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)

Cells from the olfactory epithelium of adult human cadavers have been propagated in primary culture and subsequently cloned. These cells exhibit neuronal properties including: neuron-specific enolase, olfactory marker protein, neurofilaments, and growth-associated protein 43. Simultaneously, the cells exhibit nonneuronal properties such as glial fibrillary acidic protein and keratin, the latter suggesting properties of neuroblasts or stem cells. These clonal cultures contain 5-10% of cells sufficiently differentiated to show odorant-dependent cyclic adenosine 3',5'-monophosphate (cAMP) or calcium-release responses when challenged with submicromolar concentrations of odorants. The potential of culturing neuronal cells from patients with neuropsychiatric disorders, such as Alzheimer's disease or schizophrenia, could enable the study of the pathophysiology of these neurons in the culture dish and allow new approaches to the study of mental illness.
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PMID:Continuous culture of neuronal cells from adult human olfactory epithelium. 132 Sep 21

Immunocytochemical staining for glial fibrillary acidic protein (GFAP) allows more specific identification of astrocytes and their processes than classical histochemical techniques and has therefore recently been used by some investigators to quantify gliosis. However, although the immunocytochemical method is superior for delineation of reactive astrocytes, the examples presented here and previous work by others demonstrate that chronic fibrillary gliosis may be best detected by Holzer's method and not by GFAP immunocytochemistry. The authors' studies indicate that if, as in a recent study of gliosis in schizophrenia, computer-assisted densitometry is to be used to measure gliosis, the immunoperoxidase method may not be a sensitive technique to demonstrate glial changes in human postmortem material.
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PMID:Comparison of immunocytochemical and Holzer's methods for detection of acute and chronic gliosis in human postmortem material. 850 47

The authors describe an autopsy case of glioblastoma occurred after 38 years received lobotomy. The patient was a 72 year-old male, who received lobotomy at 34 year old against schizophrenia. CT scan taken at 72 year old showed irregular low density areas without mass effect in the bilateral frontal white matter adjacent to the anterior horn. After 4 months, the signs of intracranial hypertension were observed and his consciousness was disturbed abruptly. CT scan revealed ring enhancement with marked mass effect in the left frontal lobe. A biopsy specimen from the tumor showed a picture of anaplastic astrocytoma. Family rejected the remission maintenance treatment. The patient died 3 months later the onset. At autopsy, a large tumor occupied in the left frontal lobe was recognized. The tumor demarcated poorly from the cerebral tissue and invaded into the left anterior cingulate gyrus and the corpus callosum. Histologically, tumor cells composed of fibrillary, gemistocytic and multinucleated astrocytes. GFAP, NSE and vimentin were found in large cells. Histological diagnosis was glioblastoma. It was suggested that the tumor occurred from the region around a cyst of prefrontal lobotomy in the left frontal lobe. In the right frontal lobe, a large cyst in size of 30-18 mm was present in the centrum semiovale. The wall of cyst was composed of layer of glial scar tissue. The origin of the cyst was discussed.
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PMID:[An autopsy case of glioblastoma occurred in the region after lobotomy]. 207 52

Enzyme immunoassay of the glial fibrillary acid antigen and its antibodies in body fluids with the concentration range of 1 to 128 ng/ml. The technique was applied to study the blood serum content of GFAP and the corresponding antibodies in febrile schizophrenic patients. The data proved the technique valuable as an additional means of diagnostic and verification of effectiveness in the treatment of febrile schizophrenia.
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PMID:[Permeability of the hemato-encephalic barrier in critical states due to febrile schizophrenia]. 313 51

