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)

Abnormalities in the layer II neurons of human entorhinal cortex have been implicated in the pathophysiology of Alzheimer's disease and schizophrenia. The reported abnormalities are not homogeneously distributed throughout the entorhinal cortex, suggesting that layer II of entorhinal cortex may contain different subpopulations of neurons, each with a different susceptibility to pathological mechanisms. In order to investigate the possible heterogeneity of neurons in layer II of human entorhinal cortex, we first identified distinct subdivisions of human entorhinal cortex by adapting the cytoarchitectonic criteria for subdivisions of monkey entorhinal cortex described by Amaral et al. (J Comp Neurol 264:326, 1987). The morphology and regional distribution of distinct subpopulations of human layer II neurons were determined through the use of immunohistochemical techniques. Multipolar, stellate, and modified pyramidal neurons in the characteristic cell clusters or islands of layer II were immunoreactive for nonphosphorylated neurofilament proteins. The intensity of immunoreactivity for the nonphosphorylated neurofilament proteins gradually increased along the rostrocaudal axis of entorhinal cortex and was primarily due to a similar gradient in the density of labeled neurons per island. The calcium-binding protein calbindin D-28K was found in both pyramidal and nonpyramidal neurons in layers II and superficial III. The distribution of calbindin-immunoreactive neurons also depended upon the region of entorhinal cortex. In rostral entorhinal cortex, labeled neurons were scattered throughout the superficial layers, whereas in caudal entorhinal cortex, distinctive patches of small calbindin-immunoreactive neurons were found among the layer II islands. Another calcium-binding protein, parvalbumin, was present in nonpyramidal neurons in layers II and III that were distinct from those containing calbindin. The regional distribution of parvalbumin-positive neurons was very similar to that of the neurofilament immunoreactive neurons; in rostral entorhinal cortex very few parvalbumin-labeled neurons were present but their frequency gradually increased in the caudal direction. In addition, punctate parvalbumin immunoreactivity was frequently encountered in the location of the nonphosphorylated neurofilament protein-positive layer II islands. These findings demonstrate that layer II of human entorhinal cortex contains distinct subpopulations of neurons, that the relative density of each subpopulation differs across cytoarchitectonic regions, and that the patterns of distribution of these subpopulations are in some cases similar and in other cases complementary. This heterogeneity in the organization of layer II of human entorhinal cortex has important implications for the study of some neuropsychiatric disorders.
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PMID:Heterogeneity of layer II neurons in human entorhinal cortex. 150 May 42

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

This study was designed to examine possible anatomical changes of thalamocortical circuits in schizophrenics. Previous immunocytochemical studies have shown that parvalbumin, a calcium-binding protein, occurs in thalamocortical projection neurons, but not in GABAergic interneurons in the anteroventral thalamic nucleus (AN). Using parvalbumin-immunocytochemistry we investigated the densities of thalamocortical projection neurons in the AN of schizophrenic cases (n = 12) and controls (n = 14). The densities of all neurons in the AN were estimated by Nissl-staining. The majority of thalamocortical projection neurons in AN were identified by parvalbumin-immunoreaction. Significantly reduced densities of thalamocortical projection neurons were estimated in the right (P = 0.003) and left AN (P = 0.018) in schizophrenic subjects. The densities of all neurons in right and left AN were also diminished in schizophrenics; however, these decreases did not reach statistical significance. The reductions of parvalbumin-positive thalamocortical projection neurons were not correlated with the length of disease, this finding supporting the neurodevelopmental etiology of structural abnormalities in schizophrenia.
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PMID:Schizophrenia and anteroventral thalamic nucleus: selective decrease of parvalbumin-immunoreactive thalamocortical projection neurons. 964 46

We immunohistochemically characterised the expression of the calcium-binding protein parvalbumin in the normal human anteroventral thalamic nucleus (AVN). Two morphologically distinct neuronal populations were found to be parvalbumin-immunoreactive (PV-IR): a large population of lightly staining PV-IR neurons and a smaller population of intensely PV-IR neurons. This second type of neuron, which displayed many characteristics normally associated with GABAergic interneurons, has not previously been described in human thalamus. Thus, presumptive thalamic interneurons in the human brain can be further subtyped on the basis of immunoreactivity to parvalbumin. This may have implications for the understanding of thalamocortical function in the normal state and in dysfunctional conditions such as Wernicke-Korsakoff syndrome and schizophrenia.
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PMID:Parvalbumin-immunoreactive neurons in the human anteroventral thalamic nucleus. 1068 38

