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)

Cells from the olfactory epithelium of adult human cadavers have been propagated in primary culture and subsequently cloned. These cells exhibit neuronal properties including: neuron-specific enolase, olfactory marker protein, neurofilaments, and growth-associated protein 43. Simultaneously, the cells exhibit nonneuronal properties such as glial fibrillary acidic protein and keratin, the latter suggesting properties of neuroblasts or stem cells. These clonal cultures contain 5-10% of cells sufficiently differentiated to show odorant-dependent cyclic adenosine 3',5'-monophosphate (cAMP) or calcium-release responses when challenged with submicromolar concentrations of odorants. The potential of culturing neuronal cells from patients with neuropsychiatric disorders, such as Alzheimer's disease or schizophrenia, could enable the study of the pathophysiology of these neurons in the culture dish and allow new approaches to the study of mental illness.
J Mol Neurosci 1992
PMID:Continuous culture of neuronal cells from adult human olfactory epithelium. 132 Sep 21

Total cellular polyadenylated RNA (poly(A)+ RNA, mRNA) was prepared after guanidinium thiocyanate extraction of frozen brain tissue from age-matched controls and patients suffering from schizophrenia and unipolar depression. These mRNA populations were analysed by in vitro translation followed by two-dimensional gel analysis. Data were obtained from fluorograms derived from 10 different schizophrenic patients, 10 different controls and 5 different depressive patients. The relative concentrations of mRNA species coding for 4 translation products (33 kDa, pI 5.8; 26 kDa, pI 5.8; 35 kDa, pI 7.1; 23 kDa, pI 6.1) were significantly reduced in schizophrenia compared to controls when determined by computerised image analysis of the fluorograms. In the case of depression, the relative concentrations of mRNA species coding for 6 translation products were significantly altered, 4 being increased (38 kDa, pI 6.2, 17 kDa, pI 5.7, 35 kDa, pI 7.1; 23 kDa, pI 6.1) and two decreased (34 kDa, pI 6.2; 33 kDa, pI 5.8). Three translation products were altered in both schizophrenia and depression, one (33 kDa, pI 5.8) being altered according to the same trend, a decrease relative to controls, but two (35 kDa, pI 7.1; 23 kDa, pI 6.1) being altered differently in schizophrenia (reduced) and depression (increased). The effects of post mortem delay, mode of death and drug treatment on mRNA composition were also examined and found not to affect the levels of these translation products significantly. The significance of these changes will be discussed in relation to their relevance of biological mechanisms in the psychoses.
Brain Res Mol Brain Res 1992 Jan
PMID:Changes in relative levels of specific brain mRNA species associated with schizophrenia and depression. 137 64

Risperidone and ocaperidone are new benzisoxazol antipsychotics with particularly beneficial effects in schizophrenia. We report a comprehensive study on the in vitro and in vivo receptor binding profile of the new compounds, compared with haloperidol, and on the drug effects on monoamine and metabolite levels in various brain areas. The in vitro receptor binding and monoamine uptake inhibition profiles, comprising 29 receptors and four monoamine uptake systems, revealed that ocaperidone and risperidone bound primarily, and with the highest affinity thus far reported, to serotonin 5HT2 receptors (Ki values of 0.14 and 0.12 nM, respectively). Further, the drugs bound at nanomolar concentrations to the following receptors (Ki values, in nM, for ocaperidone and risperidone, respectively): alpha 1-adrenergic (0.46 and 0.81), dopamine D2 (0.75 and 3.0), histamine H1 (1.6 and 2.1), and alpha 2-adrenergic (5.4 and 7.3). In contrast, haloperidol showed nanomolar affinity for D2 receptors (1.55) and haloperidol-sensitive sigma sites (0.84) only. The in vitro binding affinity of ocaperidone, risperidone, and haloperidol for D2 receptors was exactly the same when measured in membranes from rat striatum, nucleus accumbens, tuberculum olfactorium, and human kidney cells expressing the cloned human D2 receptor (long form). In vivo binding in rats, using intravenous administration of [3H]spiperone, revealed very potent occupation by ocaperidone and risperidone of 5HT2 receptors in the frontal cortex (ED50 of 0.04-0.03 mg/kg); in this respect, they were 6, 30, and 100 times more potent than ritanserin, haloperidol, and clozapine, respectively. Ocaperidone occupied D2 receptors in the striatum and the nucleus accumbens with similar potency as did haloperidol (ED50 of 0.14-0.16 mg/kg). Risperidone revealed biphasic inhibition curves in the latter brain areas, indicating that [3H] spiperone labeled both 5HT2 receptors (occupied by risperidone at less than 0.04 mg/kg) and D2 receptors (risperidone ED50 of approximately 1 mg/kg). In the tuberculum olfactorium, 5HT2 and D2 receptors were also distinguished with risperidone. The ED50 values for occupation of the latter were for ocaperidone and risperidone 2 times lower and for haloperidol 2 times higher than in the striatum. Ocaperidone, risperidone, and haloperidol readily increased the levels of the dopamine metabolites 3,4-dihydroxybenzene acetic acid and homovanillic acid in the striatum, the nucleus accumbens, the tuberculum olfactorium, and, to some extent, the frontal cortex. Dose-response curve shapes were markedly different; with ocaperidone maximal levels were reached at 0.16 mg/kg and maintained to 10 mg/kg; with risperidone the levels tended to increase continuously up to 10 mg/kg. Haloperidol produced dome-shaped curves (maximum at 0.16-0.63 mg/kg).(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Pharmacol 1992 Mar
PMID:In vitro and in vivo receptor binding and effects on monoamine turnover in rat brain regions of the novel antipsychotics risperidone and ocaperidone. 137 84

