Document Type
Article
Publication Date
9-8-2020
Abstract
Neurofibromin gene (NF1) mutation causes neurofibromatosis type 1 (NF1), a disorder in which brain white matter deficits identified by neuroimaging are common, yet of unknown cellular etiology. In mice, Nf1 loss in adult oligodendrocytes causes myelin decompaction and increases oligodendrocyte nitric oxide (NO) levels. Nitric oxide synthase (NOS) inhibitors rescue this pathology. Whether oligodendrocyte pathology is sufficient to affect brain-wide structure and account for NF1 imaging findings is unknown. Here we show that Nf1 gene inactivation in adult oligodendrocytes (Plp-Nf1fl/+ mice) results in a motor coordination deficit. Magnetic resonance imaging in awake mice showed that fractional anisotropy is reduced in Plp-Nf1fl/+ corpus callosum and that interhemispheric functional connectivity in the motor cortex is also reduced, consistent with disrupted myelin integrity. Furthermore, NOS-specific inhibition rescued both measures. These results suggest that oligodendrocyte defects account for aspects of brain dysfunction in NF1 that can be identified by neuroimaging and ameliorated by NOS inhibition.
Recommended Citation
Asleh, J., Shofty, B., Cohen, N., Kavushansky, A., López-Juárez, A., Constantini, S., Ratner, N., & Kahn, I. (2020). Brain-wide structural and functional disruption in mice with oligodendrocyte-specific Nf1 deletion is rescued by inhibition of nitric oxide synthase. Proceedings of the National Academy of Sciences of the United States of America, 117(36), 22506–22513. https://doi.org/10.1073/pnas.2008391117
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
First Page
22506
Last Page
22513
Publication Title
PNAS
DOI
10.1073/pnas.2008391117
Comments
© 2020 the Author(s). Published by PNAS.