Changes in oligodendrocytes and myelin gene expression after radiation in the rodent spinal cord.

PURPOSE

The aim of this study was to assess changes in oligodendrocytes (OL), myelin gene expression, and their relationships with late demyelination after irradiation.

METHODS AND MATERIALS

Adult rats were given single doses of 8 or 22 Gy to the cervical spinal cord. Immunohistochemistry for APC or GST-pi was used to identify OL. Changes in myelin gene expression were assessed using RT-PCR for proteolipid protein (PLP). Luxol fast blue staining was used to assess demyelination. CNP-(beta)geo transgenic mice were used to confirm some of the results of the rat model. Cells of the oligodendroglial lineage in these animals express beta-galactosidase (beta-gal).

RESULTS

Early apoptosis of APC, GST-pi, and beta-galactosidase positive cells was observed in the spinal cord of rats and CNP-(beta)geo mice. At 24 h after 22 Gy, there was a significant decrease in OL density. Cell density continued to decline thereafter after both 8 and 22 Gy, and a reduction in PLP expression was observed at 4-5 weeks. A further decrease in PLP expression was seen beginning at 18 weeks after 22 Gy only. Demyelination was observed at 19 weeks after 22 Gy.

CONCLUSIONS

Apoptosis of OL and changes in OL density and PLP gene expression were observed early after both 8 and 22 Gy. This suggests that these early changes are unlikely to be directly related to the late demyelination observed.