The pathophysiology of schizophrenia involves dysfunction of the dorsolateral prefrontal cortex, and this dysfunction may be related to alterations in GABA neurotransmission. Determining the causes and consequences of altered GABA neurotransmission in schizophrenia requires knowledge of which subpopulations of cortical GABA neurons are affected. The chandelier class of GABA neurons are of interest in this regard because their axon terminals form distinctive vertical arrays (termed 'cartridges') which synapse exclusively with the axon initial segments of pyramidal neurons, the principal class of cortical excitatory neurons. We evaluated the integrity of chandelier neuron cell bodies and axon cartridges in PFC areas 9 and 46 of schizophrenic subjects using immunocytochemical techniques and antibodies against parvalbumin and the GABA membrane transporter GAT-1. Schizophrenic subjects did not differ from matched control subjects in the relative density, laminar distribution or size of parvalbumin-containing neurons. In contrast, the density of GAT-1-immunoreactive chandelier neuron axon cartridges was decreased by 40% in schizophrenic subjects compared to both normal controls and subjects with other psychiatric disorders. The axon terminals of other subclasses of GABA neurons did not appear to be similarly affected. These findings suggest that disturbed GABA neurotransmission in the PFC of schizophrenic subjects may be due to a selective alteration of GAT-1 protein in the axon terminals of chandelier neurons.
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PMID:GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. 1071 53

Using polyclonal antibody against dopamine D4 receptor we investigated cortical distribution of D4 receptors, with the special emphasis on regions of the prefrontal cortex. Prefrontal cortex is regarded as a target for neuroleptic drugs, and engaged in the regulation of the psychotic effects of various substances used in the experimental modeling of schizophrenia. Western blot analysis performed on samples from the rat cingulate, parietal, piriform cortices and also striatum revealed that antibody recognized one main band of approximately 40 kD, which corresponds to the predicted molecular weight of D4 receptor protein. In immunocytochemical studies we found D4 receptor-positive neurons in all regions of prefrontal cortex (cingulate, agranular/insular and orbital cortices) and all cortical regions adjacent to prefrontal cortex, such as frontal, parietal and piriform cortex. Substantial number of D4 receptor-positive neurons has also been observed within the striatum and nucleus accumbens. In general, a clear stratification of the D4 receptor-positive neurons was observed in the cortex with the highest density seen in layers II/III and V/VI. D4 immunopositive material was also found in the dendritic processes, particularly clearly visible in the layer II/III. At the cellular level D4 receptor immunoreactivity was seen predominantly on the periphery of the cell body, but a certain population of neurons with clear cytoplasmatic localization was also identified. In addition to cortical distribution of D4 receptor-positive neurons we tried also to define types of neurons expressing D4 receptor protein. In double-labeling experiments, D4 receptor protein was found in nonphosphorylated neurofilament H-positive, calbindin-D28k-positive, as well as parvalbumin-positive cells. Since, used proteins are markers of certain populations of pyramidal neurons and GABA-ergic interneurons, respectively, our data indicate that D4 receptors are located on cortical pyramidal output neurons and their dendritic processes as well as on interneurons. Above localization indicates that D4 receptors are not only directly influencing excitability of cortical inter- and output neurons but also might be engaged in dendritic spatial and temporal integration, required for the generation of axonal messages. Additionally, our data show that D4 receptors are widely distributed throughout the cortex of rat brain, and that their cortical localization exceeds the localization of dopaminergic terminals.
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PMID:Cortical localization of dopamine D4 receptors in the rat brain--immunocytochemical study. 1089 94

Axon cartridges are the specific terminal structures of GABAergic inhibitory chandelier interneurons. Cartridges form axo-axonal synapses with local projection neurons, thus modulating the neuronal output of diverse brain areas. In order to examine the distribution of cartridges, the anterior cingulate cortices from the brains of schizophrenic patients and control persons were examined with an antibody against parvalbumin. Axon cartridges were mainly located in layers V and VI. In our study, schizophrenic patients showed a significantly higher density of axon cartridges than controls. These findings add new evidence for disturbances of the circuitry of the anterior cingulate cortex in schizophrenia implicating that there may be an elevated inhibitory influence on the cortical output of this brain region.
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PMID:Inhibitory cartridge synapses in the anterior cingulate cortex of schizophrenics. 1090 35

