The magnitude of glial cell renewal was studied on young adult mice using repeated intraperitoneal injections of 3H-thymidine every eight hours over a period of 30 days. Mean labeling indices one hour after the last injection were as follows: Glial cells of the subependymal layer of the lateral ventricle, 61.5% ; oligodendrocytes (various sites), 24 to 36.2% ; astrocytes (various sites), 14.3 to 30.8%, and satellites in the cerebral cortex, 32.7%. Since DNA synthesis time of the proliferating, immature glial cells is unknown and may be shorter than the time interval of eight hours chosen for repeated injections of 3H-thymidine, these results are interpreted as representing minimum values for turnover, during 30 days, of the various cell types in different areas of the forebrain. The significance of a marked proliferative activity of the glial cells as related to differentiation and possible migration of subependymal cells, is discussed.Cellular proliferative activity in the intact mammalian brain has long been considered to decrease and cease in early postnatal life (Spielmeyer, '22; Penfield, '32). In the subependymal layer of the forebrain, however, mitotic activity persists in the adult animal (Allen, '12; Bryans, '59). The combined use in small rodents of radioactively labeled DNA precursors such as 3H-thymidine ( 3H-TdR) and autoradiography, confirms these findings and demonstrates the presence of DNA-synthesizing cells in the subependymal layer of young adult mice (Messier et al., '58; Smart and Leblond, '61; Noetzel and Rox, '64). A few initially labeled cells are also found in other regions of the brain (Smart and Leblond, '61). In all these studies, nerve cells do not incorporate the labeled DNA precursor.Continuous administration of 3H-TdR to pregnant rats results in complete labeling of the newborn. The labeling indices of astrocytes and oligodendrocytes in the cerebral cortex decrease progressively within five months after birth, indicating J. COMP. NEUR., 148: 211-216. definite turnover for these cells (Haas et al., '70). In this system, however, reutilization by proliferating cells of label from disintegrating elements may lead to an underestimate of the replacement rate. In order to obtain further information on the magnitude of glial cell turnover, young adult mice were given repeated injections of 3H-TdR. The percentage of labeled cells, the labeling intensity and the regional distribution of neuroglial cells in the forebrain were determined.
MATERIALS AND METHODSTwelve four week-old, female Swiss albino mice (Hale-Stoner strain) were studied. Thymidine-rneth~l-~H (Schwarz BioResearch, Inc. Orangeburg, N. Y.; specific activity 1.9 Ci/mmole) was diluted in isotonic saline to an activity of 16.7 ?Ci/ml, and 100 mg Na-Penicillin G per liter was added. Mice were injected intraperitoneally at a dose of 0.33 ,Ci per gm of body weight every eight hours, for