Chronic Expression of PPAR-δ by Oligodendrocyte Lineage Cells in the Injured Rat Spinal Cord

The transcription factor peroxisome proliferator-activated receptor (PPAR)-delta promotes oligodendrocyte differentiation and myelin formation in vitro and is prevalent throughout the brain and spinal cord. Its expression after injury, however, has not been examined. Thus, we used a spinal contusion model to examine the spatiotemporal expression of PPAR-delta in naive and injured spinal cords from adult rats. As previously reported, PPAR-delta was expressed by neurons and oligodendrocytes in uninjured spinal cords; PPAR-delta was also detected in NG2 cells (potential oligodendrocyte progenitors) within the white matter and gray matter. After spinal cord injury (SCI), PPAR-delta mRNA and protein were present early and increased over time. Overall PPAR-delta+ cell numbers declined at 1 day post injury (dpi), likely reflecting neuron loss, and then rose through 14 dpi. A large proportion of NG2 cells expressed PPAR-delta after SCI, especially along lesion borders. PPAR-delta+ NG2 cell numbers were significantly higher than naive by 7 dpi and remained elevated through at least 28 dpi. PPAR-delta+ oligodendrocyte numbers declined at 1 dpi and then increased over time such that >20% of oligodendrocytes expressed PPAR-delta after SCI compared with similar to 10% in uninjured tissue. The most prominent increase in PPAR-delta+ oligodendrocytes was along lesion borders where at least a portion of newly generated oligodendrocytes (bromode-oxyuridine+) were PPAR-delta+. Consistent with its role in cellular differentiation, the early rise in PPAR-delta+ NG2 cells followed by an increase in new PPAR-delta+ oligodendrocytes suggests that this transcription factor may be involved in the robust oligodendrogenesis detected previously along SCI lesion borders. J. Comp. Neurol. 518:785-799, 2010. (C) 2009 Wiley-Liss, Inc.