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)

Monoclonal antibodies exhibiting relative differences in binding to brain homogenates from diseased versus control brains may be useful probes into the molecular pathology of neuropsychiatric illness. To be of value, the antibodies must be useful in characterization of the antigens putatively involved in the illness. An antibody called EP10 showed some differences in binding to homogenates from a small sample of schizophrenia brains compared with controls. In the present study, the antigen for this antibody was characterized in control brains using quantitative, immunocytochemical, and biochemical techniques. The antigen is a 38,000 dalton synaptic vesicle protein, which is identical to synaptophysin by immunological criteria. However, the EP10 epitope is of interest, as this binding site does not appear to be present in rat or bovine synaptophysin. Brain regional studies using EP10 indicate that the antigen may be present in only a subset of synaptic terminals. Further studies are required to fully characterize the epitope, and to determine the significance of the earlier findings related to schizophrenia.
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PMID:Characterization of a synaptic antigen of interest in neuropsychiatric illness. 173 76

It has been proposed that synaptic density or synaptic innervation may be altered in schizophrenia as a correlate of the neurodevelopmental pathology of the disease. Synaptophysin is a synaptic vesicle protein whose distribution and abundance provides a synaptic marker which can be reliably measured in post mortem brain. We have used in situ hybridization histochemistry and immunoreactivity to assess the expression of synaptophysin messenger RNA and protein respectively in medial temporal lobe from seven schizophrenics and 13 controls. In the schizophrenic cases, synaptophysin messenger RNA was reduced bilaterally in CA4, CA3, subiculum and parahippocampal gyrus, with a similar trend in dentate gyrus but no change in CA1. It was also decreased in terms of grains per pyramidal neuron in the affected subfields. In parahippocampal gyrus, the loss of synaptophysin messenger RNA per neuron in schizophrenia was greater in deep than superficial laminae. A parallel study in rats showed no effect of haloperidol treatment upon hippocampal synaptophysin messenger RNA, suggesting that neuroleptic treatment does not underlie the reductions found in schizophrenia. In the right medial temporal lobe of schizophrenics, we confirmed the correlation of synaptophysin messenger RNA abundance between ipsilateral subfields seen in both hemispheres of control brains. However, these correlations were not observed in the left medial temporal lobe of the schizophrenic cases. Synaptophysin immunoreactivity in schizophrenia showed no significant differences in any subfield compared to controls. Our data support the broad hypothesis that synaptic pathology occurs in schizophrenia. In so far as synaptophysin expression is a marker for synaptic density, the data suggest that pyramidal neurons within the medial temporal lobe may form fewer synapses. However, the lack of any significant differences in synaptophysin immunoreactivity despite the loss of encoding messenger RNA means that this conclusion must be drawn cautiously. There are several plausible explanations for the preservation of synaptophysin immunoreactivity despite reductions in transcript abundance; one possibility is that the inferrred loss of synapses occurs in extra-hippocampal sites to which the affected pyramidal neurons project. For example, the reduction in synaptophysin messenger RNA in subicular neurons may be accompanied by decreased density of synaptic terminals in the nucleus accumbens. Such differences in the efferent synaptic connectivity of the hippocampus have previously been hypothesized to be an important component of the circuitry underlying schizophrenia.
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PMID:Altered synaptophysin expression as a marker of synaptic pathology in schizophrenia. 747 74

These studies explore the distribution of putative neuroactive peptides in the human olfactory bulb. Localization of synaptophysin-, serotonin-, cholecystokinin-, substance P-, and somatostatin-like staining was examined by immunocytochemical protocols. The results provide new insights into the composition and laminar segregation of subpopulations of neurons and neuronal processes in the human olfactory bulb. The prominent synaptophysin-like immunoreactivity observed in the glomeruli of the human olfactory bulb is consistent with the notion that the density of synapses, and hence the density of synaptic vesicles, is highest in the glomeruli. Serotonin-like immunoreactivity suggested a variable innervation of glomeruli ranging from a dense tangled ball of fibers within the glomerulus to a sparse innervation by a single immunoreactive fiber. There was no evidence of serotonin-like immunoreactive cell bodies in either the olfactory bulb proper, anterior olfactory nucleus, or proximal regions of the lateral olfactory tract. Cholecystokinin-like immunoreactivity was limited to fibers found largely in the juxtaglomerular region of the glomerular layer. In the deeper layers of the olfactory bulb, cholecystokinin-like immunoreactive fibers did not show any of branching or arborization that was evident in the juxtaglomerular region. Substance P-like immunoreactivity was seen in varicose fibers distributed in all of the human olfactory bulb laminae. In addition, stained multipolar neurons were found in the area of the anterior olfactory nucleus. Somatostatin-like immunoreactivity was similar to that of substance P in that a plexus of stained fibers was found in all laminae of the olfactory bulb. Also, somatostatin-like immunoreactive cell bodies were found in the area of the anterior olfactory nucleus. However, as compared to substance P, somatostatin had a less dense plexus of immunoreactive fibers in the olfactory bulb. These results increase our understanding of the fundamental organization of the human olfactory system. The current data, coupled with prior studies, provide a foundation from which to study the cellular pathology of diseases with known olfactory system sequelae such as Alzheimer's, Parkinson's, and schizophrenia.
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PMID:Immunohistochemical analyses of the human olfactory bulb. 769 Mar 71

