Tracking New Myelin Formation during Adolescence and across the Lifespan of Mice
In periods of rapid growth and development, myelin-producing glial cells (oligodendrocytes, OLs) wrap lipid-rich myelin segments around axons, supporting fast communication across brain regions. White matter increases in frontotemporal brain regions during adolescence, corresponding with improvements in executive functioning, complex cognitive processing, and stress regulation. These functions are impacted early on in degenerative diseases like Alzheimer’s Disease, suggesting the integrity of white matter tracts interconnecting these regions may be impaired. It is therefore important to better understand the cellular dynamics of OLs during adolescence and the temporal and spatial patterns of new myelin formation during this critical developmental period. A major challenge in the field has been visualizing and tracking de novo myelin sheath formation. Herein we have successfully distinguished between new and previously formed myelin using a double transgenic conditional mouse reporter line (NG2-CreERt: Tau-mGFP). By combining this approach with triple immunofluorescent labeling and confocal imaging, we have discovered that there is rapid differentiation of OLs and formation of new myelin throughout frontotemporal white matter regions, including the anterior commissure, forceps minor of the corpus callosum, and the white matter tracts of the hippocampus and amygdala. Using CLARITY and light-sheet microscopy, we generated a 3D map of myelinated tracts formed during adolescence that remain in these frontotemporal regions well into adulthood. The cellular dynamics of OLs may change across the lifespan and affect myelin maintenance and the function of these frontotemporal circuits, leaving these pathways susceptible to degeneration. These findings could have significant implications for identifying targets and timelines of therapeutic intervention as individuals age.
Research Area | Presenter | Title | Keywords |
---|---|---|---|
Globalization and Development | Jain, Saniya | Development in India | |
Psychology and Behavioral Sciences | Tenney, Samantha Nicole | Development | |
Globalization and Development | Gray-Mullen, Niamh | Development | |
Public Health and Epidemiology | Tran, Caroline | Human Development | |
Psychology and Behavioral Sciences | Kanwal, Zarwah | Developmental change |