Hippocampal Pyk2 regulates specific social skills: Implications for schizophrenia
Por:
López-Molina L, Sancho-Balsells A, Al-Massadi O, Montalban E, Alberch J, Arranz B, Girault JA and Giralt A
Publicada:
1 may 2024
Ahead of Print:
1 mar 2024
Resumen:
Pyk2 has been shown previously to be involved in several psychological and cognitive alterations related to stress, Huntington's disease, and Alzheimer's disease. All these disorders are accompanied by different types of impairments in sociability, which has recently been linked to improper mitochondrial function. We hypothesize that Pyk2, which regulates mitochondria, could be associated with the regulation of mitochondrial dynamics and social skills. In the present manuscript, we report that a reduction of Pyk2 levels in mouse pyramidal neurons of the hippocampus decreased social dominance and aggressivity. Furthermore, social interactions induced robust Pyk2-dependent hippocampal changes in several oxidative phosphorylation complexes. We also observed that Pyk2 levels were increased in the CA1 pyramidal neurons of schizophrenic subjects, occurring alongside changes in different direct and indirect regulators of mitochondrial function including DISC1 and Grp75. Accordingly, overexpressing Pyk2 in hippocampal CA1 pyramidal cells mimicked some specific schizophrenia-like social behaviors in mice. In summary, our results indicate that Pyk2 might play a role in regulating specific social skills likely via mitochondrial dynamics and that there might be a link between Pyk2 levels in hippocampal neurons and social disturbances in schizophrenia.
Filiaciones:
López-Molina L:
Departament de Biomedicina, Facultat de Medicina, 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
Sancho-Balsells A:
Departament de Biomedicina, Facultat de Medicina, 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
Al-Massadi O:
Inserm UMR-S 1270, 75005 Paris, France
Sorbonne Université, Science and Engineering Faculty, 75005 Paris, France
Institut du Fer a Moulin, 75005 Paris, France
Translational Endocrinology Group, Servicio de Endocrinología, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago (IDIS/CHUS), Santiago de Compostela, Spain
CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Spain
Montalban E:
Inserm UMR-S 1270, 75005 Paris, France
Sorbonne Université, Science and Engineering Faculty, 75005 Paris, France
Institut du Fer a Moulin, 75005 Paris, France
UMR 1286, NutriNeuro - INRAE / Université de Bordeaux / INP 146, rue Léo Saignat, 33076 Brodeaux cedex, France
Alberch J:
Departament de Biomedicina, Facultat de Medicina, 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
Arranz B:
Parc Sanitari Sant Joan de Déu, CIBERSAM, Barcelona, Spain
Girault JA:
Inserm UMR-S 1270, 75005 Paris, France
Sorbonne Université, Science and Engineering Faculty, 75005 Paris, France
Institut du Fer a Moulin, 75005 Paris, France
Giralt A:
Departament de Biomedicina, Facultat de Medicina, 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. Electronic address: albertgiralt@ub.edu
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