Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia

Vawter, Marquis P.; Howard, Allyson; Hyde, T M; Kleinman, Joel E.; Freed, William J.

doi:10.1038/sj.mp.4000547

Cited by 97 publications

(50 citation statements)

References 48 publications

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“…21 In bipolar patients, the synaptophysin/actin ratio was also smaller by approximately 40%, but this difference was not statistically significant. In the present study, no change in synaptophysin was found.…”

Section: Discussionmentioning

confidence: 98%

“…21 However, the use of housekeeping genes as standards of reference for normalization, and the use of actin in particular, has recently been questioned. 36,37 Therefore, synaptophysin was employed in the present study as a reference standard and as an alternative measure of synaptic protein expression, but was not used to normalize the synapsin measurements.…”

Section: Western Blotsmentioning

confidence: 99%

“…[16][17][18]20 In a prior study, we found modest decreases in synaptophysin protein as normalized to actin in patients with schizophrenia, but no change in bipolar disorder. 21 A recent microarray study of prefrontal cortex identified genes for presynaptic proteins in general, and particularly N-ethylmaleimide sensitive factor and synapsin, as showing consistent decreases in schizophrenia. 22 Thus, although synaptophysin has been studied in schizophrenia in considerably greater detail than synapsin, there are some indications that decreases in expression of synapsin may be considerably more pronounced.…”

Section: Introductionmentioning

confidence: 99%

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Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia

et al. 2002

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Several studies suggest that decreased expression of presynaptic proteins may be characteristic of schizophrenia. We examined one such protein, synapsin, in schizophrenia and bipolar disorder. Samples of hippocampal tissue from controls (n = 13), patients with schizophrenia (n = 16), or bipolar disorder (n = 6), and suicide victims (n = 7) were used. The membrane and cytosolic fractions were analyzed by Western immunoblotting for synapsin using an antibody that detects synapsin Ia, IIa, and IIIa proteins. Synaptophysin was also measured for comparison. Total synapsin was decreased significantly in patients with schizophrenia (P = 0.034) and in bipolar disorder (P = 0.00008) as compared to controls. The synapsin/synaptophysin ratios were decreased in schizophrenia and bipolar disorder, and additionally in suicide victims (P = 0.014). Age, postmortem interval, percentage of protein extracted, and pH of brain were not different between groups. No changes in total synapsin or synaptophysin in the hippocampus were produced by injecting rats with either lithium or haloperidol for 30 days. Reductions in synapsin in both patients with schizophrenia (synapsin IIa and IIIa) and bipolar disorder (synapsin Ia, IIa and IIIa) imply that altered or reduced synaptic function in the hippocampus may be involved in these disorders.

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Section: Discussionmentioning

confidence: 98%

Section: Western Blotsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia

et al. 2002

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“…[4][5][6][7][8] Recently we reported that expression of two other such proteins, complexin (cx) I and its homologue cx II, is also reduced, supporting the existence of synaptic pathology in the disorder. 9 In addition, we found that at both mRNA and protein level, the ratio of the two gene products was altered, with cx II decreased more than cx I.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs

2000

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Complexin (cx) I and cx II are synaptic proteins preferentially expressed by inhibitory and excitatory hippocampal neurons respectively. We previously reported decreased hippocampal formation cx mRNA and protein expression in schizophrenia, with a greater loss of cx II than cx I. The present in situ hybridization study was both an attempt at replication, and an extension to include bipolar and unipolar mood disorders, using sections from the Stanley Foundation brain series. In schizophrenia, both mRNAs were decreased in some hippocampal subfields, especially CA4, but were preserved in subiculum. The cx II/cx I mRNA ratio was unchanged. In bipolar disorder, the mRNAs were reduced in CA4, subiculum and parahippocampal gyrus, with the deficit in subiculum being diagnostically specific. No alterations in cx mRNAs were found in major depression. Treatment of rats with antipsychotics (haloperidol or chlorpromazine) for 2 weeks had no effect on hippocampal cx mRNAs. These data replicate the finding of decreased cx I and cx II expression in the hippocampus in schizophrenia and show a similar or greater abnormality in bipolar disorder. Non-replication of the cx II Ͼ cx I mRNA loss in schizophrenia means that the hypothesis of a preferential involvement of excitatory connections was not supported. The results extend the emerging evidence that altered circuitry may be a component of the neuroanatomy of both schizophrenia and bipolar mood disorder. Molecular Psychiatry (2000) 5, 425-432.

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“…Finally, a decrease in SNAP-25 and synaptophysin proteins has been found in the brains of schizophrenics. [12][13][14][15][16] Interestingly, a number of genes encoding SNARE and vesicle proteins map to regions of the genome that are suspected to harbor BPD and SZ susceptibility genes. SNAP29, RAB36, synapsin III and synaptogyrin 1 map to chromosome 22q11-13, synapsin I and synaptophysin map to Xp11, SYBL1 maps to Xq28, and syntaxin 7 maps to chromosome 6q21.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in SNAP29 gene promoter region associated with schizophrenia

et al. 2001

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Linkage studies indicate that chromosome 22q contains a locus, or loci, for schizophrenia (SZ) and bipolar disorder (BPD). Furthermore, the congenital disorder velo cardio facial syndrome (VCFS), which is usually caused by a 22q11 microdeletion, is associated with an increased prevalence of psychiatric disease, including SZ and BPD. One plausible candidate gene that maps to 22q11, in a region deleted in the most common form of VCFS, is SNAP29, a member of the SNAP-25 family of SNARE proteins. To search for possible functional mutations in SNAP29 that could be analyzed as candidates for 22q11-linked psychiatric problems, exons, intron-exon junctions and the promoter region were screened. No coding variants were found, although a silent mutation at codon 6 and three single nucleotide polymorphisms (SNPs) were identified in the 5Ј untranslated and promoter regions. One SNP, an A→G transition 849 nucleotides upstream of the transcription start site, showed a moderately significant difference in the distribution of alleles and genotypes in patients with SZ compared with controls (allele frequency: 2 = 5.57, 1 df, P = 0.018; genotype: 2 = 9.49, 2 df, P = 0.009; odds ratio = 1.59, 95% Cl = 1.08-2.34). No significant difference was found in patients with BPD. Although the functional significance of this mutation is not known, the tetranucleotide core sequence of the ets and IK2 families of transcription factors is altered as a result of the SNP. These data suggest that a mutation in the SNAP29 gene promoter region, or a mutation in linkage disequilibrium with the promoter SNP, may be involved in the pathogenesis of chromosome 22-linked SZ. Molecular Psychiatry (2001) 6, 193-201.

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Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia

Cited by 97 publications

References 48 publications

Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia

Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia

Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs

Polymorphism in SNAP29 gene promoter region associated with schizophrenia

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