Table 1 |.
Approach | Advantages | Disadvantages |
---|---|---|
Tools to impair or prevent new oligodendrocyte differentiation | ||
OPC-specific Cre drivers (such as NG2-CreER or PDGFRα-CreER) to conditionally knock out key genes involved in myelination (creating Myrf cKOs or Olig2 cKOs, for example) | Allows cell type-specific manipulation; onset of impaired differentiation can be controlled by tamoxifen administration | Requires an OPC Cre driver; Myrf or Olig2 may have additional functions beyond regulation of differentiation; effect is not region-specific; does not differentiate between ongoing and experience-induced myelination |
Tools to enhance myelination | ||
Clemastine or bazedoxifene | Does not require Cre driver; simple to administer (systemic injection) | Not cell type or region-specific; may have unknown off-target effects |
OPC-specific Cre drivers (such as NG2-CreER or PDGFRα-CreER) to conditionally knock out M1R, a negative regulator of myelination (Chrm1 cKO) | Cell type-specific manipulation; onset of enhanced differentiation can be controlled by tamoxifen administration | Requires OPC Cre driver; M1R may have other effects beyond regulating differentiation; effect is not region-specific |
Methods to label new oligodendrocyte or myelin formation | ||
Use EdU or BrdU, together with immunostaining for PDGFRa or NG2 (OPCs), CC1 or ASPA (mature oligodendrocytes), or OLIG2 or SOX10 (oligodendrocyte lineage cells) | Does not require Cre driver; identifies OPCs, oligodendrocytes or oligodendrocyte lineage cells that arose from OPCs that proliferated after EdU or BrdU administration | Does not capture oligodendrocytes that directly differentiated without proliferating first; cannot visualize myelin sheaths |
OPC-specific Cre drivers (such as NG2-CreER or PDGFRα-CreER) to drive the expression of tau-mGFP | Captures newly formed oligodendrocytes and sheaths that arose from direct differentiation and from OPCs that first proliferated; allows for visualization of myelin sheaths | Requires OPC Cre driver; does not demonstrate the presence of bona fide compact myelin |
Expression of fluorescent proteins under the control of OPC-specific promoters (such as NG2-mEGFPorMOBP-EGFP) | Allows for in vivo visualization and tracking of OPCs and differentiated oligodendrocytes; allows for visualization of fine processes in both cell types | Requires in vivo longitudinal imaging to differentiate between existing and newly formed cells; does not demonstrate the presence of bona fide compact myelin |
ASPA, aspartoacylase; BrdU, 5-bromo-2′-deoxyuridine; cKO, conditional knockout; EdU, 5-ethynyl-2′-deoxyuridine; OPC, oligodendrocyte precursor cell.