The Journal of Neuroscience, March 15, 2000, 20(6):2218-2228

Proliferation and Differentiation of Progenitor Cells Throughout the Intact Adult Rat Spinal Cord
Philip J. Horner1, Ann E. Power2, Gerd Kempermann1, 3, H. Georg Kuhn3, Theo D. Palmer1, Jテδシrgen Winkler2, 3, Leon J. Thal2, and Fred H. Gage1

1テつ*The Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037,テつ*2テつ*Department of Neurosciences, University of California, San Diego, California 92093-0608,テつ*and 3テつ*Department of Neurology, University of Regensburg, 93053テつ*Regensburg, Germany

The existence of multipotent progenitor populations in the adult forebrain has been widely studied. To extend this knowledge to the adult spinal cord we have examined the proliferation, distribution, and phenotypic fate of dividing cells in the adult rat spinal cord. Bromodeoxyuridine (BrdU) was used to label dividing cells in 13-テつ*to 14-week-old, intact Fischer rats. Single daily injections of BrdU were administered over a 12テつ*d period. Animals were killed either 1テつ*d or 4テつ*weeks after the last injection of BrdU. We observed frequent cell division throughout the adult rodent spinal cord, particularly in white matter tracts (5-7% of all nuclei). The majority of BrdU-labeled cells colocalized with markers of immature glial cells. At 4テつ*weeks, 10% of dividing cells expressed mature astrocyte and oligodendroglial markers. These data predict that 0.75% of all astrocytes and 0.82% of all oligodendrocytes are derived from a dividing population over a 4テつ*week period. To determine the migratory nature of dividing cells, a single BrdU injection was given to animals that were killed 1テつ*hr after the injection. In these tissues, the distribution and incidence of BrdU labeling matched those of the 4テつ*week post injection (pi) groups, suggesting that proliferating cells divide in situ rather than migrate from the ependymal zone. These data suggest a higher level of cellular plasticity for the intact spinal cord than has previously been observed and that glial progenitors exist in the outer circumference of the spinal cord that can give rise to both astrocytes and oligodendrocytes.

Key words: spinal cord; progenitor; proliferation; rat; neurogenesis; stem cell; adult; gliogenesis