Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There has been little exploration of major biologic regulators of cerebral development in autism. In archived neonatal blood of children with autistic spectrum disorders (n = 69), mental retardation without autism (n = 60), or cerebral palsy (CP, n = 63) and of control children (n = 54), we used recycling immunoaffinity chromatography to measure the neuropeptides substance P (SP), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), and the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4/5 (NT4/5). Neonatal concentrations of VIP, CGRP, BDNF, and NT4/5 were higher (ANOVA, all p values < 0.0001 by Scheffe test for pairwise differences) in children in the autistic spectrum and in those with mental retardation without autism than in control children. In 99% of children with autism and 97% with mental retardation, levels of at least one of these substances exceeded those of all control children. Concentrations were similar in subgroups of the autistic spectrum (core syndrome with or without mental retardation, other autistic spectrum disorders with or without mental retardation) and in the presence or absence of a history of regression. Among children with mental retardation, concentrations did not differ by severity or known cause (n = 11, including 4 with Down syndrome). Concentrations of measured substances were similar in children with CP as compared with control subjects. SP, PACAP, NGF, and NT3 were not different by diagnostic group. No measured analyte distinguished children with autism from children with mental retardation alone. In autism and in a heterogeneous group of disorders of cognitive function, overexpression of certain neuropeptides and neurotrophins was observed in peripheral blood drawn in the first days of life.
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PMID:Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. 1135 50

The maturational changes in the brain and spinal cord do not linearly proceed from immature in infants to mature in adults. Dendrites dynamically extend or retract as neurotrophic factors fluctuate. In certain cases mature neurons can be seen soon after birth, and in other cases immature neurons can be identified in the aged brain. Monoamine 'neurotransmitter'; such as serotonin (5-HT), dopamine and norepinephrine appear to function as Maintenance Growth Factors since they must be present in order to produce their maturational actions. Serotonin neurons contain TRK-B receptors and are sensitive to availability of the trophic factor, BDNF. 5-HT also functions by promoting the release of the glial extension factor, S-100beta. 5-HT and S-100beta can provide maturational signals to a variety of neurons, in both cortical and subcortical areas, and appear to be involved in regulating the maturation and release of acetylcholine and dopamine. We have shown that activation of the 5-HT1A receptor is particularly effective in inducing growth of stunted neurons. The mechanism of action of the 5-HT1A receptor involves both a direct inhibition on c-AMP and pCREB formation in postsynaptic neurons and a release of S-100beta from glial cells. Both these events are capable of stabilization and elaboration of the cytoskeleton of the neuron and inhibition of apoptosis. 5-HT1A receptors have been shown to effectively reverse stunted neurons and microencephaly produced in animal models of fetal alcohol syndrome and prenatal cocaine administration. I discuss the implications for regressive disorders such as Rett's syndrome and autism, and the feasibility of treatments with 5-HT1A agonists in children with developmental disorders.
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PMID:Neuronal instability: implications for Rett's syndrome. 1173 34

We studied the possible involvement of ten candidate genes in autism: proenkephalin, prodynorphin, and proprotein convertase subtilisin/kexin type 2 (opioid metabolism); tyrosine hydroxylase, dopamine receptors D2 and D5, monoamine oxidases A and B (monoaminergic system); brain-derived neurotrophic factor, and neural cell adhesion molecule (involved in neurodevelopment). Thirty-eight families with two affected siblings and one family with two affected half-siblings, recruited by the Paris Autism Research International Sibpair Study (PARIS), were tested using the transmission disequilibrium test and two-point affected sib-pair linkage analysis. We found no evidence for association or linkage with intragenic or linked markers. Our family sample has good power for detecting a linkage disequilibrium of 0.80. Thus, these genes are unlikely to play a major role in the families studied, but further studies in a much larger sample would be needed to highlight weaker genetic effects.
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PMID:Analysis of ten candidate genes in autism by association and linkage. 1185 71

