Loss of Adaptive Myelination Contributes to Methotrexate Chemotherapy-Related Cognitive Impairment.

ABSTRACT: Activity-dependent myelination is thought to contribute to adaptive neurological function. However, the mechanisms by which activity regulates myelination and the extent to which myelin plasticity contributes to non-motor cognitive functions remain incompletely understood. Using a mouse model of chemotherapy-related cognitive impairment (CRCI), we recently demonstrated that methotrexate (MTX) chemotherapy induces complex glial dysfunction for which microglial activation is central. Here, we demonstrate that remote MTX exposure blocks activity-regulated myelination. MTX decreases cortical Bdnf expression, which is restored by microglial depletion. Bdnf-TrkB signaling is a required component of activity-dependent myelination. Oligodendrocyte precursor cell (OPC)-specific TrkB deletion in che

SUBMITTER: Geraghty AC 

PROVIDER: S-EPMC6697075 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature