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)

Enkephalin immunoreactivity is used to divide the feline substantia innominata into circumscript subregions, i.e. the "striatopallidal system" and the "extended amygdala". In addition, enkephalin immunoreactivity is used to subdivide the striatopallidal system into two distinct areas, i.e. the subcommissural part of the globus pallidus displaying high enkephalin immunoreactivity and the ventral pallidum displaying moderate enkephalin immunoreactivity. The anterograde axonal transport of Phaseolus vulgaris-leucoagglutinin is used to study the efferents of these areas innervating the caudate nucleus and the nucleus accumbens. It is found that the enkephalin-immunoreactive subcommissural part of the globus pallidus as well as the dorsal enkephalin-immunoreactive regions of the extended amygdala project topographically along a rostrocaudal and mediolateral dimension to the nucleus accumbens. The far rostral parts of the caudate nucleus are found to be innervated by the subcommissural part of the globus pallidus whereas the extended amygdala has no such connection. This pathway is also found to be topographically organized along a mediolateral dimension. The non-enkephalin-immunoreactive area ventral and lateral to the subcommissural part of the globus pallidus is found to have no projections to the nucleus accumbens and caudate nucleus. This region rather innervates the olfactory tubercle. In contrast to the striatopallidal system the sublenticular part of the extended amygdala preferentially projects to the adjoining part of the extended amygdala, i.e. the bed nucleus of the stria terminalis. However, the ventral regions preferentially innervate the medial division of the bed nucleus of the stria terminalis whereas the dorsal regions preferentially innervate the lateral division of the bed nucleus of the stria terminalis. These data indicate that the differential forebrain systems represented in the feline substantia innominata, i.e. the striatopallidal system and extended amygdala have differential output stations. The results are discussed in view of the role of the subcommissural part of the globus pallidus and the nucleus accumbens in orofacial dyskinesia and schizophrenia, respectively.
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PMID:Efferent connections of the striatopallidal and amygdaloid components of the substantia innominata in the cat: projections to the nucleus accumbens and caudate nucleus. 194 94

This study attempted to identify microscopic correlates to the structural abnormalities reported in the corpus callosum of schizophrenic patients. Sections of the genu, body, and splenium of the corpus callosum were taken from formalin-fixed brains of deceased patients with schizophrenia and nonschizophrenic control subjects. Photomicrographs of stained tissue were projected, and nerve fibers were counted. There were no significant differences (p greater than 0.4) in axonal counts between schizophrenic and control patients for any of the sites sampled. Our results suggest that morphometric abnormalities of the corpus callosum of schizophrenic patients, if present, are not the consequence of a primary process within this structure.
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PMID:Axonal counts of the corpus callosum of schizophrenic patients. 252 Oct 88

Cortex is not preprogrammed to recognise transthalamic sensory patterns or to prioritize them for motor reaction. Network subsets for these abilities are taught into neocortex in early life from the hippocampi where species-significant pattern-recognition and reaction-prioritizing ARE genetically preprogrammed. Thereafter whenever an indoctrinated subset of cortex is activated via thalamic sensory relay nuclei it axonally activates a specific subset of neurons within the thalamic pulvinar. Pulvinar analogically integrates this with concurrent specific inputs from the thalamic dorsomedial nucleus which itself is integrating inputs from the prefrontal cortex (goals) and the amygdaloid nuclei (moods). The pulvinar's specific integral is then axonally projected back to cortex UNDER NON-SPECIFIC BOOST from the thalamic centromedian nucleus. This ensures unitary attention focussing influenced by acquired priorities. Given that neocortex is genetically organized as a classifying mechanism, it also permits virtually limitless part-novel learning and best-match reality-testing of percepts (and concepts in humans). In schizophrenia the non-specific booster system is bilaterally blocked at the centromedian nucleus. In mania the non-specific thalamic system is shunted, at midbrain, into the non-specific direct cortical system. In melancholia both of these brainstem systems are subnormal in non-specific output. Figure 1 schematizes the main axonal circuitry. Analogical integration occurs within predominantly dendro-dendritic networks.
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PMID:Thalamic attention circuitry normal and psychotic. 652 73

