Figure 2:

MTX chemotherapy exposure disrupts oligodendrocyte lineage cell dynamics

A) Schematic illustration of juvenile MTX exposure paradigm and area of the premotor (M2) circuit analyzed (shaded in grey)

B) Total cell density of newly proliferated EdU⁺/PDGFRα⁺ cells at P63 in the corpus callosum of mice exposed to PBS or MTX on P21, 28, and 35 and injected with 40 mg/kg of EdU on P61, 62, and 63 (p=0.0465; n=4 mice/group)

C) Schematic illustration of oligodendrocyte lineage cells. OPCs express PDGFRα and begin to express the transcription factor Olig1 in a nuclear and then perinuclear pattern as they progress through differentiation. As differentiation completes, mature, myelinating oligodendrocytes express the marker CC1.

D-F) Effect of MTX exposure on OPCs (D; PDGFRα⁺ cells p<0.0001), PDGFRα⁺/Olig1⁺ late OPCs (E; p=0.0003) and CC1⁺ mature oligodendrocytes (F; p<0.0001) in the corpus callosum at P63 (n=8 mice PBS and n=7 mice MTX)

G-I) Photomicrographs of PDGFRα⁺ OPC (G), late PDGFRα⁺/Olig1⁺ cells (H) and CC1⁺ mature oligodendrocyte (I)

J-L) Mice (n=6 PBS; n=7 MTX) exposed to juvenile chemotherapy were allowed to age 6 months (P203) post-treatment. MTX-exposed mice exhibit a decrease in white matter OPC cell density (J; p=0.002) and CC1⁺ oligodendrocytes (L; p=0.008) with an increase in late OPCs (K; p=0.003).

Data shown as mean±SEM, * p<0.05, ** p<0.01, *** p<0.001 by unpaired two-tailed Student’s t-test; Scale bar=10 μm. See also Figure S1 and S2