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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) .

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Hippocampal Pyk2 regulates specific social skills: Implications for schizophrenia

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

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

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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.

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