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)

Post-mortem brain tissue was obtained from four patients with schizophrenia and five controls to study cell groups in the brain stem reticular formation. Cholinergic neurons in the pedunculopontine nucleus (PPN) and lateral dorsal tegmental nucleus (LDT) were labeled using nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry, while catecholaminergic neurons of the locus ceruleus (LC) were labeled immunocytochemically using an antibody to tyrosine hydroxylase. In schizophrenic patients, there were increased numbers of neurons in the PPN labeled by NADPH-diaphorase and reduced cell size in the LC. These results implicate the reticular formation as a possible pathophysiological site for at least some patients with schizophrenia. This also suggests that some of the deficits observed may be based on faulty neurodevelopment.
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PMID:The brain stem reticular formation in schizophrenia. 168 69

Findings reported here show that there is a significant increase in the number of neurons in the pedunculopontine nucleus in most schizophrenic patients compared to age-matched controls. Nicotinamide adenine dinucleotide phosphate diaphorase histochemistry was used to label putative cholinergic neurons in the pedunculopontine nucleus and laterodorsal tegmental nucleus, while noradrenergic locus coeruleus neurons were labeled immunocytochemically using an antibody to tryosine hydroxylase. Cell counts of these neuronal groups were carried out using a Biographics image analysis system. We found significantly increased cell numbers in the pedunculopontine nucleus of schizophrenic patients compared to controls. The number of laterodorsal tegmental nucleus neurons was increased but this was not statistically significant. However, the total cell counts for pedunculopontine and laterodorsal tegmental nuclei were significantly higher in schizophrenic subjects. The number of locus coeruleus noradrenergic neurons was similar in both groups. These results implicate the brainstem reticular formation as a pathophysiological site in at least some patients with schizophrenia. In addition, these findings suggest a developmental etiology for the disease and account for some, but not all, of the symptoms of schizophrenia, including sensory gating abnormalities, sleep-wake disturbances and, perhaps, hallucinations. Overdriving of thalamic and substantia nigra function by cholinergic afferents from the midbrain may account for some of the symptoms seen in schizophrenia. These findings suggest that, at least in some schizophrenic patients, there is an increased number of neurons in the cholinergic arm of the reticular activating system. This may explain some of the symptoms of schizophrenia and points to a prenatal disturbance as one of the possible causes of the disease.
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PMID:Mesopontine neurons in schizophrenia. 747 75

Epidemiological and anatomical studies support the theory that disturbances of brain development may play a contributory role in the etiology of schizophrenia. Anatomical findings suggest that the normal pattern of neuronal migration during development of the cerebral cortex may be affected in the brains of schizophrenics, with the implication that cortical connectivity and associative function will be disrupted. In the present investigation in matched schizophrenic and control brains, we examined a particular population of neurons found in the prefrontal cortex and underlying white matter and characterized by histochemical staining for the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase. In normal brains, these neurons are found in highest numbers in the white matter immediately deep to layer VI of the cortex where they remain from the subplate, an early formed, but transitory structure that plays a key role in cortical development and connection formation. The dorsolateral prefrontal area of schizophrenics showed a significant decline in nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in the superficial white matter and in the overlying cortex but a significant increase in these neurons in white matter deeper than 3 mm from the cortex. These findings are consistent with a disturbance of the subplate during development in which the normal pattern of programmed cell death is compromised and accompanied by a defect in the normal orderly migration of neurons toward the cortical plate. These are likely to have serious consequences for the establishment of a normal pattern of cortical connections leading to a potential breakdown of frontal lobe function in schizophrenics.
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PMID:Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. 767 91

A high proportion of neurons in the cerebellum and in cholinergic brainstem nuclei stain positive for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd), which is a nitric oxide synthase (NOS). Recent evidence suggests that schizophrenia may involve increased numbers of NADPHd-stained neurons in different areas of the subcortex. This led us to examine the actual concentration of NOS in postmortem brain specimens of cerebellum, and the relevant regions of brainstem tegmentum, to see if NOS concentrations were also increased in schizophrenia. Postmortem brain tissue was obtained at autopsy from schizophrenics and controls who did not have other brain disease. In patients with schizophrenia, NOS concentration was higher.
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PMID:Nitric oxide synthase (NOS) in schizophrenia: increases in cerebellar vermis. 914 13

