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

Studies of the trophic activities of brain-derived neurotrophic factor and neurotrophin-3 indicate that both molecules support the survival of a number of different embryonic cell types in culture. We have shown that mRNAs for brain-derived neurotrophic factor and neurotrophin-3 are localized to specific ventral mesencephalic regions containing dopaminergic cell bodies, including the substantia nigra and ventral tegmental area. In the present study, in situ hybridization with 35S-labeled cRNA probes for the neurotrophin mRNAs was combined with neurotoxin lesions or with immunocytochemistry for the catecholamine-synthesizing enzyme tyrosine hydroxylase to determine whether the dopaminergic neurons, themselves, synthesize the neurotrophins in adult rat midbrain. Following unilateral destruction of the midbrain dopamine cells with 6-hydroxydopamine, a substantial, but incomplete, depletion of brain-derived neurotrophic factor and neurotrophin-3 mRNA-containing cells was observed in the ipsilateral substantia nigra pars compacta and ventral tegmental area. In other rats, combined in situ hybridization and tyrosine hydroxylase immunocytochemistry demonstrated that the vast majority of the neurotrophin mRNA-containing neurons in the substantia nigra and ventral tegmental area were tyrosine hydroxylase immunoreactive. Of the total population of tyrosine hydroxylase-positive cells, double-labeled neurons constituted 25-50% in the ventral tegmental area and 10-30% in the substantia nigra pars compacta, with the proportion being greater in medial pars compacta. In addition, tyrosine hydroxylase/neurotrophin mRNA coexistence was observed in neurons in other mesencephalic regions including the retrorubral field, interfascicular nucleus, rostral and central linear nuclei, dorsal raphe nucleus, and supramammillary region. The present results demonstrate brain-derived neurotrophic factor and neurotrophin-3 expression by adult midbrain dopamine neurons and support the suggestion that these neurotrophins influence dopamine neurons via autocrine or paracrine mechanisms. These data raise the additional possibility that inappropriate expression of the neurotrophins by dopaminergic neurons could contribute to the neuropathology of disease states such as Parkinson's disease and schizophrenia.
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PMID:Dopaminergic neurons in rat ventral midbrain express brain-derived neurotrophic factor and neurotrophin-3 mRNAs. 791 99

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

The Stanley Foundation Brain Collection contains a matched set of specimens from patients diagnosed with schizophrenia, bipolar disorder, non-psychotic depression and normal controls. Specimens have been shipped to investigators in more than 50 laboratories around the world. To date, results obtained from studies with this collection indicate that schizophrenia and bipolar disorder may both be characterized by abnormalities in frontal cortical interneurons, although different subpopulations of these neurons may be specifically affected in the two disorders. In samples from patients with familial bipolar disorder and major depression, there are alterations in glial density in cingulate cortex. Specific effects of antidepressant drugs on the transcription factor cAMP regulatory element binding protein and brain-derived neurotrophic factor have also been observed.
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PMID:Schizophrenia and bipolar disorder: findings from studies of the Stanley Foundation Brain Collection. 1050 26

Previous neuropathological studies have revealed that the corticolimbic system of schizophrenic patients expresses abnormal levels of various synaptic molecules, which are known to be influenced by the neuronal differentiation factors, neurotrophins. Therefore, we determined levels of neurotrophins and their receptors in the postmortem brains of schizophrenic patients and control subjects in relation to molecular impairments in schizophrenia. Among the neurotrophins examined, levels of brain-derived neurotrophic factor (BDNF) were elevated specifically in the anterior cingulate cortex and hippocampus of schizophrenic patients, but levels of nerve growth factors and neurotrophin-3 showed no change in any of the regions examined. In parallel, the expressions of TrkB receptor and calbindin-D, which are both influenced by BDNF, were reduced significantly in the hippocampus or the prefrontal cortex. However, neuroleptic treatment did not appear to mimic the neurotrophic change. Neither withdrawal of drug treatment in patients nor chronic administration of haloperidol to rats altered levels of BDNF. These findings suggest that neurotrophic abnormality is associated with the corticolimbic structures of schizophrenic patients and might provide the molecular substrate for pathological manifestations of the illness.
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PMID:Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients. 1088 32

Neurotrophic factors, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are known to play a crucial role in growth, differentiation and function in a variety of brain neurons during development and in adult life. We have recently shown that environmental changes, aggressive behavior and anxiety-like responses alter both circulating and brain basal NGF levels. In the present review, we present data obtained using animal models which suggest that neurotrophic factors, particularly NGF and BDNF, might be implicated in mechanism(s) leading to a condition associated with schizophrenic-like behaviors. The hypothesis that neurotrophins of the NGF family can be implicated in some maldevelopmental aspects of schizophrenia is supported by findings indicating that the constitutive levels of NGF and BDNF are affected in schizophrenic patients.
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PMID:Studies in animal models and humans suggesting a role of nerve growth factor in schizophrenia-like disorders. 1110 78

