Increased expression of Wnt-1 in schizophrenic brains

Miyaoka, Tsuyoshi; Seno, Haruo; Ishino, Hiroshi

doi:10.1016/s0920-9964(98)00179-0

Cited by 150 publications

(90 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…17,20 Several researches have reported that abnormalities of neural cell adhesion, neuronal function, and Wnt/Wingless exist in schizophrenia. [10][11][12][13][14][15]18,19,[23][24][25][26] Third, APC is located at 5q21-22, which has been previously reported to be linked with schizophrenia. 27,28 Three SNPs of APC are associated with schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

Cui

Jiang

et al. 2005

Mol Psychiatry

View full text Add to dashboard Cite

The etiology of schizophrenia is unclear, although family, twin, and linkage studies implicate genetic factors. Here, we identified adenomatous polyposis coli (APC), a tumor suppressor gene, as a risk factor for schizophrenia. We compared leukocytic gene expression patterns of six pairs of patients with schizophrenia and healthy controls by microarray. APC expression levels were significantly increased in all patients compared to healthy controls. To confirm the findings of microarray analysis, we measured expression levels of APC in the leukocytes from 30 relapse patients taking antipsychotic medication, 29 first-episode drug-naïve patients, and 30 healthy controls using real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR). APC expression levels were significantly increased in leukocytes of schizophrenics both taking and not taking antipsychotic medication and hence the increase of APC expression was not due to antipsychotic medication. APC is located at 5q21-22, which has been previously reported to be linked with schizophrenia. Further, we performed the transmission disequilibrium test (TDT) and TDT based on haplotypes to search for the association between schizophrenia and APC by examining 163 parent-offspring trios of Chinese descent. We analyzed three single-nucleotide polymorphisms (SNPs) (rs2229992, rs42427, rs465899) at the exon region of APC. TDT showed that the three SNPs are significantly associated with schizophrenia (TDT v 2 ¼ 4.23, Po0.05; 4.15, Po0.05; 8.49 Po0.01, respectively; HHRRv 2 ¼ 5.54, Po0.05; 4.40, Po0.05; 9.79, Po0.01, respectively). We found a significant association between the APC haplotypes from rs2229992-rs42427-rs465899 and schizophrenia (Global v 2 ¼ 44.376,df ¼ 7, Po0.001). The C-A-T haplotype has a frequency of more than 57% and has a strong association with schizophrenia (v 2 ¼ 15.04, Po0.001). These results indicate that the APC may be a candidate gene conferring susceptibility to schizophrenia and also may be associated with reduced vulnerability to cancer in schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 99%

“…9 Recently, evidences for potential disturbances of Wnt signaling pathways in schizophrenia have accumulated. [10][11][12][13][14][15] However, as far as the authors are aware, the involvement of APC in schizophrenia has not been reported. The immunoprecipitation experiment results suggested that APC is involved in cell adhesion.…”

mentioning

confidence: 94%

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

Cui

Jiang

et al. 2005

Mol Psychiatry

View full text Add to dashboard Cite

show abstract

“…Currently, several reports suggest that the localization or levels of Wnt signaling components are altered in the cortex, subiculum and hippocampus -particularly in CA3 and CA4 regions of the pyramidal cell layer -in schizophrenic patients compared to unaffected individuals. Indeed, Wnt-1 immunoreactivity (Miyaoka et al, 1999), as well as intraneuronal staining of b-catenin and g-catenin (Cotter et al, 1998), is altered in post-mortem brains of schizophrenic subjects, suggesting an altered plasticity in a large proportion of schizophrenic brains. More recently, gene expression analysis of the Wnt signaling antagonist Dickkopf-3 (Dkk3) has shown that its transcript is downregulated in cortical neurons of schizophrenic brains (Ftouh et al, 2005).…”

Section: Schizophrenia and Polymorphisms In Frizzled 3 And Gsk3bmentioning

confidence: 99%

The ups and downs of Wnt signaling in prevalent neurological disorders

2006

View full text Add to dashboard Cite

In order to function properly, the brain must be wired correctly during critical periods in early development. Mistakes in this process are hypothesized to occur in disorders like autism and schizophrenia. Later in life, signaling pathways are essential in maintaining proper communication between neuronal and non-neuronal cells, and disrupting this balance may result in disorders like Alzheimer's disease. The Wnt/b-catenin pathway has a well-established role in cancer. Here, we review recent evidence showing the involvement of Wnt/b-catenin signaling in neurodevelopment as well as in neurodegenerative diseases. We suggest that the onset/development of such pathological conditions may involve the additive effect of genetic variation within Wnt signaling components and of molecules that modulate the activity of this signaling cascade.

show abstract

“…Loss of Wnt1 expression [3,4] leads to apoptosis while the presence of Wnt1 can promote cell survival during insults such as serum deprivation [5]. In the nervous system, altered Wnt1 signaling may incite functional cognitive impairment [6], lead to retinal degeneration [7], and in experimental models, affect amyloid precursor protein metabolism [8] and neurofibrillary pathology [9].…”

Section: Introductionmentioning

confidence: 99%

Cellular demise and inflammatory microglial activation during β-amyloid toxicity are governed by Wnt1 and canonical signaling pathways

Chong

Maiese

2007

Cellular Signalling

164

View full text Add to dashboard Cite

Initially described as a modulator of embryogenesis for a number of organ systems, Wnt1 has recently been linked to the development of several neurodegenerative disorders, none being of greater significance than Alzheimer's disease. We therefore examined the ability of Wnt1 to oversee vital pathways responsible for cell survival during β-amyloid (Aβ 1-42 )exposure. Here we show that Wnt1 is critical for protection in the SH-SY5Y neuronal cell line against genomic DNA degradation, membrane phosphatidylserine (PS) exposure, and microglial activation, since these neuroprotective attributes of Wnt1 are lost during gene silencing of Wnt1 protein expression. Intimately tied to Wnt1 protection is the presence and activation of Akt1. Pharmacological inhibition of the PI 3-K pathway or gene silencing of Akt1 expression can abrogate the protective capacity of Wnt1. Closely aligned with Wnt1 and Akt1 are the integrated canonical pathways of synthase kinase-3β (GSK-3β) and β-catenin. Through Akt1 dependent pathways, Wnt1 phosphorylates GSK-3β and maintains β-catenin integrity to insure its translocation from the cytoplasm to the nucleus to block apoptosis. Our work outlines a highly novel role for Wnt1 and its integration with Akt1, GSK-3β, and β-catenin to foster neuronal cell survival and repress inflammatory microglial activation that can identify new avenues of therapy against neurodegenerative disorders.

show abstract

Increased expression of Wnt-1 in schizophrenic brains

Cited by 150 publications

References 21 publications

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

The ups and downs of Wnt signaling in prevalent neurological disorders

Cellular demise and inflammatory microglial activation during β-amyloid toxicity are governed by Wnt1 and canonical signaling pathways

Contact Info

Product

Resources

About