Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients
Neural adhesion proteins are crucial in the development and maintenance of functional neural connectivity. Growing evidence suggests that the IgLON family of neural adhesion molecules LSAMP, NTM, NEGR1, and OPCML are important candidates in forming the susceptibility to schizophrenia (SCZ). IgLON pr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Molecular Neuroscience |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00008/full |
| _version_ | 1819180666514833408 |
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| author | Karina Karis Karina Karis Kattri-Liis Eskla Kattri-Liis Eskla Maria Kaare Maria Kaare Karin Täht Jana Tuusov Jana Tuusov Tanel Visnapuu Tanel Visnapuu Jürgen Innos Jürgen Innos Mohan Jayaram Mohan Jayaram Tõnis Timmusk Cynthia S. Weickert Cynthia S. Weickert Marika Väli Marika Väli Eero Vasar Eero Vasar Mari-Anne Philips Mari-Anne Philips |
| author_facet | Karina Karis Karina Karis Kattri-Liis Eskla Kattri-Liis Eskla Maria Kaare Maria Kaare Karin Täht Jana Tuusov Jana Tuusov Tanel Visnapuu Tanel Visnapuu Jürgen Innos Jürgen Innos Mohan Jayaram Mohan Jayaram Tõnis Timmusk Cynthia S. Weickert Cynthia S. Weickert Marika Väli Marika Väli Eero Vasar Eero Vasar Mari-Anne Philips Mari-Anne Philips |
| author_sort | Karina Karis |
| collection | DOAJ |
| description | Neural adhesion proteins are crucial in the development and maintenance of functional neural connectivity. Growing evidence suggests that the IgLON family of neural adhesion molecules LSAMP, NTM, NEGR1, and OPCML are important candidates in forming the susceptibility to schizophrenia (SCZ). IgLON proteins have been shown to be involved in neurite outgrowth, synaptic plasticity and neuronal connectivity, all of which have been shown to be altered in the brains of patients with the diagnosis of schizophrenia. Here we optimized custom 5′-isoform-specific TaqMan gene-expression analysis for the transcripts of human IgLON genes to study the expression of IgLONs in the dorsolateral prefrontal cortex (DLPFC) of schizophrenic patients (n = 36) and control subjects (n = 36). Uniform 5′-region and a single promoter was confirmed for the human NEGR1 gene by in silico analysis. IgLON5, a recently described family member, was also included in the study. We detected significantly elevated levels of the NEGR1 transcript (1.33-fold increase) and the NTM 1b isoform transcript (1.47-fold increase) in the DLPFC of schizophrenia patients compared to healthy controls. Consequent protein analysis performed in male subjects confirmed the increase in NEGR1 protein content both in patients with the paranoid subtype and in patients with other subtypes. In-group analysis of patients revealed that lower expression of certain IgLON transcripts, mostly LSAMP 1a and 1b, could be related with concurrent depressive endophenotype in schizophrenic patients. Additionally, our study cohort provides further evidence that cannabis use may be a relevant risk factor associated with suicidal behaviors in psychotic patients. In conclusion, we provide clinical evidence of increased expression levels of particular IgLON family members in the DLPFC of schizophrenic patients. We propose that alterations in the expression profile of IgLON neural adhesion molecules are associated with brain circuit disorganization in neuropsychiatric disorders, such as schizophrenia. In the light of previously published data, we suggest that increased level of NEGR1 in the frontal cortex may serve as molecular marker for a wider spectrum of psychiatric conditions. |
| first_indexed | 2024-12-22T22:17:58Z |
| format | Article |
| id | doaj.art-69dc63800dbd487c96827942a578c24e |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-22T22:17:58Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-69dc63800dbd487c96827942a578c24e2022-12-21T18:10:44ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-01-011110.3389/fnmol.2018.00008324377Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic PatientsKarina Karis0Karina Karis1Kattri-Liis Eskla2Kattri-Liis Eskla3Maria Kaare4Maria Kaare5Karin Täht6Jana Tuusov7Jana Tuusov8Tanel Visnapuu9Tanel Visnapuu10Jürgen Innos11Jürgen Innos12Mohan Jayaram13Mohan Jayaram14Tõnis Timmusk15Cynthia S. Weickert16Cynthia S. Weickert17Marika Väli18Marika Väli19Eero Vasar20Eero Vasar21Mari-Anne Philips22Mari-Anne Philips23Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, EstoniaCentre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, EstoniaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, EstoniaCentre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, EstoniaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, EstoniaCentre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, EstoniaInstitute