The neonatal (PND 7) lesion of the ventral hippocampus (VH) with ibotenic acid represents a well-established experimental paradigm that recapitulates many schizophrenia-like phenomena. In order to investigate molecular changes that could contribute to long lasting consequences on brain function, we have investigated the effects of the VH lesion on the expression for the trophic factors FGF-2 and BDNF. We used RNase protection assay to measure their mRNA levels in cortical regions of prepubertal (PND 35) and young adult (PND 56) animals, both under basal condition as well as in response to an acute restraint stress. The expression of BDNF was not altered by the VH lesion in prefrontal (PFC) and frontal cortex (FC) of PND 35 or PND 56 rats. An acute restraint stress at PND 35 produced a significant increase of the neurotrophin expression in PFC of sham as well as lesioned animals. However in young adult animals a significant elevation of BDNF expression was observed only in sham rats. We also found that the VH lesion produced a significant reduction of basal BDNF mRNA levels in the cingulate cortex of young adult, but not prepubertal rats. This effect was not accompanied by changes in the acute modulation of the neurotrophin, which was up-regulated by stress in both experimental groups. Conversely the expression of FGF-2 at PND 35 and PND 56 was not altered by early postnatal VH lesion, and there were no major differences between sham and lesioned animals in response to the acute stress. The changes in trophic factor expression may be relevant for the long-term effects of VH lesion on synaptic plasticity and may determine an increased vulnerability of the brain under challenging situations.
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PMID:Developmental and stress-related changes of neurotrophic factor gene expression in an animal model of schizophrenia. 1132 96

Clinical studies have shown that there is a genetic contribution to the pathogenesis of schizophrenia. The molecular mechanisms of effective antipsychotic drugs and recent advances in neural development suggest that several dopamine receptor, serotonin receptor and neurotrophic factor genes might be involved in the disorder. In this study, we assessed the associations between schizophrenia and polymorphisms in the D2 and D3 dopamine receptor (DRD2, DRD3), the serotonin 2A receptor (5HTR2A), the brain-derived neurotrophic factor (BDNF), the ciliary neurotrophic factor (CNTF) and the neurotrophin-3 (NT-3) genes. Our results suggest that the polymorphisms at the DRD3, 5HTR2A, CNTF and BDNF gene loci are unlikely to make our sample more genetically susceptible to schizophrenia. However, we found significant differences in microsatellite allele frequencies between schizophrenic and control groups for DRD2 in the whole sample and for DRD2 and NT-3 only in women. Therefore, clinical differences in the presentation of schizophrenia between gender might be related to genetic factors.
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PMID:Association study of schizophrenia with polymorphisms at six candidate genes. 1134 65

Quetiapine is a new atypical antipsychotic drug widely used in the treatment of schizophrenia and other psychotic disorders. This study examined the influence of quetiapine on the decrease of brain-derived neurotrophic factor (BDNF) expression, induced by chronic immobilization stress, in the hippocampus of the rat. Pretreatment with 10 mg/kg of quetiapine markedly attenuated the stress-induced decrease in levels of BDNF protein, as determined by Western blot analyses, and the reduction of BDNF immunoreactivity, in hippocampal pyramidal and dentate granular neurons. These results suggest that the chronic administration of quetiapine could be neuroprotective to hippocampal neurons in schizophrenia and this effect may be related to its antipsychotic effect in patients with schizophrenia.
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PMID:Quetiapine attenuates the immobilization stress-induced decrease of brain-derived neurotrophic factor expression in rat hippocampus. 1187 58

Previous studies have shown that 5-hydroxytryptamine(2A) (5-HT(2A)) receptor activation induces changes in the pattern of brain-derived neurotrophic factor (BDNF) mRNA expression in the neocortex and hippocampus, and that 5-HT(2A) receptor blockade interferes with the induction of BDNF mRNA by stress. Recent studies have also shown that activation of metabotropic glutamate group II (mGlu2/3) receptors suppresses 5-HT(2A) receptor-stimulated excitatory postsynaptic potentials/currents (EPSP/Cs) in pyramidal neurons in medial prefrontal cortex. Conversely, blockade of mGlu2/3 receptors enhances 5-HT-induced EPSCs. The current study examined the effects of the highly selective mGlu2/3 agonist (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate (LY354740) and the mGlu2/3 antagonist 2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3(xanthy-9-yl)propanoic acid (LY341495) on BDNF mRNA expression in medial prefrontal cortex induced by the hallucinogen and 5-HT(2A/2B/2C) agonist 1-(2,5-dimethoxy-4-iodophenethyl)-2-aminopropane (DOI). LY354740 (0.1-10 mg/kg) dose-dependently suppressed DOI-induced BDNF mRNA levels in medial prefrontal cortex. In contrast, the mGlu2/3 antagonist LY341495 (1 mg/kg) enhanced DOI-induced BDNF mRNA levels. BDNF mRNA expression was not altered by administration of the mGlu agonist or the antagonist alone. These results are discussed with respect to a potential role for group II mGlu agonists in the treatment of depression and schizophrenia.
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PMID:Modulation of DOI-induced increases in cortical BDNF expression by group II mGlu receptors. 1211 85


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