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

• DOI: 10.1016/j.nbd.2023.106163
• Publication Date: 2023-06-01T19:55:16Z
• Authors: Laurine Gonzalez; Catherine Sébrié; Serge Laroche; Cyrille Vaillend; Roseline Poirier
• Keywords: Microcephaly; Neurodevelopmental disorder; Knockout mouse

Intellectual disability (ID) is a neurodevelopmental disorder associated with impaired cognitive and adaptive behaviors represents major medical issue. Although ID-patients develop behavioral problems are diagnosed during childhood, most studies in rodent models have been conducted adulthood, missing precocious phenotypes expressed this critical time-window characterized by intense brain plasticity. Here, we selectively assessed postnatal ontogenesis of processes, as well development the male Rsk2-knockout mouse model Coffin-Lowry syndrome, an X-linked ID neurological abnormalities. While mice were born healthy, longitudinal MRI study revealed transient secondary microcephaly persistent reduction hippocampal cerebellar volumes. Specific parameters from day 4 (P4) unveiled delayed acquisition sensory-motor functions alterations spontaneous adolescence, which together, represent hallmarks disorders. Together, our results suggest for first time that RSK2, effector MAPK signaling pathways, plays crucial role development. This also provides new relevant measures to characterize design early therapeutic approaches.