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)

To investigate whether volume reduction of the hippocampal formation of schizophrenics, as described previously, is paralleled by loss of neurons and fibre systems, tissue volumes and cell numbers of all parts of the hippocampal formation in post mortem brains of 13 schizophrenics and 11 age-matched controls belonging to the Vogt collection were determined. Volumes of the whole hippocampal formation (P less than 0.01), the whole pyramidal band (P less than 0.001) and the hippocampal segments CA1/CA2 (P less than 0.01), CA3 (P less than 0.005), CA4 (P less than 0.01) were decreased, whereas no significant volume reduction of the alveus and fimbria hippocampi and prosubiculum/subiculum could be found. The perforant path showed a trend towards volume reduction (P less than 0.1). The absolute number of pyramidal cells (tissue volume X cell density) was diminished in CA1/CA2 (P less than 0.05), CA3 (P less than 0.05) and CA4 (P less than 0.05), but was not significantly changed in the prosubiculum/subiculum, the presubiculum/parasubiculum and the granular cell layer of the dentate fascia. Pyramidal cell loss in CA1/CA2, CA3, CA4 was more distinct in the paranoid patients than in catatonics. The findings are discussed with respect to current hypotheses of limbic dysfunction in schizophrenia.
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PMID:Cell loss in the hippocampus of schizophrenics. 380 99

Epidemiological studies point to an association between prenatal exposure to influenza and later schizophrenia. Such studies are consistent with neuropathologic reports demonstrating cytoarchitectural abnormalities in the hippocampus and parahippocampal gyrus suggestive of second trimester developmental anomalies. The hypothesis that prenatal exposure to influenza in the second trimester may induce hippocampal pyramidal cell disarray in mice was investigated. Between days 9-16 of pregnancy, 35 Balb/c mice were intranasally inoculated with either a mouse-adapted or non mouse-adapted pool of Influenza A/Singapore/1/57 (H2N2), and 10 controls were inoculated with normal saline. Offspring were sacrificed on day 21 postpartum. Microscopic examination of the CA1-CA2 junctional areas in the offspring of mice exposed to influenza failed to demonstrate excess pyramidal cell disarray when compared with influenza-free, age matched controls. There was evidence that disarray was greater among those exposed on day 13 of pregnancy. Analyses of the data by sex and severity of maternal infection failed to reveal any significant effects.
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PMID:Does prenatal exposure to influenza in mice induce pyramidal cell disarray in the dorsal hippocampus? 899 77

The clinical histories of 102 schizophrenics who died at 70 years of age or older were reviewed. The incidence of neurofibrillary tangles (NFTs) was two times higher in the patients who received (74%) than in those who did not receive (36%) treatment with neuroleptics. The development of NFTs started earlier in the treated group. Further studies comparing brains of nine schizophrenics (average age, 86 years) who did not receive treatment with neuroleptics and seven age-matched cases who received neuroleptics, both with neurofibrillary pathology and neuritic plaques, showed characteristic differences. The numerical density of NFTs was slightly greater in the cornu Ammonis (CA1 and CA2) and subiculum of treated patients. Significantly lower numerical density and lower percentage of pretangles (stage 0) and early and mature tangles (stages 1 and 2) and increased number of end-stage tangles (stage 3) were found in the CA, subicular complex, and cerebral cortex of the treated group. These changes suggest accelerated neurofibrillary degeneration in neurons. A significant increase in the numerical density of tau-1-positive plaques was observed in sector CA1 of the CA (from 0.15/mm2 to 17.36/mm2), subiculum (from 0/mm2 to 16.62/mm2), temporal cortex (from 0.14/mm2 to 9.46/mm2), and occipital cortex (from 0.08/mm2 to 0.39/mm2). The higher numerical density of tau-1-positive plaques, but not of 4G8-positive plaques, indicates acceleration of neurofibrillary changes in the plaques of patients treated with neuroleptics. The significant decrease (20-25%) in the numerical density of neurons in the pyramidal layer of sectors 2-4 in the CA appears to be associated with accelerated neurofibrillary changes in neurons and plaques in the treated group. This study demonstrates that chronic treatment with neuroleptics--not schizophrenia itself--significantly increases the risk of more frequent, earlier, and accelerated development of neurofibrillary pathology in the brains of elderly schizophrenics.
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PMID:Neurofibrillary pathology in brains of elderly schizophrenics treated with neuroleptics. 788 52

