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)

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.
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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

Many investigations suggest that abnormalities of the immune system are involved in the pathophysiology of schizophrenia. We recently found increased activity of leukocyte elastase (LE) and elevated levels of autoantibodies to neurospecific protein - nerve growth factor (Aab to NGF) - products of the innate and adaptive arms of the immune system in the serum of patients with acute stage schizophrenia. The aim of this study is to elucidate whether or not the changes of LE activity and Aab to NGF level are related to prominent features of schizophrenia. Patients (n=71) corresponding to ICD-10 criteria for relapse-remitting schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS). Patients with predominantly positive symptoms showed significantly elevated serum levels of Aab to NGF compared to patients with predominantly negative symptoms, who were more likely to exhibit the high LE activity. Moreover, progression of positive symptoms was coupled with gradual increase of Aab to NGF level and reduction of LE activity. Based on these findings we conclude that the high levels of Aab to NGF relate to a clinical picture characterised mainly by positive symptoms of schizophrenia, whereas high LE-activities relate to a clinical picture with mainly negative symptoms of schizophrenia.
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PMID:Leukocyte elastase and autoantibodies to nerve growth factor in the acute phase of schizophrenia and their relationship to symptomatology. 1534 38

Some studies in animal models showed that several neurotrophins may be implicated in the regulation of light-dependent suprachiasmatic pacemaker and in other functions implicated in long-term memory acquisition during sleep. However, no data are known about the role played by NGF in ultradian regulation in humans. The aim of this study was to investigate whether or not there is a natural diurnal fluctuation during daytime in healthy and schizophrenic subjects with a normal light/dark cycle. In a sample of 33 subjects (10 male schizophrenics and 23 healthy subjects) an ELISA assay was used to study the ultradian NGF cycle in blood samples at 9.00, 13.00 and 20.00 hours. The study showed an ultradian rhythm of NGF in healthy subjects with a "V" trend: higher at 9:00 and 20:00 and lower at 13:00. We also show significant differences between male and female controls. No NGF ultradian rhythm among schizophrenic patients compared to healthy subjects was found. The results of this study lead to a rhythmic NGF regulation that appears altered in schizophrenics, where higher levels in the morning and lower levels in the evening were observed, compared to the controls, and support the hypothesis of a role played by NGF in schizophrenia.
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PMID:Ultradian variation of nerve growth factor plasma levels in healthy and schizophrenic subjects. 1546 70

Indices of congenital leukocyte elastase (LE) activity and adaptive immunity (a level of autoantiboies to nerve growth factor--AabNGF) in blood serum of patients with schizophrenia (attack-like, continuous and slow progressive types) and schizoaffective psychosis have been compared with clinical presentations of the disorders. A patient's state was assessed by clinico-psychopathological methods and with the Positive and Negative Syndromes Scale (PANSS). All schizophrenia types and schizoaffective psychosis were accompanied by LE activity elevation. An increase of AabNGF level was observed only in attack like and continuous schizophrenia. Correlations between AabNGF level and negative symptoms evaluated, using the PANSS, suggest a relation of autoimmune reactions against NGF to the progression of schizophrenic process. Differences in AabNGF level between schizoaffective psychosis and attack-like schizophrenia confirm nosologic independence of schizoaffective psychosis and demand for additional differential laboratory diagnosis of these disorders.
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PMID:[Some indices of congenital and acquired immunity in patients with endogenous diseases of schizophrenic spectrum disorders]. 1595 12

Schizophrenia may be related to immunity as is suggested by many findings of altered immune parameters in schizophrenic patients. How immune alterations might be involved in the emergence of psychosis is still unclear. Clearly, however, the dopamine hypothesis has been confirmed in recent studies, which implies a crucial role for dopamine and the dopamine D2 receptor (D2R) within the pathogenesis of schizophrenia. The Dopamine D3 receptor (D3R) is considered to have autoreceptor properties modulating the synthesis and release of dopamine, thereby possibly antagonizing the dopamine D2-receptor-mediated effects of dopamine and has been found reduced in schizophrenic patients during acute psychosis and increasing in the advent of negative schizophrenic symptoms. Immune parameters apparently influence the expression of dopamine receptors by means of their capability to induce regulatory factors involved in the expression of dopamine receptor subtypes, such as the neurotrophins, associations of which with psychosis have been reported repeatedly. Here, we propose a hypothesis of immune alterations that influence the production of distinct neurotrophins such as BDNF and NGF that, as animal studies suggest, influence the expression of dopamine receptor subtypes. This mechanism could result in a decrease of D3R and a consecutive relative preponderance of D2R and thereby connect immune alterations and schizophrenia.
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PMID:Dopamine D3 receptor and schizophrenia: a widened scope for the immune hypothesis. 1654 Feb 54

A balanced chromosomal translocation, segregating with mental illnesses in a large Scottish family, interrupts the disrupted-in-schizophrenia 1 (DISC1) gene, which would result in loss of DISC1 function via haploinsufficiency or dominant-negative effects (or possibly could cause gain-of-function effects) if a truncated protein is present. To evaluate the effects of a predicted protein, mutant DISC1, we generated stable PC12 cell clones with inducible expression of mutant or full-length human DISC1 (hDISC1). Our study presents new observations that the inhibitory effects of mutant hDISC1 on NGF-induced neurite outgrowth are dependent on the level and timing of expression of mutant DISC1 and the concentrations of NGF, and are associated with altered sub-cellular distribution of endogenous DISC1 and ATF4, and decreased protein levels of LIS1. Thus, inducible expression of DISC1 in PC12 cell clones is a valuable in vitro model for further studying the molecular mechanisms likely due to loss of function of DISC1 relevant to the pathogenesis of major mental illnesses.
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PMID:PC12 cell model of inducible expression of mutant DISC1: new evidence for a dominant-negative mechanism of abnormal neuronal differentiation. 1741 9