The complete absence of handling of male rats during neonatal development (from birth to postnatal day 21) correlates with an impairment of latent inhibition [J. Feldon, I. Weiner, From an animal model of an attentional deficit towards new insights into the pathophysiology of schizophrenia, J. Psychiatr. Res. 26 (1992) 345-366.]. Such nonhandling of rats reportedly also correlates with a decreased expression of reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) reactivity in the hippocampus in adult rats (6 months of age) when compared with rats of the same age that were handled during the same neonatal period [R.R. Vaid, B.K. Yee, U. Shalev, J.N. Rawlins, I. Weiner, J. Feldon, S. Totterdell, Neonatal nonhandling and in utero prenatal stress reduce the density of NADPH-diaphorase-reactive neurons in the fascia dentata and Ammon's horn of rats, J. Neurosci. 17 (1997) 5599-5609.]. The present study investigated whether such a decrease in NADPHd activity would be detectable at earlier ages. Therefore, the present study assessed the density of nitric oxide (NO) producing neurons in the fascia dentata and Ammon's horn in 28-, 54-, and 118-day-old nonhandled and handled male rats using NADPHd histochemistry and immunohistochemical localization of neuronal isoform of nitric oxide synthase (nNOS), a NADPHd. This showed that in these three age groups, the numbers of NADPHd positive neurons per unit area throughout the hippocampus of rats that received no handling during neonatal development did not differ significantly from those of rats that received regular daily handling. In addition, we found in the rats of 118 days of age that the areal density of nNOS immunopositive neurons in the hippocampus also did not differ significantly between nonhandled and handled rats. Nevertheless, in a parallel study, rats from the same experimental group receiving identical treatments showed the expected impairment of latent inhibition at 4 months of age [R. Weizman, J. Lehmann, S. Leschiner, I. Allmann, T. Stoehr, C. Heidbreder, A. Domeney, J. Feldon, M. Gavish, Long-lasting effect of early handling on the peripheral-type benzodiazepine receptor, Pharmacol. Biochem. Behav. in press.]. These results suggest that nonhandling of rats during the early neonatal period, that does result in impairment in latent inhibition, does not affect the numbers of NO producing neurons in the hippocampus in rats of young ages, including the age of observed impairment of latent inhibition.
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PMID:Comparisons of the densities of NADPHd reactive and nNOS immunopositive neurons in the hippocampus of three age groups of young nonhandled and handled rats. 1032 Jul 62

NADPH-d (nicotinamide-adenine dinucleotide phosphate-diaphorase) neurons are thought to migrate improperly during development in the brains of schizophrenic patients. This enzyme is a nitric oxide synthase (NOS). Nitric oxide (NO) is known to affect neurodevelopmental processes in the CNS. Therefore, we hypothesized that interference of NO generation during development may produce some aspects of schizophrenia symptomatology in a rat model. In these experiments, neonatal rats were challenged with a NOS inhibitor (L-nitroarginine 1-100 mg/kg s.c.) daily on post-natal days 3-5. L-Nitroarginine (L-NoArg) treated male rats developed a hypersensitivity to amphetamine in adulthood versus vehicle treated controls, whereas female rats did not. However, L-NoArg treated female rats developed a hypersensitivity to phencyclidine (PCP) at juvenile and adult ages versus vehicle treated controls, whereas male animals did not. L-NoArg treated male rats also had deficits in pre-pulse inhibition of startle whereas adult female rats did not. The results are discussed in terms of a new neurodevelopmental model of schizophrenia and male/female differences inherent in this disease.
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PMID:On the effect of neonatal nitric oxide synthase inhibition in rats: a potential neurodevelopmental model of schizophrenia. 1047 Oct 83