Recent postmortem studies have demonstrated subtle alterations in the hippocampal formation (HIPP) of patients with schizophrenia (SZ). These changes include a decreased density of nonpyramidal neurons (NPs), an increase of the GABAA, but not benzodiazepine receptors and a neuroleptic-dose-related increase of GAD65-IR terminals, particularly in sectors CA3 and CA2. High resolution studies of the GABAA receptor have further suggested that a decrease of disinhibitory GABAergic activity (i.e., GABA-to-GABA) in stratum pyramidale of CA3 may coexist with reduced inhibitory modulation (i.e., GABA-to-excitatory pyramidal neuron) in the stratum oriens of this same sector. These changes could potentially involve excitotoxic damage to interneurons in CA2; but, the precise time frame for the induction of such an injury during pre- versus postnatal life cannot as yet be inferred from the available data. These findings are consistent with reports of abnormal oscillatory rhythms and increased basal metabolic activity in the HIPP of patients with SZ. The fact that patients with manic depression also show a decrease of NPs in CA2 suggests that changes in the GABA system may not be related to a susceptibility gene for SZ. Rather, these alterations could be associated with a nonspecific factor, such as stress, experienced either early in life or much later during adolescence or adulthood. Presumably, there are also changes associated in other transmitter systems that may play a more specific role in establishing the SZ phenotype.
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PMID:Evidence for altered trisynaptic circuitry in schizophrenic hippocampus. 1047 13

The density of TH-IR varicosities was analyzed in the hippocampus of 15 normal controls and 11 schizophrenics. The average density of varicosities in apposition with pyramidal cells and in the neuropil was 30-35% lower in CA2, but not other sectors of schizophrenics. Age was correlated with varicosity density in all sectors, particularly in CA2 where young patients showed a 50% reduction on non-pyramidal cells. Neuroleptic dose showed a negative correlation with the density of varicosities, and notably the dose of young schizophrenics was four times higher than that of older subjects. Thus, antipsychotic dose appears to be associated with a suppression of a normal age-related increase of dopamine projections to CA2 during the early phases of schizophrenia.
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PMID:Effect of age and neuroleptics on tyrosine hydroxylase-IR in sector CA2 of schizophrenic brain. 1061 38

Microtubule associated proteins (MAPs) are central to the development of normal neuronal cytoarchitecture and have been reported to be altered in schizophrenia. In 12 schizophrenic (DSM-III-R criteria) and 12 control hippocampi, we estimated the MAP2 immunoreactive dendritic length using antibodies that recognize total MAP2 (MAP2-T), and a non-phosphorylated form of MAP2 (MAP2-NP). Within the corona ammonis (CA) subregions, and the subiculum, we estimated, for each antibody, the length of the immunoreactive dendritic arborisation using a stereological length estimation technique based on Bouffon's Needle principle and image analysis computer software. Controlling for the confounding effects of age and post-mortem delay, we have found an elevation in overall MAP2-NP immunoreactive dendritic length among schizophrenic subjects in the CA3 (F=5.9, p=0.03), CA2 (F=6.5, p=0.02), CA1 (F=8.3, p=0.01) and subicular (F=9.5, p=0.008) hippocampal subregions. Similar analyses of MAP2-T immunoreactive dendritic length demonstrated significant elevations in the CA1 (F=8.3, p=0.02), CA4 (F=4.9, p=0.04) and subicular (F=7.4, p=0.01) regions. The findings of this quantitative study of increased MAP2 immunoreactive dendritic arborisation in schizophrenia are most likely to reflect either an altered dendritic arborisation or a generalised increase in levels of MAP2 with the hippocampal pyramidal neurons. These findings add to the growing literature indicating the presence of synaptodendritic abnormalities in schizophrenia.
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PMID:Increased dendritic MAP2 expression in the hippocampus in schizophrenia. 1070 40

Recent studies have demonstrated the involvements of gamma-aminobutyric acid (GABA) neurotransmitter systems in the schizophrenic brain. In order to further elucidate the alterations of this system in schizophrenia, we employed immunohistochemical techniques and examined the expression and anatomical distribution of the GABA(B) receptor in the hippocampus of five subjects with schizophrenia and three age-matched controls. In the control hippocampus, the most intense immunoreactivity was observed in the soma and processes of multipolar interneurons throughout the hippocampus. Pyramidal cells too were intensely labeled in their soma and proximal portion of dendrites, although the labeling intensity was varied in each subregion. For example, in the CA1 subfield, the labeling intensity of pyramidal cells was much less intense than that in the CA3 and CA2 subfields. In the subjects with schizophrenia, GABA(B) immunoreactivity was markedly reduced in granule cells as well as in pyramidal cells throughout the CA fields. In interneurons, GABA(B) labeling was relatively preserved compared to that in pyramidal cells. Our findings suggest that in the hippocampus of schizophrenic patients the expression of the GABA(B) receptor is reduced, and raise the possibility that this reduction contributes to the pathophysiological process in the schizophrenic brain.
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PMID:Immunohistochemical localization of gamma-aminobutyric acid(B) receptor in the hippocampus of subjects with schizophrenia. 1073 85

