Radioautographic investigation of gliogenesis in the corpus callosum of young rats II. Origin of microglial cells

Abstract

Microglial cells are absent from the corpus callosum of newborn rats. In the hope of finding out when and how microglial cells appear with age, 3H-thymidine was given intraperitoneally as single or three shortly spaced injections to 5-day-old rats weighing about 15 g; and these animals were sacrificed at various time intervals from 2 hours to 35 days later. Pieces of corpus callosum were taken near the superior lateral angle of the lateral ventricles; and semithin sections were radioautographed and stained with toluidine blue. The corpus callosum of 5-day-old rats is composed of loosely arranged unmyelinated fibers and scattered cells. Among these cells, microglia are rare; there are a few astrocytes, many immature glial cells, rare pericytes, and 6--7% of phagocytic "ameboid cells" consisting of a few monocytes and many macrophages. In the animals sacrificed two hours after 3H-thymidine administration, label is present only in immature cells and "ameboid cells." As time elapses and the fibers of corpus callosum become myelinated, oligodendrocytes and, later, microglial cells appear. At the age of 12 days, microglial cells are present in substantial number; and by 19 days, the number doubles to reach a plateau. Many of the new microglial cells are labeled, e.g., 78.1% in 12-day-old animals (7 days after 3H-thymidine administration). The labeled microglial cells must have come from the transformation of cells that acquired label early, that is, from the immature cells or the "ameboid cells." The height of the peaks of labeling--59.8% at nine days for immature cells and 77.8% at 12 days for "ameboid cells"--points to the latter as precursors of the highly labeled microglial cells. Furthermore, the "ameboid cells" disappear as microglial cells appear and there are transitional elements between these two cell types. Cell counts suggest that about a third of the "ameboid cells" transform into microglial cells, while the others degenerate and die. Thus, the microglial cells which appear in the corpus callosum during the first three weeks of life result from transformation of the "ameboid cells"--a group of macrophages showing various stages of transition from monocytes. As for the occasional microglial cell appearing after the third week or in the adult, they presumably come directly from monocytes. In either case, monocytes would be the initial precursors.

Vault immunofluorescence in the brain: new insights regarding the origin of microglia

“…Mori and Leblond (1969) suggested that pericytes could be one source of microglia based upon their observation of silver carbonate-stained cells on the capillary wall that resembled microglia in morphology. A number of other investigators have subsequently lent support to this notion (Baron and Gallego, 1972;Brichova, 1972;Sturrock, 1974;Hager, 1975;Boya, 1976), though Imamoto and Leblond (1978) reported they could find no evidence that pericytes migrated into brain tissue.…”

Transformation of amoeboid microglial cells into microglia in the corpus callosum of the postnatal rat brain. An electron microscopical study.

“…The rough endoplasmic reticulum (arrows) is present in single isolated profiles. x 10,500 the hypothesis of the transformation of amoeboid microglia into microglia (Rio-HORTEGA, 1932;KERSHMAN, 1939;IMAMOTO and LEBLOND, 1978;LING, 1981;1MAMOTO et al, 1982).…”

“…The small microglial cells described by MORI and LEBLOND (1969) in adult animals, however, are negligible in number or virtually absent during this period as they first appear about the 5th postnatal day (ZING and TAN, 1974;IMAMOTO and LEBLOND, 1978). Soon after their appearance, their number increases steadily with age (ZING and TAN, 1974) so that by weaning age, they form about 5°0 of the total glial population and their total number remains fairly constant thereafter (ZING and LEBLOND,1973).…”

Perspectives of Stem Cell-Derived Microglia for Medicine

“…This view was further supported by the discovery that the first appearance of microglial cells coincide with the vascularization of the brain. It was suggested that circulating monocytes enter the nervous system and transform to microglia (Imamoto and Leblond, 1978;Ling, 1979) before the formation of the blood-brain-barrier has been completed (Perry et al, 1985). Infiltration of monocytes could be confirmed by carbon-labelling (Ling et al, 1980) and histochemical studies using marker enzymes for monocytes (Ferrer and Sarmiento, 1980;Ling et al, 1982).…”