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)

The authors examined the frequency of cells with polyploidy-P, with amitot division-AD and with mitotic division-MD in 25 patients with schizophrenia and proven anticerebral autoimmune sensibilization by means of blast-transformation test-BS, in 20 partners of marriages with multiple spontaneous abortions and suspected isoimmunization-PCA as well as control group of 63 healthy adults and newborn infants. Simultaneous increase of the frequency of cells with polyploidy and amitotic division was established in patients with schizophrenia--1,16% of P and 0.40% AD in 4 women with spontaneous abortiosn -- 1.5% of P and 0.80% of AD compared with the control values of 0.54% of P and 0.17% of AD. The highest percentage P -- 1.12 and AD -- 2.1 was found in BS with chronic process, in whom the blast-transformation reaction to brain antigen --34% was mostly manifested. In the cultures of BS, treated with brain antigen, AD reached up to 1.38%. The increase of AD was accompanied with lowering of mitotic index: BS -- 1.2% of MD and 0.40 of AD; PSA -- 2,04% of MD and 0.50 of AD compared with the control values of 4% of MD and 0.17% of AD. The results showed that immunologic sensibilization was accompanied by an increase of genome mutations and amitotic division and with lowering of mitotic index; they revealed polyploidy and amitotic division as compensatory mechanisms of the organisms under certain conditions.
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PMID:[Correlation between genome mutations and the cell division types in immunological sensitization states]. 49 37

The regulated expression of neural cell adhesion molecule (NCAM) isoforms in the brain is critical for many neurodevelopmental processes including neurulation, axonal outgrowth, and the establishment of neuronal connectivity. We have investigated the expression of the major adult isoforms of NCAM (NCAM-180, NCAM-140, and NCAM-120) and its embryonic highly polysialylated isoform (PSA-NCAM) in the hippocampal region of postmortem brains from 10 schizophrenic and 11 control individuals. Immunohistochemical analysis with a monoclonal antibody recognizing the PSA-NCAM revealed immunoreactivity primarily in the dentate gyrus and in a subset of cells in the hilus region. We have observed a 20-95% reduction in the number of hilar PSA-NCAM-immunoreactive cells in the great majority of schizophrenic brains. The change in PSA-NCAM immunoreactivity is not obvious in other hippocampal subfields. Western blots of tissues from the hippocampal region (as well as from the frontal cortex) probed with a polyclonal antibody recognizing all NCAM isoforms did not reveal significant changes in the overall expression of NCAM, suggesting that the decrease in PSA-NCAM-immunoreactive cells may be related to post-translational processing of the molecule. The expression of this embryonic form of NCAM has been proposed to be related to synaptic rearrangement and plasticity. Therefore, the decrease in PSA-NCAM immunoreactivity in schizophrenic hippocampi may suggest an altered plasticity of this structure in a large proportion of schizophrenic brains. These findings may bear significance to the "neurodevelopmental hypothesis" of schizophrenia.
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PMID:Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brains. 770 24

The addition of poly-alpha2,8-N-acetylneuraminic acid (polysialic acid; PSA) to the neural cell adhesion molecule NCAM plays a crucial role in neural development [1-3], neural regeneration [4], and plastic processes in the vertebrate brain associated with neurite outgrowth [5], axonal pathfinding [6], and learning and memory [7,-9]. PSA levels are decreased in people affected by schizophrenia [10], and PSA has been identified as a specific marker for some neuroendocrine and lymphoblastoid tumours [11-13]; expression of PSA on the surface of these tumour cells modulates their metastatic potential [11-13]. Studies aimed at understanding PSA biosynthesis and the dynamics of its production have largely been promoted by the cloning of polysialyltransferases (PST-1 in hamster; PST in human and mouse) [14-16]. However, the number of enzymes involved in the biosynthesis of PSA has not been identified. Using incompletely glycosylated NCAM variants and soluble recombinant glycosyltransferases, we reconstituted the site at which PST-1 acts to polysialylate NCAM in vitro. The data presented here clearly demonstrate that polysialylation of NCAM is catalyzed by a single enzyme, PST-1, and that terminal sialylation of the N-glycan core is sufficient to generate the PSA acceptor site. Our results also show that PST-1 can act on core structures with the terminal sialic acid connected to galactose via an alpha2,3 or alpha2,6 linkage.
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PMID:Polysialylation of NCAM by a single enzyme. 880 71