We investigated the effect of 10 months ovariectomy and a correction therapy, 2 weeks before the rats were killed, of oestradiol, progesterone or their combination on NMDA and AMPA receptor binding in the hippocampus, dentate gyrus, striatum, nucleus accumbens and frontal cortex of the rat brain as well as on amino acid levels in frontal cortex. NMDA and AMPA binding densities were assayed by autoradiography using, respectively, L-[3H]glutamate and [3H]AMPA; amino acid concentrations were measured by high performance liquid chromatograhy (HPLC) coupled with UV detection. Ovariectomy was without effect on NMDA and AMPA binding density in all brain regions assayed except in the hippocampal CA1 region and dentate gyrus where it decreased NMDA binding density compared to intact rats values. Oestradiol restored and increased NMDA binding density in the CA1 subfield and the dentate gyrus of ovariectomized rats but, by contrast, it decreased binding density in the striatum and in the frontal cortex while having no effect in the CA2/3 subfield of the hippocampus and in the nucleus accumbens. Oestradiol was without effect on AMPA binding density in the hippocampus and the dentate gyrus but it reduced AMPA binding density in the striatum, the frontal cortex and the nucleus accumbens. Progesterone, and oestradiol combined with progesterone, decreased NMDA but not AMPA binding density in the frontal cortex of ovariectomized rats, and they were without effect on these receptors in the other brain regions assayed. Amino acid concentrations in the frontal cortex were unchanged after ovariectomy or steroid treatments. The effect of oestradiol in the hippocampus confirmed in the present study and our novel findings in the frontal cortex, striatum and nucleus accumbens may have functional significance for schizophrenia and neurodegenerative diseases.
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PMID:Regional and selective effects of oestradiol and progesterone on NMDA and AMPA receptors in the rat brain. 1079 84

This chapter reviews recent postmortem studies of schizophrenic brain and discusses the potential role of the amygdala in the induction of hippocampal abnormalities in this disorder. Based on available evidence, sectors CA4, CA3, and CA2, but not CA1, show preferential changes in schizophrenic subjects, although the most pronounced changes have been found in CA3 and CA2. It seems likely that the amygdala would contribute in some way to the induction of abnormalities along the trisynaptic pathway via its direct input to sectors CA3 and CA2, as well as an indirect one that involves the entorhinal cortex and its perforant path projection to the area dentata. The postmortem findings reported to date have been integrated into a working model in which decreases of inhibitory GABAergic modulation are invoked to explain the observation from a recent PET scan study (Heckers et al., 1999) that baseline metabolic activity in the hippocampus of schizophrenics is increased. In addition, however, the apparent inability of schizophrenics to increase metabolic activity in the hippocampus when challenged with a memory retrieval task may reflect a disturbance of disinhibitory modulation postulated herein to occur in sector CA3, a key relay point along the trisynaptic pathway. Overall, it seems plausible that an increase of excitatory activity entering the hippocampus from the basolateral complex via both direct and indirect pathways may make a significant contribution to the pathophysiology of schizophrenia.
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PMID:Amygdalo-entorhinal inputs to the hippocampal formation in relation to schizophrenia. 1091 81

Recent biochemical observations have suggested the abnormalities in the gamma-amino-butyric acid (GABA)ergic system in schizophrenic brains. In the present study, we investigated the subunits gene expressions and ligand binding of the GABA(A) receptor following acute and chronic administration of phencyclidine (PCP), which induces schizophrenia-like symptoms, in rats using in situ hybridization and in vitro quantitative autoradiography. PCP i.p. administration at a daily dose of 7.5 mg/kg resulted in a significant decrease in expression of alpha 1 subunit mRNA in cerebral cortices (cingulate (-13%) and temporal cortex (-6%)) and hippocampal formation (CA1 (-11%), CA2 (-10%), CA3 (-11%) and dentate gyrus (-12%)) 1 h after a single treatment. In the repeated PCP administrations for 14 days, the expression of beta 2 mRNA in the cerebellum (-10%) and of beta 3 mRNA in the cerebral cortices (cingulate (-12%), parietal (-16%) and temporal cortex (-16%), caudate putamen (-18%), inferior colliculus (-18%), and cerebellum (-15%) were significantly decreased. In addition, [(35)S]t-butylbicyclophosphorothionate (TBPS) binding was also reduced in layer IV of the frontoparietal cortex (-14%), inferior colliculus (-17%), and cerebellum (-12%) following chronic PCP treatment, while no changes were observed following acute PCP treatment. These results indicate that single and repeated administrations of PCP independently regulate the expression of GABA(A)/benzodiazepine (BZD) receptor subunits mRNA and its receptor binding in the brain.
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PMID:Differential expression of GABA(A) receptor subunit mRNAs and ligand binding sites in rat brain following phencyclidine administration. 1094 Nov 40


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