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Hippocampal Pyk2 regulates specific social skills: Implications for schizophrenia
Language
EN
Article de revue
This item was published in
Neurobiology of Disease. 2024-03, vol. 194, p. 106487
English 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 ...Read more >
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.Read less <
English Keywords
Hippocampus
Psychosis
Social symptoms
ANR Project
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
Pyk2, synapses et maladie d'Alzheimer - ANR-19-CE16-0020