Tracking developmental connectopathy in 22q11.2 deletion syndrome with cross-species fMRI
Filomena Grazia Alvino1, Silvia Gini1, Alberto Galbusera1, David Sastre1, Federico Rocchi1, Marco Pagani1, Caterina Montani1, Francesco Papaleo2, Massimo Pasqualetti1,3, Carrie Bearden4, and Alessandro Gozzi1
1Italian Institute of Technology, Rovereto (TN), Italy, 2Italian Institute of Technology, Genova, Italy, 3Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy, 4Department of Psychiatry and Biobehavioral Sciences and psychology Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, United States
22q11.2 Deletion Syndrome (22q11DS), a major risk factor schizophrenia and autism, is often associated with disrupted brain connectivity. However, the developmental and neural underpinnings of brain connectopathy in 22q11DS remain unclear. Using mouse fMRI, we found that 22q11DS-related dysconnectivity exhibits a stereotypical developmental trajectory, with widespread functional hyperconnectivity in pre-pubertal mice reverting to focal fronto-hippocampal hypoconnectivity in adulthood. Notably, juvenile hyperconnectivity, but not adult hypoconnectivity, was completely rescued by a GSK3β antagonist. Finally, guided by our mouse model data, we identified a similar developmental trajectory in 22q11DS patients, hence corroborating the translational validity of these findings.
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