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)

Synapsin II (formerly known as protein III) is a synaptic vesicle-associated neuronal phosphoprotein that may be involved in the regulation of neurotransmitter release. Synapsin II was studied in postmortem brain samples from 132 individuals with various neuropsychiatric and medical diagnoses. Molecular weight variants of synapsin II were present in 73% of samples from alcoholic individuals but in only 31% of samples from non-diseased individuals, thus confirming our two previous reports of an association between synapsin II variants and alcoholism. The presence of synapsin II variants was not correlated with age or nutritional state. Synapsin II variants were also present in 56% of samples from individuals with schizophrenia and 41% of samples from individuals with Huntington's disease. Synapsin II variants were present in samples from children and young adults, consistent with the possibility that synapsin II variants may reflect a genetically inherited trait. Synapsin II variants were not found in any of 18 rodent models of alcoholism, aging, or vitamin B deficiency, suggesting that synapsin II variants may be a uniquely human trait.
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PMID:An analysis of synapsin II, a neuronal phosphoprotein, in postmortem brain tissue from alcoholic and neuropsychiatrically ill adults and medically ill children and young adults. 214 98

Microarray expression profiling of prefrontal cortex from matched pairs of schizophrenic and control subjects and hierarchical data analysis revealed that transcripts encoding proteins involved in the regulation of presynaptic function (PSYN) were decreased in all subjects with schizophrenia. Genes of the PSYN group showed a different combination of decreased expression across subjects. Over 250 other gene groups did not show altered expression. Selected PSYN microarray observations were verified by in situ hybridization. Two of the most consistently changed transcripts in the PSYN functional gene group, N-ethylmaleimide sensitive factor and synapsin II, were decreased in ten of ten and nine of ten subjects with schizophrenia, respectively. The combined data suggest that subjects with schizophrenia share a common abnormality in presynaptic function. We set forth a predictive, testable model.
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PMID:Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. 1108 83

The application of DNA array technology to schizophrenic studies enabled us to assess molecular features of this disease. The expression of synapsin II and N-ethylmaleimide-sensitive fusion protein (NSF) mRNAs is reported to decrease in the prefrontal cortex of these patients. We attempted to reproduce this result with two distinct approaches. With high quality samples, mRNA and protein levels for synapsin II and NSF were measured by real-time polymerase chain reaction and by immunoblotting. Both experiments led to the same conclusion: The expression of these presynaptic markers is not altered significantly in the prefrontal cortex of our schizophrenic samples, compared to that in control subjects. These observations suggest that the neurochemical impairments of synapses reported in schizophrenia are not evident for all presynaptic markers and needs to be re-evaluated at molecular levels.
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PMID:A quantitative study on the expression of synapsin II and N-ethylmaleimide-sensitive fusion protein in schizophrenic patients. 1140 36

The cDNA expression array is a recently developed scientific tool that can profile the differential expression of several hundreds of genes simultaneously and is therefore advantageous in the study of antipsychotic drug action at the genetic level. Using this technology, we discovered 14 genes in the rat striatum whose expression was changed by >/= 50% following chronic haloperidol treatment. Among them was the synapsin II gene, which was found to be significantly up-regulated after the treatment. Since recent studies have implicated this gene in schizophrenia, further experiments were performed to determine whether chronic haloperidol exposure resulted in concurrent increases in the expression of striatal synapsin II protein. Immunoblotting revealed that protein levels of both the a and b isoforms of synapsin II were also increased by comparable amounts following haloperidol treatment. This study is the first to show the regulation of synapsin II expression by haloperidol at the transcript and protein level in rat striatum. A possible mechanism for the observed haloperidol-induced increase in striatal synapsin II expression, along with the implications of this up-regulation in chronic haloperidol treatment, is presented.
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PMID:cDNA array reveals differential gene expression following chronic neuroleptic administration: implications of synapsin II in haloperidol treatment. 1235 1