Clinical and neuropsychological studies of chronically institutionalized patients with schizophrenia indicate that severe cognitive impairment and functional disability in late life are very prevalent. The biological substrates for this dementia remain unknown. While subtle cytoarchitectural and morphometric abnormalities have been described in patients with schizophrenia and interpreted as reflecting aberrant neurodevelopment, postmaturational injury or neurodegeneration associated with gliosis remain as plausible explanations of at least some of the clinical manifestations of schizophrenia. We monitored astrocytosis and neurofibrillary tangle (NFT) formation in 21 elderly patients with schizophrenia (14 with concurrent dementia, 7 without), and in 12 normal and 5 Alzheimer's disease (AD) control cases. Astrocytes in ventromedial temporal, frontal, and calcarine cortices were immunohistochemically identified with monoclonal antibodies directed at glial fibrillary acidic protein (GFAP) and vimentin, and NFTs were labeled with an anti-tau antibody specific for paired helical filaments. There were no increases in GFAP- or vimentin-immunoreactive astrocyte counts, GFAP optical density, or NFT counts for the schizophrenic group as a whole compared to the non-neuropsychiatric group, while both groups differed from AD. When patients with schizophrenia were divided into demented and non-demented subtypes, those with dementia demonstrated significantly greater numbers of GFAP-positive astrocytes than those without dementia. These data may reflect an up-regulation of GFAP in normal astrocytes or the presence of reactive astrocytosis in a subgroup of schizophrenics. In the absence of any diagnostic neuropathological findings in this subgroup, the implications of these observations for the pathogenesis of schizophrenia remain to be determined.
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PMID:Glial fibrillary acidic protein-immunoreactive astrocytosis in elderly patients with schizophrenia and dementia. 883 39

The pathophysiology of schizophrenia may involve perturbations of synaptic organization during development. The presence of cytoarchitectural abnormalities that may reflect such perturbations in the brains of patients with this disorder has been well-documented. Yet the mechanistic basis for these features of the disorder is still unknown. We hypothesized that altered regulation of the neuronal growth-associated protein GAP-43, a membrane phosphoprotein found at high levels in the developing brain, may play a role in the alterations in brain structure and function observed in schizophrenia. In the mature human brain, GAP-43 remains enriched primarily in association cortices and in the hippocampus, and it has been suggested that this protein marks circuits involved in the acquisition, processing, and/or storage of new information. Because these processes are known to be altered in schizophrenia, we proposed that GAP-43 levels might be altered in this disorder. Quantitative immunoblots revealed that the expression of GAP-43 is increased preferentially in the visual association and frontal cortices of schizophrenic patients, and that these changes are not present in other neuropsychiatric conditions requiring similar treatments. Examination of the levels of additional markers in the brain revealed that the levels of the synaptic vesicle protein synaptophysin are reduced in the same areas, but that the abundance of the astrocytic marker of neurodegeneration, the glial fibrillary acidic protein, is unchanged. In situ hybridization histochemistry was used to show that the laminar pattern of GAP-43 expression appears unaltered in schizophrenia. We propose that schizophrenia is associated with a perturbed organization of synaptic connections in distinct cortical associative areas of the human brain, and that increased levels of GAP-43 are one manifestation of this dysfunctional organization.
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PMID:Levels of the growth-associated protein GAP-43 are selectively increased in association cortices in schizophrenia. 894 81

The neural cell adhesion molecule (N-CAM) is a cell recognition molecule that is involved in cellular migration, synaptic plasticity, and CNS development. In schizophrenia, a 105- to 115-kDa N-CAM protein is increased in CSF and in the hippocampus and prefrontal cortex. The variable alternatively spliced exon (VASE) of N-CAM is developmentally regulated and can be spliced into any of the major 120-, 140-, and 180-kDa N-CAM isoforms. We determined that the variable alternative spliced exon of N-CAM (VASE) also is increased in bipolar disorder by quantitative Western immunoblot. VASE immunoreactive proteins (triplet bands around 140 kDa and a single band around 145 kDa) were identified in soluble and membrane brain extracts and quantified in the hippocampus. Soluble VASE 140 kDa was increased in the hippocampus of patients with bipolar disorder as compared to controls, patients with schizophrenia, and suicide cases. Membrane-extracted VASE 140 and 145 kDa were unchanged in the same groups. Multiple 145-kDa VASE-immunoreactive proteins that also reacted to an N-CAM antibody were separated by isoelectric focusing and electrophoresis followed by western immunoblotting; however, the VASE 140-kDa proteins were only weakly N-CAM immunoreactive. By immunohistochemistry, VASE colocalized with GFAP-positive astrocytes in the hippocampus. VASE immunostaining was also observed in the cytoplasm of CA4 pyramidal neurons that were positive for phosphorylated high molecular weight neurofilament and synaptophysin terminals. Thus no differences in VASE were found in patients with schizophrenia, but there was a marked increase of VASE immunoreactive proteins in bipolar disorder. It is possible that abnormal regulation of N-CAM proteins results in differing patterns of abnormal expression in neuropsychiatric disorders.
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PMID:VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia. 987 62

