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This work was supported by grants from the Ministerio de Ciencia e Innovacion/AEI/10.13039/501100011033/ and "FEDER": AG: PID2021-122258OB-I00; JA: PID2020-119386RB-100. OAM was funded by a Miguel Servet Research Contract (CP20/00146) from the ISCIII. We thank Ana Lopez and Maria Teresa Munoz (Maria de Maeztu Unit of Excellence, Institute of Neurosciences, University of Barcelona, CEX2021-001159-M, Ministry of Science and Innovation) for their technical support. We thank Maria Calvo from the Advanced Microscopy Service (Centres Cientifics i Tecnologics Universitat de Barcelona) for her help in the acquisition, analysis, and interpretation of the confocal microscopy images. Work in the lab of JAG was supported by grants from the Agence Nationale de la Recherche (ANR-15-NEUC-0002-02 and ANR-19-CE16-0020) and from the Fondation pour la recherche medicale (FRM, EQU201903007844) .

Analysis of institutional authors

Lopez-Molina, LauraCorresponding AuthorSancho-Balsells, AnnaAuthorAlberch, JordiAuthorGiralt, AlbertCorresponding Author

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August 25, 2024
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Hippocampal Pyk2 regulates specific social skills: Implications for schizophrenia

Publicated to:Neurobiology Of Disease. 194 106487- - 2024-05-01 194(), DOI: 10.1016/j.nbd.2024.106487

Authors: López-Molina, L; Sancho-Balsells, A; Alberch, J; Giralt, A; Al-Massadi, O; Montalban, E; Girault, JA; Arranz, B

Affiliations

CIBER Fisiopatol Obesidad & Nutr CIBERobn, Madrid, Spain - Author
CIBERSAM, Parc Sanitari St Joan de Deu, Barcelona, Spain - Author
Complexo Hosp Univ Santiago IDIS CHUS, Inst Invest Sanitaria Santiago de Compostela, Serv Endocrinol, Translat Endocrinol Grp, Santiago De Compostela, Spain - Author
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain - Author
INSERM, UMR S 1270, F-75005 Paris, France - Author
Inst Fer Moulin, F-75005 Paris, France - Author
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain - Author
Sorbonne Univ, Sci & Engn Fac, F-75005 Paris, France - Author
Univ Barcelona, Inst Neurociencies, Fac Med, Dept Biomed, Barcelona 08036, Spain - Author
Univ Barcelona, Prod & Validat Ctr Adv Therapies Creatio, Fac Med & Hlth Sci, Barcelona, Spain - Author
Univ Bordeaux, INRAE, UMR 1286, NutriNeuro,INP 146, Rue Leo Saignat, F-33076 Brodeaux, France - Author
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Abstract

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.

Keywords

AbnormalitiesActivationAggressivenessAnimalAnimal experimentAnimal tissueAnimalsAnxietyArticleAstrocytesCohort analysisControlled studyDisorderDisrupted in schizophrenia 1 proteinDysfunctionElevated plus maze testExpressionFocal adhesion kinase 2Glucose regulated proteinGlucoseregulated protein 75Hippocampal ca1 regionHippocampusHumanHuman tissueHumansKinaseMaleMetabolismMiceMitochondriaMitochondrial dynamicsMouseNegative symptomsNonhumanOpen field testOxidative phosphorylationPhenotypePhosphorylationPsychosisPyramidal cellsPyramidal nerve cellSchizophreniaSensory gatingSocial competenceSocial dominanceSocial interactionSocial skillsSocial symptomSocial symptomsUnclassified drug

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal NEUROBIOLOGY OF DISEASE due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 48/310, thus managing to position itself as a Q1 (Primer Cuartil), in the category Neurosciences.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-16:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 14.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 19 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 3.95.
  • The number of mentions on the social network X (formerly Twitter): 7 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: France.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (López Molina, Laura) and Last Author (Giralt Torroella, Albert).

the authors responsible for correspondence tasks have been López Molina, Laura and Giralt Torroella, Albert.