Synapsin II has been proposed as a candidate gene for vulnerability to schizophrenia on the basis of its function and its location in a region of the genome implicated by linkage studies in families with schizophrenia. We recently reported positive association of synapsin II with schizophrenia in a case-control study (Chen et al. 2004). However, since case-control analyses can generate false-positive results in the presence of minor degrees of population stratification, we have performed a replication study in 366 additional Han Chinese probands and their parents by use of analyses of transmission/disequilibrium for three in/del markers and three single-nucleotide polymorphisms. Positive association was observed for rs2307981 (P =.02), rs2308169 (P =.005), rs308963 (P =.002), rs795009 (P =.02), and rs2307973 (P =.02). For transmission of six-marker haplotypes, the global P value was.0000016 (5 degrees of freedom), principally because of overtransmission of the most common haplotype, CAA/-/G/T/C/- (frequency 53.6%; chi (2) = 20.8; P =.0000051). This confirms our previous study and provides further support for the role of synapsin II variants in susceptibility to schizophrenia.
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PMID:Family-based association study of synapsin II and schizophrenia. 1544 41

We previously demonstrated that chronic treatment with the dopamine-D2 receptor antagonist, haloperidol, increases mRNA and protein content of the phosphoprotein, synapsin II, in the rat striatum. Since dopamine-D2 receptor antagonism and dopamine-D1 receptor blockade can have opposing effects on gene expression, the present investigation compared the effects of haloperidol with those of the dopamine-D1 receptor antagonist, R-[+]-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390), on the expression of synapsin II protein. Haloperidol and SCH23390 respectively elevated and reduced concentrations of the molecule in mouse primary midbrain cell cultures. Additional experiments revealed that the dopamine-D1 receptor agonist, R-[+]-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzapezine-7,8-diol (SKF38393), upregulated the phosphoprotein in these cells. Furthermore, in vivo rat studies demonstrated that chronic haloperidol treatment increases synapsin II protein expression in the medial prefrontal cortex and nucleus accumbens, as was observed in the striatum. In contrast, chronic SCH23390 administration reduced concentrations of this protein in all of these regions, although the reductions seen in the medial prefrontal cortex were insignificant. Neither haloperidol nor the dopamine-D1 receptor antagonist affected synapsin I protein expression in any of the studied brain areas. Based on these findings, we propose dopamine receptors may specifically regulate synapsin II expression through a cyclic AMP-dependent pathway. Since synapsin II is involved in neurotransmitter release and synaptogenesis, and changes in synaptic efficacy and structure are suggested in schizophrenia as well as in haloperidol treatment, our findings offer insight into the mechanistic actions of the antipsychotic agent at the synaptic level.
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PMID:Dopamine-D1 and -D2 receptors differentially regulate synapsin II expression in the rat brain. 1641 26

Repeated administration of methamphetamine (MAP) results in an increased behavioral response to the drug during subsequent exposure. This phenomenon is called behavioral sensitization. Sensitization is an enduring phenomenon, and suggests chronic alterations in neuronal plasticity. MAP-induced sensitization has been proposed and widely investigated as an animal model of MAP psychosis and schizophrenia. However, little is known about the molecular mechanisms underlying MAP-induced sensitization. 2-DE-based proteomics allows us to examine global changes in protein expression in complex biological systems and to propose hypotheses concerning the mechanisms underlying various pathological conditions. In the present study, we examined protein expression profiles in the striatum of MAP-sensitized rats using 2-DE-based proteomics. Repeated administration of MAP (4.0 mg/kg, once a day, intraperitoneal (i.p.)) for 10 days significantly augmented the locomotor response to an MAP challenge injection (1.0 mg/kg, i.p.) on day 11. This enhanced activity was maintained even after a week of drug abstinence. 2-DE analysis revealed 42 protein spots were differentially regulated in the striatum of MAP-sensitized rats compared to control. Thirty-one protein spots were identified using MALDI-TOF, including synapsin II, synaptosomal-associated protein 25 (SNAP-25), adenylyl cyclase-associated protein 1 (CAP1), and dihydropyrimidinase-related protein 2 (DRP2). These proteins can be related to underlying mechanisms of MAP-induced behavioral sensitization, indicating cytoskeletal modification, and altered synaptic function.
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PMID:Protein expression profile in the striatum of rats with methamphetamine-induced behavioral sensitization. 1735 86