Excitotoxins, such as kainic acid (KA), have been shown to produce both immediate and delayed neuronal degeneration in adult rat brain. While preweanling rats have been shown to be resistant to the immediate neurotoxicity of KA, the presence of delayed neuronal loss has not been investigated in such animals. To determine whether intracerebroventricular (i.c.v.) administration of KA would produce delayed neuronal loss, preweanling rats were administered 5 nmol or 10 nmol KA i.c.v. on postnatal day 7 (P7) and then examined at P14, P45, and P75. Using three-dimensional, non-biased cell counting, neuronal loss was observed in the CA3 subfield of the hippocampal formation at P45 and P75 in animals administered 10 nmol KA, as compared to animals administered 5 nmol KA or artificial cerebrospinal fluid. Further, the amount of immunoreactivity to jun, the protein product of the immediate early gene, c-jun, adjusted for the number of remaining neurons was increased in the same brain areas. Antibody labeling of inducible heat shock protein and glial fibrillary acidic protein was not similarly increased in animals administered i.c.v. KA. The data suggest that while i.c.v. KA does not produce immediate neuronal loss in preweanling rats, the hippocampus is altered so that neuronal loss occurs after a delay, perhaps through apoptosis. These findings may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia, that are characterized by early limbic-cortical deficits but onset of illness in young adulthood.
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PMID:Delayed neuronal loss after administration of intracerebroventricular kainic acid to preweanling rats. 997 64

An impairment of prefrontal cortical functioning in schizophrenia ('hypofrontality') has been suggested by clinical, neuroimaging, and postmortem brain tissue studies. We used Western immunoblot and Northern hybridization analyses of postmortem brain tissue obtained from 14 schizophrenic patients and 12 control patients of similar ages to measure tissue levels of synaptophysin (a structural synaptic vesicle protein) and of SNAP-25 (a 25-kDa presynaptic protein), and their encoding mRNAs, in Brodmann's area 10 of prefrontal cortex. There were significant decreases in tissue levels of both of these proteins in prefrontal cortex of schizophrenic patients relative to controls. In contrast, tissue levels for the mRNAs encoding these proteins were not decreased in schizophrenic patients. Subsequent labeling of the same Western immunoblots showed no difference in tissue levels of glial fibrillary acidic protein (GFAP) in schizophrenic and control patients. Similarly, subsequent hybridization of the same Northern hybridization membranes showed no difference in tissue levels of GFAP mRNA or of 28S rRNA in schizophrenic and control patients. These alterations in tissue levels of synaptophysin and SNAP-25 are consistent with the idea that the clinically observed 'hypofrontality' of schizophrenia arises from abnormalities of synaptic number or structural integrity in prefrontal cortex.
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PMID:Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for 'hypofrontality'. 1008 7

Schizophrenia is clinically and neuropsychologically characterized by severe cognitive and functional impairment suggesting the presence of a neurodegenerative process in the brains of affected individuals. A variety of neuroanatomical changes have been described such as loss and disorientation of neurons in grey and white matter and cortical atrophy. However, the neuropathological basis for schizophrenia is still unclear. In the present study we monitored the density of GFAP-positive astrocytes in brains of 33 schizophrenic patients and 26 healthy controls. Both grey matter (entorhinal cortex and subiculum) and white matter (premotor cortex, subventricular zone of the third ventricle and next to inferior horn) structures were measured bilaterally. The overall finding was that there is no evidence for increased astrogliosis in brains of schizophrenic patients vs healthy controls. Therefore, degeneration is unlikely to be the main neuropathological mechanism in schizophrenic brains.
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PMID:No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem study. 1019 75


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