Many different microbial factors seem to contribute to the pathogenesis of schizophrenic and other psychiatric disorders. Activation of all T lymphocytes reactivates those downregulated by low-grade chronic infections and restores equilibrium in immune cell subpopulations. Different immune cell subpopulations express different neurotrophin receptors and produce different cytokines, particularly brain-derived neurotrophin (BDNF) and neurotrophin 3 (NT3) [M. Besser, R. Wank, J. Immunol. 162 (1998) 6303-6306] that appear to play a key role in schizophrenic and bipolar disorders [E. Jonsson, S. Brene, X.R. Zhang, et al., Acta Psychiatr. Scand. 95 (1997) 414-419; R.S. Duman, Arch. Gen. Psychiatry 54 (1997) 597-606; J.A. Siuciak, D.R. Lewis, S.J. Wiegand, R.M. Lindsay, Pharmacol. Biochem. Be 56 (1997) 131-137]. The hypothesis that adoptive immunotherapy is effective in psychiatric disorders will be supported by three case reports, in a patient with bipolar disorder, a patient with schizophrenia, and a patient with autism.
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PMID:Schizophrenia and other mental disorders require long-term adoptive immunotherapy. 1220 1

Rett syndrome is characterized by disruption of a period of vigorous brain growth with synapse development. Neurotrophic factors are important regulators of neuronal growth, differentiation, and survival during early brain development. The aims of this study were to study the role of neurotrophic factors in Rett syndrome, specifically whether Rett syndrome has abnormal levels of specific neurotrophic factors in serum and cerebrospinal fluid and whether the changes differ from other neuropediatric patients, for example, those with infantile autism. Four neurotrophic factors were measured: nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor 1 from the frozen cerebrospinal fluid and from serum (except glial cell line-derived neurotrophic factor) by enzyme-linked immunosorbent assay and cerebrospinal fluid glutamate and aspartate by high-performance liquid chromatography (HPLC) method in patients with Rett syndrome. Insulin-like growth factor 1 was measured from the cerebrospinal fluid of patients with infantile autism. We found low concentrations of cerebrospinal fluid nerve growth factor in patients with Rett syndrome compared with control patients. The serum levels and other cerebrospinal fluid neurotrophic factor levels of the patients did not differ from the controls. Patients with Rett syndrome had high cerebrospinal fluid glutamate levels. Patients with infantile autism had low cerebrospinal fluid insulin-like growth factor 1 levels. Nerve growth factor acts especially on cholinergic neurons of the basal forebrain, whereas insulin-like growth factor 1 acts on cerebellar neurons. In Rett syndrome, the forebrain is more severely affected than the other cortical areas. In autism, many studies show hippocampal or cerebellar pathology. Our findings are in agreement with the different morphologic and neurochemical findings (brain growth, affected brain areas, neurotransmitter metabolism) in the two syndromes. Impairment in dendritic development in Rett syndrome could be the consequence of cholinergic deficiency and of neurotrophic factor/glutamate imbalance. Cholinergic gene expression might be influenced by the Rett syndrome gene directly or via the neurotrophic factor system.
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PMID:Neurotrophic factors in the pathogenesis of Rett syndrome. 1464 51

Perinatal asphyxia is a concern for public health and may promote subtle neuropsychiatric disorders. Anoxic insults to neonatal rats cause long-lasting neurobehavioral deficits. In the present study, we focussed on changes in emotional behaviors as a consequence of neonatal asphyxia in Wistar rats. Newborn pups (24 h after birth) underwent a single 30-min exposure to a 100% N2 atmosphere (or air). The offspring was tested for a) locomotor and exploratory activity with or without a d-amphetamine challenge (0, 1, or 2 mg/kg) on postnatal day (pnd) 15; b) social interactions and novelty seeking during adolescence; c) levels of the brain-derived neurotrophic factor (BDNF). In the open-field test (pnd 15), N2-exposed pups injected with the high (2 mg/kg) amphetamine dose exhibited reduced levels of locomotor hyperactivity, and a more marked involvement in stereotyped behaviors. Individual differences emerged in the locomotor response to the novelty-seeking test: two subgroups of rats (separated on the basis of the median value) showed either arousal/attraction or avoidance/inhibition in response to free-choice novelty. The N2-exposed group showed a more marked novelty-induced avoidance and inhibition. Time devoted to allogrooming and play-soliciting behaviors was reduced, whereas object exploration was increased. Levels of BDNF were reduced in the striatum of N2-exposed rats, suggesting poorer synaptic performance of dopamine pathways. In conclusion, these findings suggest an increased risk of developing social withdrawal, neophobia and behavioral stereotypies (common symptoms found in schizophrenia and autism) as a consequence of neonatal asphyxia in preterm humans.
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PMID:Social withdrawal, neophobia, and stereotyped behavior in developing rats exposed to neonatal asphyxia. 1498 24