The levels of the synaptic vesicle-associated proteins, synapsin and synaptophysin, were examined in human postmortem hippocampus from the brains of schizophrenics and age-matched controls using a quantitative western blot analysis. The schizophrenic samples had significantly lower levels of synapsin I than controls. In individual data, five of the seven schizophrenic samples had extremely low levels of synapsin, whereas two of the schizophrenic samples had normal levels of synapsin. This deficit in synapsin does not appear to be due to some non-specific neuronal loss as the levels of the other synaptic vesicle marker, synaptophysin, were near normal in all seven schizophrenics. Given that synapsin is thought to regulate neurotransmitter release, it is possible that this deficit in synapsin could result in abnormal processing of neuronal information as is seen in various sensory processing abnormalities associated with schizophrenia.
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PMID:Significant reductions in synapsin but not synaptophysin specific activity in the brains of some schizophrenics. 827 80

Synaptic alterations have been suggested, largely on theoretical grounds, to occur in the brain in schizophrenia. The messenger RNA encoding synaptophysin, a presynaptic terminal protein, is reduced in the medial temporal lobe in the disease, but immunocytochemical and immunoblotting data have not produced clear evidence for a loss of the encoded protein. Here we have used immunoautoradiography with an antisynaptophysin monoclonal antibody and a 35S-labelled secondary antibody in medial temporal lobe sections from 11 schizophrenics and 14 matched controls. In the schizophrenic cases there was an overall loss of synaptophysin (P < 0.02). Analysis by subfield showed significant reductions in the right dentate gyrus molecular layer, subiculum and parahippocampal gyrus, with similar trends in most other subfields. These data confirm that synaptophysin expression is decreased within the medial temporal lobe in schizophrenia. In the respect that synaptophysin is a marker of synaptic density, our findings suggest that reduced synaptic density may be a feature of the molecular neuropathology of the disease.
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PMID:Decreased synaptophysin in the medial temporal lobe in schizophrenia demonstrated using immunoautoradiography. 855 31

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 neuronal organization and patterns of afferent innervation are abnormal in the cingulate cortex in schizophrenia, and associated changes in synaptic terminals could be present. A panel of monoclonal antibodies was defined with biochemical and fusion protein studies as detecting syntaxin (antibody SP6), synaptophysin (antibody SP4) and synaptosomal-associated protein-25 (antibody SP12). These antibodies and a polyclonal antibody reactive with neural cell adhesion molecule were used to investigate the cingulate cortex in schizophrenia. Immunocytochemistry indicated that syntaxin immunoreactivity had a considerably wider distribution than synaptophysin. Overall, multivariate analysis indicated increased synaptic terminal protein immunoreactivity in schizophrenia compared to controls (P=0.004). Controlled for age and post mortem interval, syntaxin immunoreactivity was significantly elevated in schizophrenia (P=0.004), and neural cell adhesion molecule immunoreactivity was also elevated (P=0.05). The neural cell adhesion molecule to synaptophysin ratio was increased (P=0.005), possibly indicating the presence of less mature synapses in schizophrenia. Elevated syntaxin immunoreactivity is consistent with increased glutamatergic afferents to the cingulate cortex in schizophrenia, and combined with the neural cell adhesion molecule to synaptophysin ratio results suggests that synaptic function in this region in schizophrenia may be abnormal.
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PMID:Cingulate cortex synaptic terminal proteins and neural cell adhesion molecule in schizophrenia. 913 92

