White Matter Structural and Network Topological Changes Underlying the Behavioral Phenotype of MECP2 Mutant Monkeys

To explore the brain structural basis underlying the behavioral abnormalities associated with Rett syndrome (RTT), we carried out detailed longitudinal noninvasive magnetic resonance imaging analyses of RTT monkey models created by gene-editing, from weaning, through adolescence, till sexual maturation. Here, we report abnormal developmental dynamics of brain white matter (WM) microstructures and network topological organizations via diffusion tensor imaging. Specifically, disrupted WM microstructural integrity was observed at 9 months, but recovered thereafter, whereas WM network topological properties showed persistent abnormal dynamics from 9 to 37 months. Changes in the WM microstructure and WM network topology were correlated well with RTT-associated behavioral abnormalities including sleep latency, environmental exploration, and conflict encounters. Deleterious and protracted early WM myelination process likely lead to abnormal synaptic pruning, resulting in poor functional segregations. Together, this study provides initial evidence for changes in WM microstructure and network topological organization, which may underlie the neuro-patho-etilogy of RTT.

Automated summary

The study revealed that the brain white matter microstructure of Rett syndrome monkey models was initially disrupted but recovered later on, while the white matter network topology showed persistent abnormal dynamics, which were closely related to the behavioral abnormalities associated with RTT.