Amphetamines (methamphetamine and d-amphetamine) are dopaminergic and noradrenergic agonists and are highly addictive drugs with neurotoxic effect on the brain. In human subjects, it has also been observed that amphetamine causes psychosis resembling positive symptoms of schizophrenia. Neurotrophins are molecules involved in neuronal survival and plasticity and protect neurons against (BDNF) are the most abundant neurotrophins in the central nervous system (CNS) and are important survival factors for cholinergic and dopaminergic neurons. Interestingly, it has been proposed that deficits in the production or utilization of neurotrophins participate in the pathogenesis of schizophrenia. In this study in order to investigate the mechanism of amphetamine-induced neurotoxicity and further elucidate the role of neurotrophins in the pathogenesis of schizophrenia we administered intraperitoneally d-amphetamine for 8 days to rats and measured the levels of neurotrophins NGF and BDNF in selected brain regions by ELISA. Amphetamine reduced NGF levels in the hippocampus, occipital cortex and hypothalamus and of BDNF in the occipital cortex and hypothalamus. Thus the present data indicate that chronic amphetamine can reduce the levels of NGF and BDNF in selected brain regions. This reduction may account for some of the effects of amphetamine in the CNS neurons and provides evidences for the role of neurotrophins in schizophrenia.
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PMID:Chronic amphetamine treatment reduces NGF and BDNF in the rat brain. 1743 16

The neurotrophic factors play an important role in the maintenance of neurone viability and neuronal communication which are considered to be altered in schizophrenia. Subchronic application of ketamine (Ket) was found to be a useful model in schizophrenia research. To further validate this model the mRNA levels of neurotrophic factors NGF, NT-3, and BDNF and their receptors TrkA, TrkB, and TrkC, respectively, were measured in different brain areas in Ket-pretreated rats subchronically dosed with the atypical antipsychotic drug risperidone (Ris). With the exception of NGF in the frontal cortex, Ket pretreatment did change NGF, NT-3, and BDNF mRNA levels in the frontal cortex, the hippocampus, the striatum, the thalamus/hypothalamus region, and in the cerebellum. These changes correspond with changes at their tyrosine kinase receptors. Ris treatment normalised altered NT-3 levels in the hippocampus and balanced BDNF levels in the same structure. It was concluded that the Ket model might reflect distinct alterations in neurotrophic factor activity as found in schizophrenic patients and, moreover, that Ris treatment rebalances disturbed neurotrophic factor activity.
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PMID:Expression of mRNA of neurotrophic factors and their receptors are significantly altered after subchronic ketamine treatment. 1847 18

The relationship between MRI-parameters of frontal lobes and levels of autoantibodies to nerve growth factor (Aab-NGF) in the blood serum of patients with schizophrenia and their relatives was studied. The negative correlation between the Aab-NGF level and the total volume of frontal lobes (r= -0,59; p<0,01) was found in the group of patients. No significant correlations were found in the control groups of healthy subjects without family history of schizophrenia and relatives of patients. The authors concede that Aab-NGF may play a substantial role in the development of neuromorphological changes in schizophrenia.
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PMID:[MRI-parameters of frontal lobes in schizophrenia: correlations with the level of autoantibodies to nerve growth factor in the blood serum]. 1936 91

Altered neuroplasticity contributes to the pathophysiology of schizophrenia. However, the idea that antipsychotics may act, at least in part, by normalizing neurogenesis has not been consistently supported. Our study seeks to determine whether hippocampal cell proliferation is altered in adult rats pretreated with ketamine, a validated model of schizophrenia, and whether chronic administration with neuroleptic drugs (haloperidol and risperidone) affect changes of cell genesis/survival. Ketamine per se has no effect on cell proliferation. Its withdrawal, however, significantly induced cell proliferation/survival in the hippocampus. Risperidone and haloperidol supported cell genesis/survival as well. During ketamine withdrawal, however, their application did not affect cell proliferation/survival additionally. TUNEL staining indicated a cell-protective potency of both neuroleptics with respect to a ketamine-induced cell death. As RT-PCR and Western blot revealed that the treatment effects of risperidone and haloperidol seemed to be mediated through activation of VEGF and MMP2. The mRNA expression of NGF, BDNF, and NT3 was unaffected. From the respective receptors, only TrkA was enhanced when ketamine withdrawal was combined with risperidone or haloperidol. Risperidone also induced BCL-2. Ketamine withdrawal has no effect on the expression of VEGF, MMP2, or BCL-2. It activated the expression of BDNF. This effect was normalized by risperidone or haloperidol. The findings indicate a promoting effect of risperidone and haloperidol on survival of young neurons in the hippocampus by enhancing the expression of the anti-apoptotic protein BCL-2 and by activation of VEGF/MMP2, whereby an interference with ketamine and thus a priority role of the NMDA system was not evident.
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PMID:Risperidone and haloperidol promote survival of stem cells in the rat hippocampus. 1957


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