Proliferation of microglia/macrophages in the demyelinating CNS and PNS of twitcher mouse.

In demyelinating lesions in the central and peripheral nervous systems of twitcher mouse, a murine model of globoid cell leukodystrophy, marked increases of [3H]thymidine-labeled elements including Mac-1 immunopositive (Mac-1+) microglia/macrophages was observed. Their proliferative activities were already pronounced at the postnatal day (P) 20, an early stage of demyelination, peaked at P30 and then declined at P45, at the terminal stage of the disease. Many of the [3H]thymidine-labeled Mac-1+ cells had morphological features of ramified microglia. Macrophage-like Mac-1+ cells were less frequently labeled. The results of this study showed that (1) microglia/macrophages proliferated in the genetic demyelinating lesions, (2) many dividing Mac-1+ cells had the shape of ramified microglia and (3) the rate of proliferation declined in later stages when reactive microglia/macrophages were abundant in the lesions. The temporal events of this study suggest that signal(s) from the degenerating myelin or myelin-forming cells stimulate(s) cellular proliferation and that ramified microglia were one of the principal-dividing elements in the lesion. The biological mechanisms underlying the decline of the proliferative activity of microglia require further studies.