An experimental method to test the hypothesis that antipsychotic (neuroleptic) agents influence gene expression in the mouse brain has been developed using the cis and trans stereoisomers of flupenthixol. The cis form of the drug is known to be clinically effective against some of the psychotic symptoms of schizophrenia as opposed to the trans isomer which is relatively inactive. A 2- to 3-fold increase in the abundance of dopamine 2 receptor mRNA was observed in the cis treated mice after a period of ten weeks. No change was observed in the expression of the dopamine D2 receptor gene upon treatment with the trans isomer. No change in the amount of 5-HT1A, 5-HT1C, alpha 1 adrenergic, beta 1 and beta 2 adrenergic neuroreceptor mRNA was found in the mice treated with active drug. The results show a long-term adaptation to D2 antagonism at the level of gene expression which occurs over a similar time scale to that of the clinical response to neuroleptic treatment of schizophrenia.
Brain Res Mol Brain Res 1991 May
PMID:Stereospecific effect of flupenthixol on neuroreceptor gene expression. 164 66

Complementary oligonucleotide probes specific for the human pro-opiomelanocortin (POMC) mRNA were used to analyze the expression of POMC gene in 56 human postmortem pituitaries by in situ hybridization histochemistry. POMC transcripts were visualized by autoradiography in anterior lobe of the pituitary where their distribution was in a 'patchy-like' pattern. No hybridization could be observed in the posterior lobe of the pituitary. We examined pituitaries from several controls and from patients dying with schizophrenia, Parkinson's disease. Alzheimer's disease, Wernicke's encephalopathy and depressive illness. Computer-assisted microdensitometric semiquantification of POMC mRNA using a complementary oligonucleotide as hybridization standard, revealed no statistically significant effect of postmortem delay (between 2.5 and 66 h), of gender, age (between 22 and 103) or cause of death in 56 human pituitary glands. A large variation in POMC levels was already observed among all 30 control cases. The levels of POMC mRNA observed in pituitaries from different pathologies did not show a significant variation when compared with control cases.
Brain Res Mol Brain Res 1991 May
PMID:Study of pro-opiomelanocortin mRNA expression in human postmortem pituitaries. 171 87

This paper reviews a recent body of evidence from computed tomography, imaging methods, and neuropsychological testing, emphasizing schizophrenia. The review indicates important characteristics of this disorder that can be conceptualized as similar to neurological disorders, and that have a probable neuropathologic basis. Although the argument is compelling in many respects, cautionary observations are also discussed, and a need for positioning subgroups based on neurological etiology is advanced. This serves as an introduction to a discussion of neurological diseases as potential models for psychiatric disorders.
Mol Chem Neuropathol 1990 Mar
PMID:Current conceptualizations of psychiatric illnesses as neurological disorders. 214 27

1. A review of the effects of long-term administration of antidepressants and neuroleptics on receptors in the central nervous system is presented. 2. The effects of antidepressants on adenylate cyclase activity and on receptor binding in brain tissue are discussed. Effects on a variety of receptor types are considered. 3. The utilization of electrophysiological, behavioral, and neurochemical studies to assess receptor function after chronic antidepressant administration is discussed, as is the use of peripheral receptor estimations in clinical studies. 4. Animal studies on the actions of chronic administration of neuroleptics on pre- and postsynaptic dopamine receptors are reviewed. Effects of these drugs on dopamine receptors in humans are considered from the following perspectives: postmortem and in vivo binding studies in schizophrenia, tardive dyskinesia, and central versus peripheral receptor estimation.
Cell Mol Neurobiol 1989 Mar
PMID:Effects of long-term administration of antidepressants and neuroleptics on receptors in the central nervous system. 256 69

