Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electroconvulsive therapy is used in the treatment of affective disorders and schizophrenia and experimental electroconvulsive shock may serve as an animal model for this treatment. The aim of this study was to investigate a possible role for neurotrophins in the mechanism of action of experimental electroconvulsive shock and thus in clinical electroconvulsive therapy. The effect of electroconvulsive shock on levels of messenger RNAs encoding the neurotrophin brain-derived neurotrophic factor and the receptor trkB in rat hippocampus was determined by in situ hybridization with RNA probes 1, 3, 9 and 27 h following the shock. Brain-derived neurotrophic factor messenger RNA levels were increased at 1, 3 and 9 h following the shock and normalized after 27 h. Granule cells of the dentate gyrus showed a more rapid response as compared to hilar cells and pyramidal cells of CA1. Total trkB messenger RNA levels, including the transcripts for both the truncated and full length trkB receptor protein (gp95trkB and gp145trkB, respectively), showed a pattern of increase very similar to that of the brain-derived neurotrophic factor messenger RNA. However, using a probe selective for the full length (gp145trkB) trkB messenger RNA, we determined a delayed pattern of activation with significant increase only at 3 and 9 h after the shock. In hippocampus total trkB messenger RNA was found to consist of approximately one-quarter of mRNA encoding gp145trkB and three-quarters encoding gp95trkB as revealed by RNAase protection. While brain-derived neurotrophic factor and the truncated trkB messenger RNAs appear to increase with a similar pattern, suggesting a similar mechanism of activation by electroconvulsive shock, full length receptor trkB messenger RNA appears to increase with a delayed pattern suggesting a separate mechanism of activation. Electroconvulsive shock-induced seizures seem to include activation of a brain neurotrophin known to be important for neuronal plasticity.
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PMID:Spatiotemporal selective effects on brain-derived neurotrophic factor and trkB messenger RNA in rat hippocampus by electroconvulsive shock. 760 68

Developmental or degenerative damage of the neuronal architecture in the entorhinal cortex may disintegrate a functional part of hippocampal input since the entorhinal cortex provides a major source of neocortical and subcortical input to the hippocampus. These alterations, such as seen in Alzheimer's disease, schizophrenia and temporal lobe epilepsy are likely to be associated with cognitive deficits. To understand the basis for pathological changes in the corticohippocampal loop it is important to study mechanisms involved in neuronal plasticity. Brain-derived neurotrophic factor provides a possible substrate to mediate such plasticity. We have previously provided evidence that stimulation of hippocampal afferents transynaptically increase the level of brain-derived neurotrophic factor messenger RNA within the hippocampus. In the present study we have investigated whether different brain-derived neurotrophic factor messenger RNAs are specifically regulated in the hippocampus. We provide evidence for a differential and dose-dependent regulation of the different brain-derived neurotrophic factor promoters in the hippocampus by afferents in the entorhinal cortex. Our finding of a graded regulation is in contrast to earlier evidence of an "all-or-none" type of regulation.
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PMID:Entorhinal cortex regulation of multiple brain-derived neurotrophic factor promoters in the rat hippocampus. 830 50

There is increasing evidence that a neurodevelopmental process is accountable for at least a proportion of schizophrenic cases. Brain-derived neurotrophic factor (BDNF), a member of a group of proteins that includes neurotrophin-3/4/5 and nerve growth factor (NGF), is an attractive candidate gene. We have performed a case control association study using the BDNF dinucleotide repeat polymorphism in a sample of familial schizophrenic individuals and in healthy, ethnically matched control subjects. We also performed a linkage analysis on 265 multiplex families using the same marker. We found no differences in allele frequencies between the patient and control groups nor any evidence for transmission disequilibrium or linkage with the multiply affected families. We conclude that DNA variation at or near the BDNF gene is unlikely to contribute to the genetic predisposition to schizophrenia.
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PMID:No linkage or linkage disequilibrium between brain-derived neurotrophic factor (BDNF) dinucleotide repeat polymorphism and schizophrenia in Irish families. 985 28

