Developmental myelination deficits and impaired fine motor function in a mouse model of pediatric obstructive sleep apnea.

STUDY

OBJECTIVES

Our primary objective was to characterize the mechanism that underlies fine motor deficits in Pediatric obstructive sleep apnea (POSA) using a preclinical mouse model of the disease. Our goal was to use a systematic approach to characterize neuroanatomical lesions in POSA mice and identify potential molecular drivers of the fine motor changes in this preclinical model of POSA.

METHODS

We used our established mouse model of POSA to characterize fine motor deficits using four approaches: a) neurobehavioral deficiencies in motor function with a focus on fine versus gross motor skills; b) resting state functional magnetic resonance imaging (rs-fMRI) as well as diffusion tension imaging (DTI); c) immunostaining of oligodendrocyte markers using a lineage tracing mouse, and d) the oligodendrocyte transcriptome using single-nucleus RNA sequencing.

RESULTS

POSA mice showed deficits in fine motor function without changes in gross motor function when compared with controls. DTI showed no significant differences between groups in gross motor tractography; however, rs-fMRI revealed region-to-region connection differences in POSA mice. Immunostaining showed fewer oligodendrocyte progenitor cells with no reduction in mature oligodendrocytes in POSA mice as compared to controls. The oligodendrocyte transcriptome in POSA mice identified many upregulated and downregulated genes involved in oligodendrocyte function and differentiation.

CONCLUSIONS

Consistent with neurological findings in POSA, these POSA mice showed deficits in fine motor skills. The molecular mechanism for the disruption of neuronal circuits involved the loss of developmental myelination, which may contribute to fine motor impairments in POSA.