LÓPEZ-MOLINA, Laura; SANCHO-BALSELLS, Anna; AL-MASSADI, Omar; MONTALBAN, Enrica; ALBERCH, Jordi; ARRANZ, Belén; GIRAULT, Jean-Antoine; GIRALT, Albert

doi:10.1016/j.nbd.2024.106487

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Article de revue

Ce document a été publié dans

Neurobiology of Disease. 2024-03, vol. 194, p. 106487

Résumé en anglais

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.< Réduire

Mots clés en anglais

Hippocampus

Psychosis

Social symptoms

URI

https://oskar-bordeaux.fr/handle/20.500.12278/205582

DOI

http://dx.doi.org/10.1016/j.nbd.2024.106487

Project ANR

US-French Collaboration- Spatial and temporal aspects of molecular signaling in synaptic plasticity - ANR-15-NEUC-0002
Pyk2, synapses et maladie d'Alzheimer - ANR-19-CE16-0020

Unités de recherche

NutriNeuro (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286

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Hippocampal Pyk2 regulates specific social skills: Implications for schizophrenia