Recent studies on the phosphoprotein synapsin II have revealed reduced expression in postmortem medial prefrontal cortex tissues from subjects with schizophrenia, and chronic antipsychotic drug treatment has resulted in concurrent increases in synapsin II mRNA and protein levels. Collectively, this research suggests a role of synapsin II in the pathophysiology of schizophrenia; however, whether synapsin II plays a causal role in this disease process still remains unclear. Therefore, the goal of this investigation was to examine whether synapsin II knockout mice display behavioral abnormalities commonly expressed in preclinical animal models of schizophrenia, namely deficits in prepulse inhibition (PPI), decreased social behavior, and locomotor hyperactivity. Results indicate that mice with knockout of the synapsin II gene demonstrate deficits in PPI at three prepulse intensities (67, 70, and 73 dB), along with deficits in habituation to startle to a 110 dB acoustic pulse. Knockout animals also expressed decreased social behavior and increased locomotor activity when compared to wildtype and heterozygous populations. Complete knockout of the synapsin II gene was confirmed in postmortem brain tissues via immunoblotting. In conclusion, these results confirm that synapsin II knockout mice display behavioral endophenotypes similar to established preclinical animal models of schizophrenia, and lend support to the notion that abnormalities in synapsin II expression may play a causal role in the underlying pathophysiological mechanisms of schizophrenia.
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PMID:Behavioral abnormalities in synapsin II knockout mice implicate a causal factor in schizophrenia. 1936 Aug 55

Membrane microdomains (MM) are membrane rafts within the cell membrane enriched in cholesterol and glycosphingolipids that have been implicated in the trafficking and sorting of membrane proteins, secretory and endocytotic pathways, and signal transduction. To date, MM have not been characterised in the human brain. We reason that by identifying MM in the normal human cortex, we may better understand the molecular mechanisms of human brain dysfunction. To characterize the protein composition of MM in the human brain, we have carried out a comprehensive proteomic analysis of detergent resistant membranes (DRMs) associated proteins derived from human postmortem insular cortex using 1-DE separation prior to LC coupled to MS/MS or GeLC-MS/MS. Eighty five proteins were identified including 57 unique to human brain cortex DRMs (by comparison with DRM proteins reported in other cell types). High levels of signal transduction, cell adhesion, cell transport and cell trafficking proteins were identified including synaptic proteins such as synapsin II and synaptic vesicle membrane protein, mitochondrial proteins such as ATPase subunits and metabolic enzymes such as malate dehydrogenase. This data will facilitate our understanding of protein expression changes within membranes in candidate brain regions in human brain diseases such as schizophrenia, bipolar disorder and other psychiatric and neurodegenerative disorders.
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PMID:Analysis of membrane microdomain-associated proteins in the insular cortex of post-mortem human brain. 2113 29

Synapsin II is a synaptic vesicle-associated phosphoprotein that has been implicated in the pathophysiology of schizophrenia. Studies have demonstrated reductions in synapsin II mRNA and protein in medial prefrontal cortical post-mortem samples from patients with schizophrenia, genetic associations between synapsin II and schizophrenia, and synapsin II protein regulation by dopamine receptor activation. Collectively, this research indicates a relationship between synapsin II dysregulation and schizophrenia; however, it remains unknown whether perturbations in synapsin II play a role in the pathophysiology of this disease. The aim of this project was to evaluate animals with selective knock-down of synapsin II in the medial prefrontal cortex. After continuous infusion of synapsin II antisense sequences, animals were examined for the presence of schizophrenic-like behavioral phenotypes and assessed on the response to clinically relevant antipsychotic drugs. Our results indicate that rats with selective reductions in medial prefrontal cortical synapsin II demonstrate deficits in sensorimotor gating (prepulse inhibition), reduced social behavior, and hyperlocomotion, which are corrected by the atypical antipsychotic drug olanzapine. Additionally, synapsin II knock-down disrupts serial search efficiency. These behavioral changes are accompanied by reductions in vesicular neurotransmitter transporter protein concentrations for glutamate (VGLUT1 and VGLUT2) and GABA (VGAT), without affecting dopamine (VMAT2). These results implicate a causal role for decreased synapsin II in the medial prefrontal cortex in the pathophysiology of schizophrenia and the mechanisms of aberrant prefrontal cortical circuitry, and suggest that synapsin II may potentially serve as a novel therapeutic target for this disorder.
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PMID:Medial prefrontal cortical synapsin II knock-down induces behavioral abnormalities in the rat: examining synapsin II in the pathophysiology of schizophrenia. 2168 7


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