Brain-wide structural and functional disruption in mice with oligodendrocyte-specific <i>Nf1</i> deletion is rescued by inhibition of nitric oxide synthase
Jad Asleh, Ben Shofty, Nadav Cohen, Alexandra Kavushansky, Alejandro López‐Juárez, Shlomi Constantini, Nancy Ratner, Itamar Kahn
Abstract
Significance This study assessed the effects of myelin decompaction on motor behavior and brain-wide structural and functional connectivity, and the effect of nitric oxide synthase inhibition by N -nitro- l -arginine methyl ester (L-NAME) on these imaging measures. We report that inducible oligodendrocyte-specific inactivation of the Nf1 gene, which causes myelin decompaction, results in reduced initial motor coordination. Using diffusion-based magnetic resonance imaging (MRI), we show reduced myelin integrity, and using functional MRI, we show reduced functional connectivity in awake passive mice. L-NAME administration results in rescue of the pathology at the mesoscopic level, as measured using imaging procedures that can be directly applied to humans to study treatment efficacy in clinical trials.