Infection of the central nervous system by Borna disease virus (BDV) provides a unique model to study the mechanisms whereby a persistent viral infection can impair neuronal function and cause behavioral diseases reminiscent of mood disorders, schizophrenia, or autism in humans. In the present work, we studied the effect of BDV infection on the response of hippocampal neurons, the main target for this virus, to the neurotrophin BDNF. We showed that persistent infection did not affect neuronal survival or morphology. However, it blocked BDNF-induced ERK 1/2 phosphorylation, despite normal expression of the TrkB BDNF receptor. In addition, BDNF-induced expression of synaptic vesicle proteins was abrogated, which resulted in severely impaired synaptogenesis and defects in synaptic organization. Thus, we provide the first evidence that a virus can interfere specifically with neurotrophin-regulated neuroplasticity, thereby hampering proper neuronal connectivity. These results may help to understand the behavioral disorders associated with BDV infection.
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PMID:Persistent, noncytolytic infection of neurons by Borna disease virus interferes with ERK 1/2 signaling and abrogates BDNF-induced synaptogenesis. 1503 26

To evaluate the availability of the serum neurotrophins for the diagnosis of the patients with neurodevelopmental disorder, we measured the serum concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) in the patients diagnosed with autism (n=18) and mental retardation (n=20), or healthy controls (n=16), using enzyme-linked immunosorbent assay. There tended to be a higher concentration of serum BDNF found in the autistic group ( P <0.05 by analysis of variance (ANOVA)) and the mental retardation group ( P <0.001 by ANOVA) compared to the control group. Serum NT-4 concentration tended to be increased in the mental retardation group (P <0.05 by ANOVA). We conclude that measuring the serum concentration of two neurotrophins, BDNF and NT-4, might be helpful to diagnose or classify disorders such as autism or mental retardation.
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PMID:Serum neurotrophin concentrations in autism and mental retardation: a pilot study. 1516 68

Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching, neurogenesis, gene expression, and improved learning and memory. Moreover, in animal models of CNS insult (e.g., gene deletion), a more complex environment has attenuated or prevented the sequelae of the insult. Of relevance is the prevention of seizures and attenuation of their neuropathological sequelae as a consequence of exposure to a more complex environment. Relatively little attention, however, has been given to the issue of sensitive periods associated with such effects, the relative importance of social versus inanimate stimulation, or the unique contribution of exercise. Our studies have examined the effects of environmental complexity on the development of the restricted, repetitive behavior commonly observed in individuals with autism. In this model, a more complex environment substantially attenuates the development of the spontaneous and persistent stereotypies observed in deer mice reared in standard laboratory cages. Our findings support a sensitive period for such effects and suggest that early enrichment may have persistent neuroprotective effects after the animal is returned to a standard cage environment. Attenuation or prevention of repetitive behavior by environmental complexity was associated with increased neuronal metabolic activity, increased dendritic spine density, and elevated neurotrophin (BDNF) levels in brain regions that are part of cortical-basal ganglia circuitry. These effects were not observed in limbic areas such as the hippocampus.
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PMID:Environmental complexity and central nervous system development and function. 1536 62

Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females. Regression is a defining feature of RTT. During the regression stage, RTT girls display many autistic features, such as loss of communication and social skills, poor eye contact, and lack of interest, and initially may be given the diagnosis of autism. The discovery of the genetic cause of RTT, mutations in the MECP2 gene, a transcriptional repressor, has promoted the early diagnosis of RTT and development of mouse models. The phenotype of one mouse model includes features such as regression and abnormal behavioral and social interactions. The timing of the period of regression in RTT--during ages 1 to 2 years--parallels the period of intense synaptic development. The effects of the MECP2 mutation also increases concomitantly with peak synaptogenesis. Neuropathological findings in Rett include the selective reduction of dendritric spines in the pyramidal cells of RTT brains; this feature has also been reported in autism. Studies have observed that MECP influences the expression of brain-derived neurotrophic factor and thus may influence synaptic plasticity. Abnormalities in synapse maintenance and modulation may contribute to regression in RTT and autism. Studies of the clinical aspects of the regression period and of the mouse model may be useful in understanding the pathophysiology of RTT and other neurodevelopmental disorders such as autism. A recent study observed abnormal expression of MeCP2 in RTT and other neurodevelopmental disorders such as autism. Although the genetic background and certain clinical features differ in RTT and autism, a similar mechanism involving MeCP2 regulation and expression may contribute to regression.
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PMID:Rett syndrome: of girls and mice--lessons for regression in autism. 1536 75


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