The antipsychotics haloperidol and risperidone are widely used in the therapy of schizophrenia. The former drug mainly acts on the dopamine (DA) D(2) receptor whereas risperidone binds to both DA and serotonin (5HT) receptors, particularly in the neurons of striatal and limbic structures. Recent evidence suggests that neurotrophins might also be involved in antipsychotic action in the central nervous system (CNS). We have previously reported that haloperidol and risperidone significantly affect brain nerve growth factor (NGF) level suggesting that these drugs influence the turnover of endogenous growth factors. Brain-derived neurotrophic factor (BDNF) supports survival and differentiation of developing and mature brain DA neurons. We hypothesized that treatments with haloperidol or risperidone will affect synthesis/release of brain BDNF and tested this hypothesis by measuring BDNF and TrkB in rat brain regions after a 29-day-treatment with haloperidol or risperidone added to chow. Drug treatments had no effects on weight of brain regions. Chronic administration of these drugs, however, altered BDNF synthesis or release and expression of TrkB-immunoreactivity within the brain. Both haloperidol and risperidone significantly decreased BDNF concentrations in frontal cortex, occipital cortex and hippocampus and decreased or increased TrkB receptors in selected brain structures. Because BDNF can act on a variety of CNS neurons, it is reasonable to hypothesize that alteration of brain level of this neurotrophin could constitute one of the mechanisms of action of antipsychotic drugs. These observations also support the possibility that neurotrophic factors play a role in altered brain function in schizophrenic disorders.
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PMID:Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain are significantly altered after haloperidol and risperidone administration. 1086 91

Brain-derived neurotrophic factor (BDNF), like other neurotrophins, is a polypeptidic factor initially regarded to be responsible for neuron proliferation, differentiation and survival, through its uptake at nerve terminals and retrograde transport to the cell body. A more diverse role for BDNF has emerged progressively from observations showing that it is also transported anterogradely, is released on neuron depolarization, and triggers rapid intracellular signals and action potentials in central neurons. Here we report that BDNF elicits long-term neuronal adaptations by controlling the responsiveness of its target neurons to the important neurotransmitter, dopamine. Using lesions and gene-targeted mice lacking BDNF, we show that BDNF from dopamine neurons is responsible for inducing normal expression of the dopamine D3 receptor in nucleus accumbens both during development and in adulthood. BDNF from corticostriatal neurons also induces behavioural sensitization, by triggering overexpression of the D3 receptor in striatum of hemiparkinsonian rats. Our results suggest that BDNF may be an important determinant of pathophysiological conditions such as drug addiction, schizophrenia or Parkinson's disease, in which D3 receptor expression is abnormal.
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PMID:BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. 1133 82

Brain-derived neurotrophic factor (BDNF) plays an important role in development, synapse remodelling and responses to stress and injury. Its abnormal expression has been implicated in schizophrenia, a neuropsychiatric disorder in which abnormal neural development of the hippocampus and prefrontal cortex has been postulated. To clarify the effects of antipsychotic drugs used in the therapy of schizophrenia on BDNF mRNA, we studied its expression in rats treated with clozapine and haloperidol and in rats with neonatal lesions of the ventral hippocampus, used as an animal model of schizophrenia. Both antipsychotic drugs reduced BDNF expression in the hippocampus of control rats, but did not significantly lower its expression in the prefrontal cortex. The neonatal hippocampal lesion itself suppressed BDNF mRNA expression in the dentate gyrus and tended to reduce its expression in the prefrontal cortex. These results indicate that, unlike antidepressants, antipsychotics down-regulate BDNF mRNA, and suggest that their therapeutic properties are not mediated by stimulation of this neurotrophin. To the extent that the lesioned rat models some pathophysiological aspects of schizophrenia, our data suggest that a neurodevelopmental insult might suppress expression of the neurotrophin in certain brain regions.
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PMID:BDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs. 1148 57

Brain-derived neurotrophic factor (BDNF) belongs to a family of proteins related to nerve growth factor, which are responsible for neuron proliferation, survival and differentiation. A more diverse role for BDNF as a neuronal extracellular transmitter has, nevertheless, been proposed. The dopamine D(3) receptor has been implicated in neuropsychiatric disorders including schizophrenia, drug addiction, depression and Parkinson's disease. Its expression during development and in adulthood is highly dependent on dopaminergic innervation. Here we show that BDNF synthesized by dopamine neurons is responsible for the appearance of the D(3) receptor during development and maintains D(3) receptor expression in adults. Moreover, BDNF triggers D(3) receptor overexpression and behavioral sensitization to levodopa in denervated animals. These results suggest that BDNF, by controlling the expression of specific genes such as the D(3) receptor gene, may be an important factor in neurodevelopmental psychiatric diseases.
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PMID:Brain-derived neurotrophic factor controls dopamine D3 receptor expression: implications for neurodevelopmental psychiatric disorders. 1270 5

