the developing brain triggers a series of events that cause damage after a threshold of severity and duration are reached. Release of glutamate, the major excitatory amino acid neurotransmitter in the brain, is one of the primary events in this cascade of injury. Release of glutamate combined with reversal of glutamate uptake pumps in nerve terminals causes glutamate levels to increase from 10–1000x baseline levels in the brain's extracellular space during ischemia, traumatic brain injury, and hypoglycemia in animal models and in humans. High levels of extracellular glutamate trigger opening of N‐methyl‐D‐asparate (NMDA) and non‐NMDA glutamate channels, allowing calcium and sodium to flood into neurons. Energy failure in mitochondria facilitates opening of NMDA channels by lowering the membrane potential and reducing their blockade by magnesium that resides within the channel at normal membrane potentials. Calcium entry into the cytoplasm triggers several events including activation of lipases, proteases, and nucleases that can destroy the neuron's cellular machinery. Generation of reactive oxygen free radicals including the messenger molecule nitric oxide can have additional destructive effects. Drugs that block glutamate receptors and the “excitotoxic cascade” of downstream events can protect the brain from injury and show promise for clinical application in infants and children. © 1995 W

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010307

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractInborn errors of metabolism are associated with a significant risk of mental retardation and other developmental disabilities. Only rarely, is the mechanism of the neural injury clearly understood. This is particularly true for those inborn errors of metabolism associated with hyperammonemia, principally urea cycle disorders and organic acidemias. Previously, it was assumed that elevated ammonia levels alone could account for the brain injury. However, in vitro studies suggest that ammonia is not particularly toxic to intact neurons. Furthermore, there does not appear to be a direct linkage between the peak blood ammonia level during hyperammonemic coma and subsequent neurodevelopmental outcome. There is, however, a correlation between duration of hyperammonemic coma and outcome, suggesting a secondary, time‐influenced mechanism of neural injury. Recent research has focused on excitotoxicity as a possible inducer of neural injury in congenital hyperammonemia. In addition to developmental disabilities, affected children exhibit behavioral abnormalities. An alteration in serotonin metabolism has been proposed as an explanation for these aberrant behaviors during less severe episodes of hyperammonemia. This review focuses on the neurotransmitter abnormalities occuring in congenital hyperammonemia and on new approaches to protecting the brain during hyperammonemic crises. © 1995 Wiley‐Liss,

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010308

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractEpilepsy, a paroxysmal disorder characterized by abnormal neuronal discharges, is common in children. While the causes of epilepsy are many, the fundamental disorder is secondary to abnormal synchronous discharges of a network of neurons. Whether or not a seizure occurs in a child depends upon the balance between excitability and inhibition. Central nervous system neurotransmitters have significant effects on neuronal excitability and play a pivotal role in brain excitability. The most common excitatory neurotransmitter in the brain, glutamate, has been implicated in both the initiation and propagation of seizures as well as brain damage that can occur following prolonged or repeated seizures. Gammaaminobutyric acid, the most common inhibitory neurotransmitter, usually suppresses seizure activity, although in absence seizure drugs that enhance GABA may exacerbate seizures. Experience with GABA indicates that certain neurotransmitters may have either anticonvulsant or proconvulsant effects depending on the neuronal networks involved. While other neurotransmitters also have effects on neuronal excitability, their function in epilepsy remains to be defined. © 1995 Wiley‐Liss, I

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010309

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractAttention‐deficit/hyperactivity disorder is a common neurodevelopmental disorder characterized by short attention span, distractibility, hyperactivity, and impulsivity, which begins in early childhood. The purpose of this review is threefold: to summarize early research suggesting that ADHD results from frontal‐striatal dysfunction and can be ameliorated by medications that increase dopaminergic and noradrenergic transmission: to describe recent functional imaging studies that allow in vivo testing of these hypotheses; and to discuss recent advances in the understanding of neurotransmitter function that may suggest new approaches to elucidating the neurochemical basis of this disor

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010310

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractThis review describes the alterations that occur in a variety of neurotransmitter systems in mouse trisomy 16 and compares those alterations with ones observed in individuals with Down syndrome (Trisomy 21) and Alzheimer's disease. Individuals with Down syndrome who survive into their fourth decade invariably have the neuropathologic and neurochemical features associated with Alzheimer's disease. Thus, comparative studies may provide insight into pathogenetic mechanisms common to all three conditions. These neurotransmitter alterations are accompanied by neuroanatomical as well as neurophysiological alterations in Down syndrome, Alzheimer's disease, and mouse trisomy 16. Because mice with complete trisomy 16 do not survive the perinatal period. Ts 16 neurons placed in culture, as well as primary and secondary chimeras comosed in part of Ts 16 cells, have also been examined for neurotransmitter alterations. Like individuals with Down syndrome, mice with trisomy 16 have triplication of a constellation of genes that have remained together in the same order for roughly 80 million years. As more of these genes have been identified and localized to specific regions of human chromosome 21 and, in some cases, to mouse chromosome 16 as well, effeorts have been made to create mice that are transgenic for these can be studied. Studies of several of these different types of transgenic mice have begun to provide insight inot the mechanisms by which neurotransmitter alterations may arise in Ts 16 mice, and by extrapolation, in DS individuals as well. © 1995 Wiley‐Liss, I

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010311

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY