Lack of Helios During Neural Development Induces Adult Schizophrenia-Like Behaviors Associated With Aberrant Levels of the TRIF-Recruiter Protein WDFY1
Por:
Sancho-Balsells A, Brito V, Fernández B, Pardo M, Straccia M, Ginés S, Alberch J, Hernández I, Arranz B, Canals JM and Giralt A
Publicada:
14 may 2020
Categoría:
Cellular and molecular neuroscience
Resumen:
The role of the WDFY1 protein has been studied as a TLR3/4 scaffold/recruiting protein in the immune system and in different oncogenic conditions. However, its function in brain remains poorly understood. We have found that in mice devoid of Helios (He-/- mice), a transcription factor specifically expressed during the development of the immune cells and the central nervous system, there is a permanent and sustained increase of Wdfy1 gene expression in the striatum and hippocampus. Interestingly, we observed that WDFY1 protein levels were also increased in the hippocampus and dorsolateral prefrontal cortex of schizophrenic patients, but not in the hippocampus of Alzheimer's disease patients with an associated psychotic disorder. Accordingly, young He-/- mice displayed several schizophrenic-like behaviors related to dysfunctions in the striatum and hippocampus. These changes were associated with an increase in spine density in medium spiny neurons (MSNs) and with a decrease in the number and size of PSD-95-positive clusters in the stratum radiatum of the CA1. Moreover, these alterations in structural synaptic plasticity were associated with a strong reduction of neuronal NF-kappa B in the pyramidal layer of the CA1 in He-/- mice. Altogether, our data indicate that alterations involving the molecular axis Helios-WDFY1 in neurons during the development of core brain regions could be relevant for the pathophysiology of neuropsychiatric disorders such as schizophrenia.
Filiaciones:
Sancho-Balsells A:
Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Brito V:
Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Fernández B:
Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Pardo M:
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Science, University of Barcelona, Barcelona, Spain
Straccia M:
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Science, University of Barcelona, Barcelona, Spain
Faculty of Medicine and Health Science, Production and Validation Center of Advanced Therapies (Creatio), University of Barcelona, Barcelona, Spain
Ginés S:
Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Alberch J:
Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Faculty of Medicine and Health Science, Production and Validation Center of Advanced Therapies (Creatio), University of Barcelona, Barcelona, Spain
Hernández I:
Alzheimer Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades. Barcelona, Spain
Arranz B:
Parc Sanitari Sant Joan de Déu, CIBERSAM, Barcelona, Spain
Canals JM:
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Science, University of Barcelona, Barcelona, Spain
Faculty of Medicine and Health Science, Production and Validation Center of Advanced Therapies (Creatio), University of Barcelona, Barcelona, Spain
Giralt A:
Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Faculty of Medicine and Health Science, Production and Validation Center of Advanced Therapies (Creatio), University of Barcelona, Barcelona, Spain
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