Studies in the past have revealed serotonin to play a role in regulating the development and maturation of the mammalian brain, largely through the release of the astroglial protein S-100beta. S-100beta plays a role in neurite extension, microtubule and dendritic stabilization and regulation of the growth associated protein GAP-43, all of which are key elements in the production of synapses. Depletion of serotonin, and thus of S-100beta, during synaptogenesis should lead to a loss of synapses and the behaviors dependent on those synapses. The current study was undertaken to test this hypothesis. In order to assess the influence of serotonin we have looked at the synaptic density in the adult after depletion, by using immunodensitometry of synaptic markers (synaptophysin and MAP-2) and by studying behaviors thought to be highly dependent on synaptic plasticity and density. Male Sprague-Dawley rats were depleted of serotonin on postnatal days (PND) 10-20 by treating with the tryptophan hydroxylase inhibitor parachlorophenylalanine (PCPA; 100 mg/kg, s.c.). On PND's 30 and 62, animals were perfused for immunodensitometry. Littermates were used for behavioral testing. At PND 55-62, the animals were tested in an interchangeable maze with olfactory cues and in an eight-arm radial maze. Our results show a loss of both synaptic markers in the hippocampus on PND 30. At PND 62, the only remaining loss was of the dendritic marker MAP-2. The animals had deficits in both behaviors tested, suggestive of spacial learning deficits and of the failure to extinguish learned behaviors or to re-learn in a new set. Our findings show the long-term consequences of interfering with the role of serotonin in brain development on the morphology and function of the adult brain. These findings may have implications for human diseases, including schizophrenia, thought to be related to neurodevelopmental insults such as malnutrition, hypoxia, viruses or in utero drug exposure. Moreover, they provide further insights into the functioning of serotonin and S-100beta in development and aging.
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PMID:Serotonin depletion during synaptogenesis leads to decreased synaptic density and learning deficits in the adult rat: a possible model of neurodevelopmental disorders with cognitive deficits. 923 19

Synaptic abnormalities have been implicated in schizophrenia. In order to investigate synaptic pathology in schizophrenia, we examined levels of mRNAs encoding synaptophysin, synapsin 1A and synapsin 1B in the left temporal cortex from schizophrenics (n = 24) and from normal control individuals with no history of psychiatric illness (n = 10). Levels of synaptic mRNAs in the left superior temporal and left middle temporal gyrus declined significantly with age in schizophrenics, but not in controls. Dividing the diagnostic groups according to age (below and above 75 years), the data revealed that in "young" schizophrenics (age <75 years) levels of the three synaptic mRNAs in the left superior and left middle temporal gyri were approximately two times higher than in the age-matched controls. In the "old" schizophrenics (age >75 years) the levels of synaptic mRNAs in temporal cortex did not differ from age-matched controls. These findings further support the hypothesis that developmental synaptic abnormalities may be involved in the pathophysiology of schizophrenia.
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PMID:Age-related abnormalities in expression of mRNAs encoding synapsin 1A, synapsin 1B, and synaptophysin in the temporal cortex of schizophrenics. 930 85

Recent evidence indicates that developmental anomalies may underlie some symptoms of schizophrenia, while psychophysical studies have demonstrated olfactory deficits in this disease. The postmortem olfactory mucosa of elderly schizophrenic patients was examined to characterize the molecular phenotype of this tissue. The distribution of developmentally regulated cytoskeletal proteins, a synaptic vesicle protein, a neural marker protein, a receptor for trophic molecules, axonal guidance and cell migration proteins, and neuronal and glial cytoskeletal proteins of various degrees of phosphorylation was examined by immunohistochemistry. Both schizophrenic and control subjects exhibited dystrophic neurites that were immunoreactive for synaptophysin, microtubule-associated proteins (MAP1B), and neurofilament proteins. No major histochemical or morphologic differences in either the expression or distribution of these proteins were observed in the olfactory epithelium of schizophrenic compared to control subjects. These studies indicated that dystrophic neurites frequently occurred in the olfactory mucosa of both schizophrenics and neurologically normal adults. The absence of major immunocytochemical abnormalities suggested that olfactory deficits in schizophrenia may be due to more subtle cellular or molecular differences or to abnormalities in olfactory regions of the central nervous system rather than in the olfactory epithelium.
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PMID:Human olfactory mucosa in schizophrenia. 955 72


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