NAD(P)H: quinone oxidoreductase (NQO1), an obligate two-electron reductase of quinones, prevents their participation in redox cycling and subsequent generation of reactive oxygen species (ROS). Reduced or negative activity of NQO1 would lead to an excess of neurotoxic compounds of cathecolamine o-quinones and ROS. Recently, there has been increasing evidence that catecholamine o-quinones and ROS might contribute to the development of schizophrenia. We investigated the genetic association between a functional polymorphism (Pro 187Ser) in the human NQO1 gene and schizophrenia (244 Japanese schizophrenic patients and 204 healthy controls). No significant differences in the allelic and genotypic distribution between patients and controls were observed. In addition, our results revealed no association between the genotypes of the polymorphism and any characteristics of patients such as gender, age at onset, family history or current neuroleptic dosage. Our results suggest that the NQO1 gene polymorphism does not confer increased susceptibility for schizophrenia in the present sample.
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PMID:NAD(P)H: quinone oxidoreductase (NQO1) gene polymorphism and schizophrenia. 1283 17

The association between the quinone oxidoreductase gene (NQO1) polymorphism (609C/T) and schizophrenia was examined to replicate and extend the findings of a previous study (Hori et al., 2003). The study sample was 107 schizophrenia in-patients and 106 healthy controls. The distributions of the NQO1 genotypes and alleles were not different between the schizophrenia patients and the controls. However, the frequency of the variant genotype was significantly higher in the subgroup with tardive dyskinesia (TD) than in the subgroup without (p=0.019). The subjects with allele T were significantly more frequent in the TD patients than in those without (odds ratio 2.256, 95% confidence interval 1.235-4.133). In addition, the Abnormal Involuntary Movement Scale (AIMS) score was significantly higher in the variant genotype group (T/T) than in other genotypic groups (C/C and C/T) (p=0.004). This study suggests that the NQO1 gene polymorphism (609C/T) may confer susceptibility to the development of TD in schizophrenia, at least in the Korean population.
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PMID:Quinone oxidoreductase (NQO1) gene polymorphism (609C/T) may be associated with tardive dyskinesia, but not with the development of schizophrenia. 1583 2

Treatment with the phencyclidine derivative ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist and a well known anesthetic, has recently been introduced to mimic schizophrenia in animals. Using rats repeatedly treated with sub-anesthetic doses we demonstrate in the hippocampal formation the cellular distribution patterns of proteins being relevant to the pathogenesis of schizophrenia. Compared with controls an increase in the density of reduced nicotinamide adenine dinucleotide phosphate diaphorase-, neuronal nitric oxide synthase- and cFOS-positive hippocampal interneurons was found, whereas the density of parvalbumin expressing cells was decreased. Our experiments show that repeated injections of sub-anesthetic doses of ketamine induce significant changes in the nitrergic and GABAergic system which, in part, resemble those described in postmortem brains of human schizophrenics indicating that sub-chronic treatment with sub-anesthetic doses of ketamine might be a useful animal model to study schizophrenia.
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PMID:Repeated application of ketamine to rats induces changes in the hippocampal expression of parvalbumin, neuronal nitric oxide synthase and cFOS similar to those found in human schizophrenia. 1518 9

Schizophrenia has been suggested to be a neurodevelopmental disorder, and nitric-oxide-synthase (NOS)-positive neurons were shown to be involved in distorted cortical development in schizophrenia. Here we investigated whether nitrinergic neurons in the striatum of schizophrenic patients also display abnormalities regarding distribution or morphology. To do so, postmortem putaminal sections of schizophrenic subjects were examined by means of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) staining and NOS immunohistochemistry. NOS-positive neurons were counted and analyzed morphologically. Abnormalities regarding morphology or number of NOS-containing neurons could be found in the putamen of schizophrenics (n = 3), but not controls (n = 5). Neurons were either of abnormal size and branching pattern, or they were markedly reduced (130 +/- 44 vs. 54 +/- 62 NADPHd-positive somata/mm(3) putamen; p < 0.0001). Striatal nitrinergic interneurons might thus be involved in the pathogenesis of at least some forms of schizophrenia. Studies on larger samples are however needed to further corroborate this finding.
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PMID:Morphological abnormalities in nitric-oxide-synthase-positive striatal interneurons of schizophrenic patients. 1611 Feb 44


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