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.
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.
Authors: Lei Shi; M Constance Linville; Elizabeth Iversen; Doris P Molina; Jessie Yester; Kenneth T Wheeler; Michael E Robbins; Judy K Brunso-Bechtold Journal: J Neurol Sci Date: 2009-07-21 Impact factor: 3.181