The total content of zinc in the adult human body averages almost 2 g. This is approximately half the total iron content and 10 to 15 times the total body copper. In the brain, zinc is with iron, the most concentrated metal. The highest levels of zinc are found in the hippocampus in synaptic vesicles, boutons, and mossy fibers. Zinc is also found in large concentrations in the choroid layer of the retina which is an extension of the brain. Zinc plays an important role in axonal and synaptic transmission and is necessary for nucleic acid metabolism and brain tubulin growth and phosphorylation. Lack of zinc has been implicated in impaired DNA, RNA, and protein synthesis during brain development. For these reasons, deficiency of zinc during pregnancy and lactation has been shown to be related to many congenital abnormalities of the nervous system in offspring. Furthermore, in children insufficient levels of zinc have been associated with lowered learning ability, apathy, lethargy, and mental retardation. Hyperactive children may be deficient in zinc and vitamin B-6 and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of schizophrenia.
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PMID:Zinc, the brain and behavior. 708 16

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

Assuming the existence of encoding synapses which record presynaptic axonal 'on-off' patterns as the contents of memory, and the existence of modulating synapses which help encoding synapses develop long-term potentiation and depression so as to convert short-term memory into long-term memory, it is possible to outline a brain model according to neuroanatomy. The loop of memory-conversion consists of the axons connecting the perceptive cortices, mesotemporal lobes, dorsomedial nuclei of thalamus (which also receive axons from septohippocampal complex and, indirectly, fornices), and prefrontal lobes. The contents of thought, feeling, dreaming, hallucination, and delusion all result from activation of different axonal 'on-off' patterns in many sets of synapses, and retrieval of memory, reactivation of the presynaptic axonal 'on-off' patterns in the correlating sets of synapses. In this model, degenerated synapses may be responsible for the thought disorder of schizophrenia.
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PMID:A brain model with the circuit to convert short-term memory into long-term memory. 914 Aug 85

Several lines of evidence support an involvement of the anterior cingulate cortex in the pathophysiology of schizophrenia. Immunocytochemical techniques using antibodies against calcium-binding proteins permit a selective demonstration of certain subgroups of cortical GABAergic interneurons. The anterior cingulate cortex from the brains of schizophrenic patients and control subjects was studied with an antibody against parvalbumin. The immunoreactive structures were assessed qualitatively and quantitatively. Parvalbumin immunoreactivity was detected in a subpopulation of GABAergic local circuit neurons, in axonal structures (including axon cartridges) and in diffuse, band-like neuropil material. Schizophrenic anterior cingulate cortex was found to contain the same interneuron types as controls, but displayed a significant increase of parvalbumin-immunoreactive neuronal soma profiles in layers Va and Vb, whereas the total neuronal density determined in Nissl preparations showed no difference in the two groups. A higher density of parvalbumin-positive local circuit neurons may indicate an increased inhibition of projection neurons, thus altering the neuronal output pattern of the anterior cingulate cortex in schizophrenia.
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PMID:Altered distribution of parvalbumin-immunoreactive local circuit neurons in the anterior cingulate cortex of schizophrenic patients. 928 73

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

The evidence that schizophrenia may have its origins from early in life, possibly during prenatal brain development, is based primarily on a constellation of nonspecific anatomical findings and on the results of surveys of obstetrical complications and of childhood neurological and psychological adjustment. The developmental processes implicated by this evidence are uncertain, but speculation has centered around abnormalities of neuronal proliferation, migration, and connection formation. These developmental milestones are the results of complicated cellular processes involving molecular interactions between cells and between the extracellular and intracellular milieus. To understand how these abnormalities could relate to schizophrenia, it is necessary to characterize the molecular events that define the processes. In this article, we discuss the potential impact of a number of molecules that are important in the sequence of cellular events implicated in schizophrenia. In particular, we focus on molecular mechanisms related to cell proliferation, axonal outgrowth, cell migration, cell survival, synaptic regression, myelination, and developmental aspects of early adult life. These various candidate molecules regulate different aspects of cell growth and cell-cell interactions and are involved in the regulation of deoxyribonucleic acid (DNA) expression. Very few of these molecules have been studied in the schizophrenic brain.
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PMID:A candidate molecule approach to defining developmental pathology in schizophrenia. 961 27


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