Brain-derived neurotrophic factor (BDNF) promotes a variety of neuromodulatory processes during development as well as in adulthood. This neurotrophin has been associated with synaptic plasticity, suggesting that its regulation may represent one of the mechanisms through which psychotropic drugs alter brain function. Because reduced glutamatergic function represents a major feature of schizophrenia, we investigated the effects of the concomitant administration of haloperidol or olanzapine with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on BDNF expression. MK-801 reduces the hippocampal expression of the neurotrophin; this effect was exacerbated by haloperidol, but it was normalized by olanzapine. Our data reveal a fine tuning of BDNF biosynthesis and a differential modulation by antipsychotic drugs when NMDA-mediated transmission is reduced, suggesting that haloperidol and olanzapine can produce different effects on brain plasticity through the modulation of BDNF expression.
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PMID:Effect of antipsychotic drugs on brain-derived neurotrophic factor expression under reduced N-methyl-D-aspartate receptor activity. 1274 27

Brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the etiology of schizophrenia. There is a line of evidence that disruption of neurotrophins could play a role in the etiology of schizophrenia, and antipsychotics show their effect by altering levels of neurotrophins. The aim of this study was to evaluate the effect of antipsychotics on serum BDNF levels and their relationship with the symptoms in patients with schizophrenia. Twenty-two schizophrenia patients were enrolled in the study. The control group consisted of 22 age- and sex-matched physically and mentally healthy volunteers (7 male, 15 female). Serum BDNF levels and the positive and negative syndrome scale (PANSS) scores were recorded at baseline and after 6 weeks of treatment. Serum BDNF levels were also recorded in the control group. Schizophrenia patients who failed to meet 30% improvement in PANSS score were excluded from the study. The baseline serum BDNF levels of schizophrenia patients were lower than those of controls (t = 4.56; df = 21; p < 0.001). There was no correlation between serum BDNF levels and PANSS scores in patients with schizophrenia (p > 0.05). Although PANSS (for positive symptoms p < 0.001, for negative symptoms p < 0.001) and general psychopathology (t = 20.9; df = 22; p < 0.001) scores improved significantly after 6 weeks of antipsychotic treatment; there was no change in BDNF levels in patients' serum (p > 0.05). Our results support the view that BDNF would be associated with schizophrenia. However, we could not conclude that treatment with antipsychotics alters serum BDNF levels in patients with schizophrenia.
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PMID:Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment. 1527 97

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of schizophrenia and bipolar disorder. A functional polymorphism Val66Met of BDNF gene was studied in patients with schizophrenia (n=336), bipolar affective disorder (n=352) and healthy controls (n=375). Consensus diagnosis by at least two psychiatrists, according to DSM-IV and ICD-10 criteria, was made for each patient using a structured clinical interview for DSM-IV Axis I disorders (SCID). No association was found between the studied polymorphism and schizophrenia or bipolar affective disorder either for genotype or allele distribution (for genotype: p=0.210 in schizophrenia, p=0.400 in bipolar disorder; for alleles: p=0.260 in schizophrenia, p=0.406 in bipolar disorder). Results were also not significant when analysed by gender. For males genotype distribution and allele frequency were (respectively): p=0.480 and p=0.312 in schizophrenia, p=0.819 and p=0.673 in bipolar affective disorder. Genotype distribution and allele frequency observed in the female group were: p=0.258 for genotypes, p=0.482 for alleles in schizophrenia; p=0.432 for genotypes, p=0.464 for alleles in bipolar affective disorder. A subgroup of schizophrenic (n=62) and bipolar affective patients (n=28) with early age at onset (18 years or younger) was analysed (p=0.328 for genotypes, p=0.253 for alleles in schizophrenia; p=0.032 for genotypes, p=0.858 for alleles in bipolar affective disorder).
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PMID:Association analysis of brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism in schizophrenia and bipolar affective disorder. 1554 16


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