The effects of social isolation on prepulse inhibition of acoustic startle (PPI), electrophysiology and morphology of subicular pyramidal neurons and the densities of interneuronal sub-types in the hippocampal formation were examined. Wistar rats (male weanlings) were housed socially (socials, n=8) or individually (isolates, n=7). When tested eight weeks later, PPI was lower in isolates. Rats then received terminal anaesthesia before slices of hippocampal formation were made in which the electrophysiological properties of a total of 108 subicular neurons were characterized. There were no differences in neuronal sub-types recorded in socials compared with isolates. Intrinsically burst-firing and regular spiking pyramidal neurons were examined in detail. There were no differences in resting membrane potential or input resistance in isolates compared with socials but action potential height was reduced and action potential threshold raised in isolates. A limited morphological examination of Neurobiotin-filled intrinsically burst-firing neurons did not reveal differences in cell-body area or in number of primary dendrites. Sections from the contralateral hemispheres of the same rats were stained with antibodies to calretinin, parvalbumin and the neuronal isoform of nitric oxide synthase (nNOS). In isolates, the density of calretinin positive neurons was increased in the dentate gyrus but unchanged in areas CA3, CA1 and subiculum. Parvalbumin and nNOS positive neuronal densities were unchanged. Hence in rats with environmentally induced reductions in PPI there are structural and functional abnormalities in the hippocampal formation. If the reduction in PPI stems from these abnormalities, and reduced PPI in rats is relevant to schizophrenia, then drugs that correct the reported electrophysiological changes might have antipsychotic effects.
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PMID:Structural and functional abnormalities of the hippocampal formation in rats with environmentally induced reductions in prepulse inhibition of acoustic startle. 1124 47

Recent studies have provided evidence for a deficit of GABA-containing interneurons in the frontal cortex in schizophrenia. That this deficit might be brought about during early foetal or neonatal life is a hypothesis consistent with the substantial indications for a neurodevelopmental aetiology of the disease. GABAergic neurons can be defined by the presence of one of three types of calcium binding proteins, which are thought to have neuroprotective properties. We have undertaken an investigation into the postnatal ontology of these neuronal subtypes and find that calretinin expression is relatively constant and present from before birth, calbindin expression is also present early but redistributes in the cortex over the first months of life, while parvalbumin-immunoreactivity is not observed until between 3 and 6 months of age. Investigation of frontal cortical tissue taken post mortem from a series of schizophrenic patients and matched control subjects revealed that parvalbumin-, but not calretinin-immunoreactive cells are significantly diminished in schizophrenia. These observations support the hypothesis that GABAergic deficits in schizophrenia may stem from toxic events occurring during cortical development which selectively target immature neurons before protection by parvalbumin is conferred.
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PMID:GABAergic neuronal subtypes in the human frontal cortex--development and deficits in schizophrenia. 1147 May 57

Deficits in a variety of different neurochemical species are consistent with a loss of cortical gamma-aminobutyric acid (GABA)ergic interneurons in schizophrenia. As well as neurochemical markers that indicate all neurons using GABA as a transmitter, and which include GABA uptake sites and glutamate decarboxylase, deficits of certain neuropeptides and calcium binding proteins coexisting with GABA have been reported. These abnormalities are indicative of losses specific to certain subtypes of GABAergic neurons. The calcium binding proteins in particular demonstrate selective deficits; we find losses of parvalbumin- and calbindin-, but not calretinin-immunoreactive cells in the prefrontal cortex in schizophrenia. These selective reductions in the density of parvalbumin- and calbindin-containing neurons could reflect functional loss of expression in intact cells or alternatively a deficit in the density of certain GABAergic neuronal subtypes. The latter interpretation is consistent with a neurodevelopmental pathogenesis involving neuronal damage at a time prior to the expression of these protective calcium-binding proteins. In this review we discuss the evidence for altered GABAergic transmission in schizophrenia.
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PMID:Neurochemical correlates of cortical GABAergic deficits in schizophrenia: selective losses of calcium binding protein immunoreactivity. 1157 54


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