of Psychology, University of Tartu, Tartu, EstoniaDepartment of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, EstoniaEstonian Forensic Science Institute, Tallinn, EstoniaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, EstoniaCentre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, EstoniaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, EstoniaCentre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, EstoniaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, EstoniaCentre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, EstoniaDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, EstoniaFaculty of Medicine, School of Psychiatry, University of New South Wales, Sydney, NSW, AustraliaSchizophrenia Research Institute, Neuroscience Research Australia, Randwick, NSW, AustraliaDepartment of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, EstoniaEstonian Forensic Science Institute, Tallinn, EstoniaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, EstoniaCentre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, EstoniaDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, EstoniaCentre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, EstoniaNeural adhesion proteins are crucial in the development and maintenance of functional neural connectivity. Growing evidence suggests that the IgLON family of neural adhesion molecules LSAMP, NTM, NEGR1, and OPCML are important candidates in forming the susceptibility to schizophrenia (SCZ). IgLON proteins have been shown to be involved in neurite outgrowth, synaptic plasticity and neuronal connectivity, all of which have been shown to be altered in the brains of patients with the diagnosis of schizophrenia. Here we optimized custom 5′-isoform-specific TaqMan gene-expression analysis for the transcripts of human IgLON genes to study the expression of IgLONs in the dorsolateral prefrontal cortex (DLPFC) of schizophrenic patients (n = 36) and control subjects (n = 36). Uniform 5′-region and a single promoter was confirmed for the human NEGR1 gene by in silico analysis. IgLON5, a recently described family member, was also included in the study. We detected significantly elevated levels of the NEGR1 transcript (1.33-fold increase) and the NTM 1b isoform transcript (1.47-fold increase) in the DLPFC of schizophrenia patients compared to healthy controls. Consequent protein analysis performed in male subjects confirmed the increase in NEGR1 protein content both in patients with the paranoid subtype and in patients with other subtypes. In-group analysis of patients revealed that lower expression of certain IgLON transcripts, mostly LSAMP 1a and 1b, could be related with concurrent depressive endophenotype in schizophrenic patients. Additionally, our study cohort provides further evidence that cannabis use may be a relevant risk factor associated with suicidal behaviors in psychotic patients. In conclusion, we provide clinical evidence of increased expression levels of particular IgLON family members in the DLPFC of schizophrenic patients. We propose that alterations in the expression profile of IgLON neural adhesion molecules are associated with brain circuit disorganization in neuropsychiatric disorders, such as schizophrenia. In the light of previously published data, we suggest that increased level of NEGR1 in the frontal cortex may serve as molecular marker for a wider spectrum of psychiatric conditions.http://journal.frontiersin.org/article/10.3389/fnmol.2018.00008/full |
| spellingShingle | Karina Karis Karina Karis Kattri-Liis Eskla Kattri-Liis Eskla Maria Kaare Maria Kaare Karin Täht Jana Tuusov Jana Tuusov Tanel Visnapuu Tanel Visnapuu Jürgen Innos Jürgen Innos Mohan Jayaram Mohan Jayaram Tõnis Timmusk Cynthia S. Weickert Cynthia S. Weickert Marika Väli Marika Väli Eero Vasar Eero Vasar Mari-Anne Philips Mari-Anne Philips Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients Frontiers in Molecular Neuroscience |
| title | Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients |
| title_full | Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients |
| title_fullStr | Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients |
| title_full_unstemmed | Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients |
| title_short | Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients |
| title_sort | altered expression profile of iglon family of neural cell adhesion molecules in the dorsolateral prefrontal cortex of schizophrenic patients |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00008/full |
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