The aim of this study was to determine the effect of repeated electroconvulsive stimulation (ECS) on the expression of neuropeptide Y (NPY) and somatostatin (SS) mRNA in the rat brain. For that purpose, quantitative in situ hybridization histochemistry and RNA blot analysis were used. In the hippocampal formation the prevalence of NPY mRNA positive neurons increased in the hilus of the dentate gyrus and the CA3 while a decrease was seen in layers II-III of the entorhinal cortex. In contrast, SS mRNA was increased in the granule cells of the dentate gyrus and in most neurons of the outer parts of the layer III in the entorhinal cortex with cell bodies of perforant pathway projections to the hippocampal CA1 region. Both NPY and SS mRNA expressing neurons were increased in numerical density in the prefrontal cortex with similar amounts of mRNA in individual NPY positive neurons after the stimulations while SS mRNA levels decreased in hybridization positive neurons. In the striatum the only observed significant effect was an increased prevalence of NPY mRNA positive neurons in the caudal nucleus accumbens. Our results provide an outline of a complex functional anatomy of ECS in the rat brain. This type of investigations contributes to map the neuronal systems involved in the action of ECT used in the treatment of affective and schizophrenic disorders.
Brain Res Mol Brain Res 1995 Jul
PMID:Limbic effects of repeated electroconvulsive stimulation on neuropeptide Y and somatostatin mRNA expression in the rat brain. 747 35

Several lines of anatomical, neurochemical, electrophysiological, and behavioral evidence suggest the existence of physiological interactions between neurotensin (NT) and the brain dopaminergic systems. Thus, NT has been shown to exert a neuroleptic-like action and could be implicated in the pathogenesis and treatment of schizophrenia. It is thus of particular importance to develop in vitro cell culture systems as models to study such interactions. Rat adrenal pheochromocytoma PC12 cells, which expressed high levels of tyrosine hydroxylase, were used in the present study. In contrast to rat brain cells in primary cultures, PC12 cells did not express functional NT receptors. However, they were able to express both NTmRNA and NT in response to NGF, forskolin, and dexamethasone. Those neurochemical modifications furthermore may be related to changes in the morphology of the PC12 cells in response to NGF, forskolin, and dexamethasone alone or in combination. These data suggest that PC12 cells may provide a useful model to study in vitro the regulation of both catecholamine and neurotensin phenotypes.
Mol Neurobiol
PMID:Treatment of PC12 cells by nerve growth factor, dexamethasone, and forskolin. Effects on cell morphology and expression of neurotensin and tyrosine hydroxylase. 757 2

Schizophrenia is associated with a complex pattern of alterations in the glutamatergic system of the brain. Previous studies have shown a reduced density of some hippocampal non-N-methyl-D-aspartate (non-NMDA) receptors which is accompanied by a loss of encoding receptor mRNA. We have extended this work using in situ hybridization histochemistry with oligonucleotide probes specific for two non-NMDA receptor transcripts, GluR1 and GluR2, in right and left medial temporal lobe sections from 9 schizophrenics and 14 matched normal controls. Both mRNAs were found to be decreased bilaterally and to a similar degree in the hippocampal formation in schizophrenia. Analysis of autoradiograms showed a regional loss of GluR1 and GluR2 mRNAs in dentate gyrus, CA4, CA3 and subiculum. GluR2 mRNA was also reduced in parahippocampal gyrus. These reductions ranged from 25% to 70% in terms of 35S nCi/g tissue equivalents. Additionally we measured grain density for the mRNAs over individual pyramidal neurons in each area. GluR1 and GluR2 mRNAs were less abundant per neuron in CA4 and CA3 in schizophrenia than in controls. GluR2 mRNA was also reduced significantly in parahippocampal gyrus neurons, with an increase in the proportion of GluR1 mRNA to GluR2 mRNA in this cell population. No asymmetries in expression of GluR1 and GluR2 were found in normal or schizophrenic brains. These data further the evidence for reduced non-NMDA receptor expression in the medial temporal lobe in schizophrenia. They confirm the decrease in GluR1 mRNA and show that there are similar losses of GluR2 mRNA in the hippocampal formation. The pattern of changes in the two mRNAs suggests a common mechanism which is unknown but which may be a correlate of the neurodevelopmental abnormalities postulated to underlie the disease. The reduction of GluR2 mRNA but not GluR1 mRNA in parahippocampal gyrus neurons in schizophrenia may have functional consequences given the calcium permeability of non-NMDA receptors lacking the GluR2 subunit.
Brain Res Mol Brain Res 1995 Apr
PMID:Decreased expression of mRNAs encoding non-NMDA glutamate receptors GluR1 and GluR2 in medial temporal lobe neurons in schizophrenia. 760 9


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