A quantitative study on the expression of synapsin II and N-ethylmaleimide-sensitive fusion protein in schizophrenic patients

Imai, China; Sugai, Tetsuji; Iritani, Shuji; Niizato, Kazuhiro; Nakamura, Ryosuke; Makifuchi, Takao; Kakita, Akiyoshi; Takahashi, Hitoshi; Nawa, Hiroyuki

doi:10.1016/s0304-3940(01)01844-4

Cited by 40 publications

(25 citation statements)

References 17 publications

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“…Not all presynaptic markers, however, appear to decline; protein levels of synapsin II are maintained in this region in schizophrenic patients (Karson et al 1999;Imai et al 2001). Similarly, we observed no significant alteration in other PDZ molecules, most of which are localized at postsynaptic sites.…”

Section: Discussioncontrasting

confidence: 39%

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Toyooka

Iritani

Makifuchi

et al. 2002

Journal of Neurochemistry

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111

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Many postsynaptic density proteins carrying postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain(s) interact with glutamate receptors to control receptor dynamics and synaptic plasticity. Here we examined the expression of PDZ proteins, synapse-associated protein (SAP) 97, postsynaptic density (PSD)-95, chapsyn-110, GRIP1 and SAP102, in post-mortem brains of schizophrenic patients and control subjects, and evaluated their contribution to schizophrenic pathology. Among these PDZ proteins, SAP97 exhibited the most marked change: SAP97 protein levels were decreased to less than half that of the control levels specifically in the prefrontal cortex of schizophrenic patients. In parallel, its binding partner, GluR1, similarly decreased in the same brain region. The correlation between SAP97 and GluR1 levels in control subjects was, however, altered in schizophrenic patients. SAP102 levels were also significantly reduced in the hippocampus of schizophrenic patients, but this reduction was correlated with sample storage time and post-mortem interval. There were no changes in the levels of the other PDZ proteins in any of the regions examined. In addition, neuroleptic treatment failed to mimic the SAP97 change. These findings suggest that a phenotypic loss of SAP97 is associated with the postsynaptic impairment in prefrontal excitatory circuits of schizophrenic patients. Keywords: chapsyn-110, GRIP1, PSD-95, psychosis, SAP102, SAP97. Address correspondence and reprint requests to Hiroyuki Nawa, Department of Molecular Biology, Brain Research Institute, Niigata University, Asahimachi-dori 1-757, Niigata 951-8585, Japan. E-mail: hnawa@bri.niigata-u.ac.jpAbbreviations used: ABP, AMPA receptor-binding protein; AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid; BDNF, brainderived neurotrophic factor; DTT, dithiothreitol; LPT, long-term potentiation; NSE, neuron-specific enolase; PAGE, polyacrylamide gel electrophoresis; PDZ, PSD-95/discs large/zone occludens-1; PVDF, polyvinylidene difluoride; PSD, postsynaptic density; SAP, synapseassociated protein; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

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Section: Discussioncontrasting

confidence: 39%

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Toyooka

Iritani

Makifuchi

et al. 2002

Journal of Neurochemistry

Self Cite

111

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“…A microarray expression profile of the prefrontal cortex revealed that Syn2 transcript levels were significantly decreased in nine out of ten subjects with schizophrenia as compared to ten matched controls (Mirnics et al 2000). Although this finding was not confirmed by real-time PCR and immunoblotting experiments in another sample (Imai et al 2001), another Western immunoblotting study found a decrease in synapsin (IIa and IIIa) expression in the hippocampus of individuals with schizophrenia (Vawter et al 2002). Syn2 transcript levels were significantly up-regulated in immunoblotting experiments in rats following chronic haloperidol treatment (Chong et al 2002), implying a possible role in reaction to perturbations of the dopamine system.…”

Section: Introductionmentioning

confidence: 85%

Association of synapsin 2 with schizophrenia in families of Northern European ancestry

Saviouk

Moreau

Tereshchenko

et al. 2007

Schizophrenia Research

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The synapsin 2 (Syn2) gene (3p25) is implicated in synaptogenesis, neurotransmitter release, and the localization of nitric oxide synthase to the proximity of its targets. In this study we investigated linkage and association between the Syn2 locus and schizophrenia. 37 pedigrees of Northern European ancestry from the NIMH Human Genetics Initiative collection were used. Four microsatellites and twenty SNPs were genotyped. Linkage (FASTLINK) and association (TRANSMIT, PDTPHASE) between markers and schizophrenia were evaluated. A maximum heterogeneity LOD of 1.93 was observed at marker D3S3434 with a recessive mode of inheritance. Significant results were obtained for association with schizophrenia using TRANSMIT (minimum nominal p=0.0000005) and PDTPHASE (minimum nominal p=0.014) using single marker analyses. Haplotype analysis using markers in introns 5 and 6 of Syn2 provided a single haplotype that is significantly associated with schizophrenia using TRANSMIT (nominal p<0.00000001) and PDTPHASE (nominal p=0.02). Simulation studies confirm the global significance of these results, but demonstrate that the small p-values generated by the bootstrap routine of TRANSMIT can be consistently anticonservative. Review of the literature suggests that Syn2 is likely to be involved in the etiology or pathogenesis of schizophrenia.

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“…56 However, in a subsequent study, the decrease in the NSF gene was not significant. 57 A Western Blot analysis also failed to reproduce findings of an alteration in the NSF levels in the PFC (BA9, 10 and 46). 58 The discrepancy between these studies may be due to the location of NSF within subsets of cells differentially affected in schizophrenia and/or to specific anatomical locations in schizophrenia.…”

Section: Synaptic Proteinsmentioning

confidence: 95%

A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia

et al. 2006

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The Anterior Cingulate Cortex (ACC, Brodmans Area 24) is implicated in the pathogenesis of schizophrenia due to its normal functions and connectivity together with reports of structural, morphological and neurotransmitter aberrations within this brain area in the disease state. Two-dimensional gel electrophoresis (2DE) was employed to scan and compare the ACC gray matter proteomes between schizophrenia (n = 10) and control (n = 10) post-mortem human tissue. This proteomic approach has detected 42 protein spots with altered levels in the schizophrenia cohort, which to our knowledge is the first proteomic analysis of the ACC in schizophrenia. Thirty nine of these proteins were subsequently identified using mass spectrometry and functionally classified into metabolism and oxidative stress, cytoskeletal, synaptic, signalling, trafficking and glial-specific groups. Some of the identified proteins have previously been implicated in the disease pathogenesis and some offer new insights into schizophrenia. Investigating these proteins, the genes encoding these proteins, their functions and interactions may shed light on the molecular mechanisms underlying the heterogeneous symptoms characteristic of schizophrenia.

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A quantitative study on the expression of synapsin II and N-ethylmaleimide-sensitive fusion protein in schizophrenic patients

Cited by 40 publications

References 17 publications

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Association of synapsin 2 with schizophrenia in families of Northern European ancestry

A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia

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