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Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology
We report an association of single-nucleotide polymorphisms (SNPs) for the VSNL1 gene (visinin-like 1) with schizophrenia and frontal cortical function in a sample of patients with Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) diagnoses of schizophrenia, compared with healthy cont...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309514/ https://www.ncbi.nlm.nih.gov/pubmed/22832524 http://dx.doi.org/10.1038/tp.2011.20 |
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author | Braunewell, K H Dwary, A D Richter, F Trappe, K Zhao, C Giegling, I Schönrath, K Rujescu, D |
author_facet | Braunewell, K H Dwary, A D Richter, F Trappe, K Zhao, C Giegling, I Schönrath, K Rujescu, D |
author_sort | Braunewell, K H |
collection | PubMed |
description | We report an association of single-nucleotide polymorphisms (SNPs) for the VSNL1 gene (visinin-like 1) with schizophrenia and frontal cortical function in a sample of patients with Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) diagnoses of schizophrenia, compared with healthy controls. Moreover, VSNL1 SNPs were associated with performance in the Wisconsin Card Sorting Test, a measure for the assessment of frontal cortical function. The VSNL1 gene product, Visinin-like-protein-1 (VILIP-1), is a member of the neuronal EF-hand Ca(2+)-sensor protein family. Previously, VILIP-1 mRNA and protein expression were shown to be altered in animal models and in schizophrenia patients. VILIP-1 influences cytosolic cyclic adenosine mono phosphate (cAMP) levels, cell migration, exocytotic processes and differentiation in the periphery. This raises the question, whether, similar to other potential schizophrenia susceptibility genes such as Disc1, PDE4B and Akt, VSNL1 may affect cAMP signaling and neurite outgrowth in neurons. In dissociated rat hippocampal neurons, VILIP-1 small interfering RNA knockdown decreased cAMP levels and reduced dendrite branching, compared with control-transfected cells. In contrast, VILIP-1 overexpression had the opposite effect. Similar results have been obtained in the human dopaminergic neuronal cell line SH-SY5Y, where the effect on neurite branching and length was attenuated by the adenylyl cyclase inhibitor 2′,5′-dideoxyadenosine and the protein kinase A inhibitor KT5720. These results show that the association of VSNL1 SNPs with the disease and cognitive impairments, together with previously observed pathological changes in VILIP-1 protein expression, possibly occurring during brain development, may contribute to the morphological and functional deficits observed in schizophrenia. |
format | Online Article Text |
id | pubmed-3309514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-33095142012-04-03 Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology Braunewell, K H Dwary, A D Richter, F Trappe, K Zhao, C Giegling, I Schönrath, K Rujescu, D Transl Psychiatry Original Article We report an association of single-nucleotide polymorphisms (SNPs) for the VSNL1 gene (visinin-like 1) with schizophrenia and frontal cortical function in a sample of patients with Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) diagnoses of schizophrenia, compared with healthy controls. Moreover, VSNL1 SNPs were associated with performance in the Wisconsin Card Sorting Test, a measure for the assessment of frontal cortical function. The VSNL1 gene product, Visinin-like-protein-1 (VILIP-1), is a member of the neuronal EF-hand Ca(2+)-sensor protein family. Previously, VILIP-1 mRNA and protein expression were shown to be altered in animal models and in schizophrenia patients. VILIP-1 influences cytosolic cyclic adenosine mono phosphate (cAMP) levels, cell migration, exocytotic processes and differentiation in the periphery. This raises the question, whether, similar to other potential schizophrenia susceptibility genes such as Disc1, PDE4B and Akt, VSNL1 may affect cAMP signaling and neurite outgrowth in neurons. In dissociated rat hippocampal neurons, VILIP-1 small interfering RNA knockdown decreased cAMP levels and reduced dendrite branching, compared with control-transfected cells. In contrast, VILIP-1 overexpression had the opposite effect. Similar results have been obtained in the human dopaminergic neuronal cell line SH-SY5Y, where the effect on neurite branching and length was attenuated by the adenylyl cyclase inhibitor 2′,5′-dideoxyadenosine and the protein kinase A inhibitor KT5720. These results show that the association of VSNL1 SNPs with the disease and cognitive impairments, together with previously observed pathological changes in VILIP-1 protein expression, possibly occurring during brain development, may contribute to the morphological and functional deficits observed in schizophrenia. Nature Publishing Group 2011-07 2011-07-19 /pmc/articles/PMC3309514/ /pubmed/22832524 http://dx.doi.org/10.1038/tp.2011.20 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Braunewell, K H Dwary, A D Richter, F Trappe, K Zhao, C Giegling, I Schönrath, K Rujescu, D Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology |
title | Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology |
title_full | Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology |
title_fullStr | Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology |
title_full_unstemmed | Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology |
title_short | Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology |
title_sort | association of vsnl1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of camp levels and neuronal morphology |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309514/ https://www.ncbi.nlm.nih.gov/pubmed/22832524 http://dx.doi.org/10.1038/tp.2011.20 |
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