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Delayed postnatal brain development and ontogenesis of behavior and cognition in a mouse model of intellectual disability

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  • Additional Information
    • Contributors:
      Institut des Neurosciences Paris-Saclay (NeuroPSI); Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS); LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS); Service Hospitalier Frédéric Joliot (SHFJ); Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
    • Publication Information:
      HAL CCSD
      Elsevier
    • Publication Date:
      2023
    • Collection:
      HAL-CEA (Commissariat à l'énergie atomique et aux énergies alternatives)
    • Abstract:
      International audience ; Intellectual disability (ID) is a neurodevelopmental disorder associated with impaired cognitive and adaptive behaviors and represents a major medical issue. Although ID-patients develop behavioral problems and are diagnosed during childhood, most behavioral studies in rodent models have been conducted in adulthood, missing precocious phenotypes expressed during this critical time-window characterized by intense brain plasticity. Here, we selectively assessed postnatal ontogenesis of behavioral and cognitive processes, as well as postnatal brain development in the male Rsk2-knockout mouse model of the Coffin-Lowry syndrome, an X-linked disorder characterized by ID and neurological abnormalities. While Rsk2-knockout mice were born healthy, a longitudinal MRI study revealed a transient secondary microcephaly and a persistent reduction of hippocampal and cerebellar volumes. Specific behavioral parameters from postnatal day 4 (P4) unveiled delayed acquisition of sensory-motor functions and alterations of spontaneous and cognitive behaviors during adolescence, which together, represent hallmarks of neurodevelopmental disorders. Together, our results suggest for the first time that RSK2, an effector of the MAPK signaling pathways, plays a crucial role in brain and cognitive postnatal development. This study also provides new relevant measures to characterize postnatal cognitive development of mouse models of ID and to design early therapeutic approaches.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/37270162; hal-04173450; https://cnrs.hal.science/hal-04173450; https://cnrs.hal.science/hal-04173450/document; https://cnrs.hal.science/hal-04173450/file/Delayed-postnatal-brain-development-ontogenesis-0-S096999612300178X.pdf; PUBMED: 37270162
    • Accession Number:
      10.1016/j.nbd.2023.106163
    • Online Access:
      https://cnrs.hal.science/hal-04173450
      https://cnrs.hal.science/hal-04173450/document
      https://cnrs.hal.science/hal-04173450/file/Delayed-postnatal-brain-development-ontogenesis-0-S096999612300178X.pdf
      https://doi.org/10.1016/j.nbd.2023.106163
    • Rights:
      http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
    • Accession Number:
      edsbas.93544E8A