The hypothesis of a neurodevelopmental dysfunction being involved in the etiology of schizophrenia is suggested by the observation of morphological alterations in the brains of schizophrenia patients. These alterations may be caused by defects in neural cell differentiation or migration, which could lead to disrupted neuronal circuitry and to the schizophrenia symptomatology. The neural cell adhesion molecule (NCAM) plays a major role in cell migration and axon outgrowth, and is involved in synaptic plasticity mechanisms implicated in adult cognitive functions. Altered levels of the NCAM polysialylated form, PSA-NCAM, in the brain of schizophrenia patients have been reported, and are supportive of a role for this molecule in the disorder. To investigate the possible involvement of the NCAM gene in schizophrenia, we conducted a comprehensive genetic study, which included linkage analysis and an association study employing the Haplotype Relative Risk (HRR) design in nuclear families. Our results indicate that structural alterations in the NCAM gene are unlikely to play a major role in schizophrenia, although a function for the NCAM molecule in the etiology of the disease remains an intriguing hypothesis.
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PMID:NCAM and schizophrenia: genetic studies. 915 19

Modulation of neural cell adhesion molecule polysialylation (NCAM PSA) state has been proposed to underlie morphofunctional change associated with consolidation of memory in the rodent, and its age-dependent decline to be related to impaired cognitive function. To establish whether this may be a human correlate of cognitive decline, we determined the age-dependent expression of PSA in the human hippocampal dentate gyrus using postmortem tissue derived from individuals who exhibited no obvious neuropathology. As in the rodent, PSA immunoreactivity in the 5-month human infant was associated mainly with a population of granule-like cells and their mossy fibre axons. Cell numbers were maximal during the first 3 years of life but declined by an order of magnitude between the second and third decades and remained relatively constant thereafter and was restricted to the granule cell layer/hilar border. In contrast to the rodent, diffuse immunostaining was observed in the inner molecular layer; however, as development advanced, this became relocated to the outer molecular layer from 2 years of age onwards. In addition, numerous polysialylated hilar neurons became evident at 2-3 years of age and remained constant until the eighth decade of life. These findings suggest NCAM polysialylation to play a crucial developmental role within a period concluding with adolescence, and that an attenuated NCAM PSA-mediated neuroplasticity continues throughout the human lifespan. The importance of the developmental phase of NCAM PSA expression in the emergence of schizophrenia is discussed.
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PMID:Polysialylated neural cell adhesion molecule expression in the dentate gyrus of the human hippocampal formation from infancy to old age. 989 Apr 38

We have investigated the deposition of glycoconjugates in human brain tissue with or without brain disorders. In this review we describe the application of lectin-histochemistry techniques to forensic neuropathology. Lectin staining is able to reveal several kinds of carbohydrate-related depositions in addition to the conventional degenerative changes including senile plaques, neurofibrillary tangles and corpora amylacea. The senile plaques and neurofibrillary tangles were clearly stained by Con A, PSA and GSI lectins, the corpora amylacea which is relevant to repeated brain hypoxia and mitochondrial damage was also easily detected by these and many other kinds of lectins. Amorphous spaces were detected around blood vessels and independently from blood vessels by lectin staining in the white matter from patients with brain disorders or severe edema. The white matter lesions were not considered relevant for forensic pathology, until a large group of cerebral white matter lesions were detected in the elderly with increasing frequency by modern neuro-imaging methods. The spherical deposits were newly detected by lectin staining in the molecular layer of the dentate gyrus of the hippocampal formation chiefly from patients with schizophrenia or cognitive dysfunctions.
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PMID:Utilization of lectin-histochemistry in forensic neuropathology: lectin staining provides useful information for postmortem diagnosis in forensic neuropathology. 1456 71

Chandelier neurons and their characteristic arrays of axonal terminals, known as cartridges, have been implicated in a variety of psychiatric and neurological disorders including schizophrenia and epilepsy. As a result, these neurons have been extensively examined in the brains of several species using a range of markers. However, these markers have not been systematically compared in a single species for their robustness in labelling chandelier cell cartridges. We have therefore examined several markers, reported to label chandelier arrays in primates, for their capacity to mark these structures in rat medial prefrontal cortex and hippocampus. These studies revealed that cartridge-like structures were labelled by parvalbumin and GAT-1 immunohistochemistry in both medial prefrontal cortex and hippocampus of the rat brain. Additionally, GAD65 immunohistochemistry labelled array-like structures preferentially in the dentate gyrus. In contrast, PSA-NCAM, calbindin and GAD67 immunohistochemistry did not reveal any array-like structures in either region of rat brain. These observations indicate that the various immunological markers previously used to visualise chandelier cell cartridges in primates are not equally efficient in labelling these structures in the rat brain, and that GAT-1 immunohistochemistry is the most robust means of visualising chandelier cell cartridges in the regions examined. These are important considerations for quantitative studies in animal models of neurological disorders where chandelier neurons are implicated.
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PMID:A comparison of possible markers for chandelier cartridges in rat medial prefrontal cortex and hippocampus. 1564 49

Neuroimaging has revealed structural abnormalities in the amygdala of different psychiatric disorders. The polysialylated neural cell adhesion molecule (PSA-NCAM), a molecule related to neuronal structural plasticity, which expression is altered in schizophrenia, major depression and in animal models of these disorders, may participate in these changes. However, PSA-NCAM has not been studied in the human amygdala. To know whether its expression and that of presynaptic markers, was affected in psychiatric disorders, we have analyzed post-mortem sections from the Stanley Neuropathology Consortium, which includes controls, schizophrenia, bipolar and major depression patients. PSA-NCAM was expressed in neuronal somata and neuropil puncta, many of which corresponded to interneurons. Depressed patients showed decreases in PSA-NCAM expression in the basolateral and basomedial amygdala; synaptophysin and GAD67 were also decreased, while VGLUT-1 was increased, in different nuclei. Increases in PSA-NCAM expression were found in the lateral nucleus of bipolar patients; synaptophysin and GAD67 were reduced, and VGLUT-1 increased, in their basolateral and lateral nuclei. The expression of synaptophysin and GAD67 was downregulated in the basolateral nucleus of schizophrenics. These results indicate that inhibitory and excitatory amygdaloid circuits are affected in these disorders and that abnormal PSA-NCAM expression in depressive and bipolar patients may underlie these alterations.
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PMID:Expression of PSA-NCAM and synaptic proteins in the amygdala of psychiatric disorder patients. 2209 65

Decreased expression of dopamine D2 receptors (D2R), dysfunction of inhibitory neurotransmission and impairments in the structure and connectivity of neurons in the medial prefrontal cortex (mPFC) are involved in the pathogenesis of schizophrenia and major depression, but the relationship between these changes remains unclear. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, may serve as a link. This molecule is expressed in cortical interneurons and dopamine, via D2R, modulates its expression in parallel to that of proteins related to synapses and inhibitory neurotransmission, suggesting that D2R-targeted antipsychotics/antidepressants may act by affecting the plasticity of mPFC inhibitory circuits. To understand the role of PSA-NCAM in this plasticity, rats were chronically treated with a D2R agonist (PPHT) after cortical PSA depletion. PPHT-induced increases in GAD67 and synaptophysin (SYN) neuropil expression were blocked when PSA was previously removed, indicating a role for PSA-NCAM in this plasticity. The number of PSA-NCAM expressing interneuron somata also increased after PPHT treatment, but the percentages of these cells belonging to different interneuronal subpopulations did not change. Cortical pyramidal neurons did not express PSA-NCAM, but puncta co-expressing this molecule and parvalbumin could be found surrounding their somata. PPHT treatment increased the number of PSA-NCAM and parvalbumin expressing perisomatic puncta, but decreased the percentage of parvalbumin puncta that co-expressed SYN. PSA depletion did not block these effects on the perisomatic region, but increased further the number of parvalbumin expressing puncta and increased the percentage of puncta co-expressing SYN and parvalbumin, suggesting that the polysialylation of NCAM may regulate perisomatic inhibition of mPFC principal neurons. Summarizing, the present results indicate that dopamine acting on D2R influences structural plasticity of mPFC interneurons and point to PSA-NCAM as a key player in this remodeling.
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PMID:Polysialic acid is required for dopamine D2 receptor-mediated plasticity involving inhibitory circuits of the rat medial prefrontal cortex. 2221 1

Several lines of evidence indicate that alterations in the structure of neural circuits and inhibitory neurotransmission underlie the physiopathogenesis of schizophrenia. Most of the studies on these parameters have been focused on cortical regions and, despite the crucial role of the amygdala in this psychiatric disorder, there is less information on this region. In order to expand this knowledge, we have studied the expression of molecules related to inhibitory neurotransmission and structural plasticity in rats subjected to post-weaning isolation rearing, an animal model that reproduces several core symptoms of schizophrenia. We have analyzed, using qRT-PCR and immunohistochemistry, the expression of synaptophysin, GAD65, GAD67, the neural cell adhesion molecule (NCAM), its polysialylated form (PSA-NCAM) and its synthesizing enzymes (St8siaII and St8SiaIV). Isolation-reared rats showed significant increases in the expression of GAD67 protein in the centromedial, medial and basolateral amygdaloid nuclei, but no significant changes in GAD65 or synaptophysin expression were found in these regions. The expression of PSA-NCAM and NCAM was significantly increased in the basolateral and medial nuclei respectively. Our results indicate that isolation-rearing influences positively inhibitory neurotransmission and neuronal structural plasticity in the amygdala, probably through PSA-NCAM. These findings are in contrast to reports describing decreased expression of molecules related to inhibitory neurotransmission in the amygdala of schizophrenic patients. Consequently, although the social isolation rearing model can reproduce some of the behavioral traits of schizophrenics it may fail to reproduce some of the neurobiological features of this disorder, particularly in the amygdala.
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PMID:Post-weaning social isolation rearing influences the expression of molecules related to inhibitory neurotransmission and structural plasticity in the amygdala of adult rats. 2235 88


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