Developmental changes in myelin-induced proliferation of cultured Schwann cells.

Abstract

Abstract. Schwann cell proliferation induced by a myelin-enriched fraction was examined in vitro. Although nearly all the Schwann cells contained material that was recognized by antisera to myelin basic protein after 24 h, only 1% of the cells were synthesizing DNA. 72 h after the addition of the mitogen a maximum of 10% of the cells incorporated [3H]thymidine. If the cultures were treated with the myelin-enriched fraction for 24 h and then washed, the number of proliferating Schwann cells decreased by 75 % when compared with those cells that were incubated with the mitogen continuously. When Schwann cells were labeled with [~C]thymidine followed by a pulse of [3H]thymidine 24 h later, every Schwann cell labeled with [3H]thymidine was also labeled with [~4C]thymidine. Although almost every Schwann cell can metabolize the myelin membranes within 24 h of exposure, a small population of cell initially utilizes the myelin as a mitogen, and this population continues to divide only if myelin is present in the extracellular media. The percentage of the Schwann cells that initially recognize the myelinenriched fraction as a mitogen is dependent upon the age of the animal from which the cells were prepared. CULTURED Schwann cells proliferate when treated with axolemma-or myelin-enriched fractions (15). The mitogenic activities of the membrane fractions could be differentiated by their dose-response curves and their sensitivity to the lysosomal inhibitor, ammonium chloride. Also, the rates of [3H]thymidine incorporation by Schwann cells treated with the myelin-enriched fraction were not identical when compared with those cells incubated with the axolemmal membranes. Schwann cells that were exposed to the myelin-enriched fraction for 72 h accumulated three times as much [3H]thymidine as those that were incubated with the mitogen for only 48 h. This sudden increase in proliferation coincided temporarily with similar periods of Schwann cell division during Wallerian degeneration in vitro (14) and in vivo (4).In the present study, we have examined by autoradiography the kinetics of Schwann cell proliferation induced with a myelin-enriched fraction in vitro. The large increase in proliferation that occurs 72 h after the administration of the mitogen is the result of a small population of Schwann cells that initially divides in response to the mitogen and whose daughter cells subsequently continue to proliferate if the membrane fraction is present in the extracellular media. The number of Schwann ceils that divide initially when treated with the myelin-enriched fraction is related to the age of the animal from which the cells were prepared. Materials and MethodsHF ~ is DME (Gibco Laboratories, Grand Island, NY) with sodium bicarbonate and 10% FCS (HyClone Laboratories, Logan, UT). Saline G is a 1. Abbreviation used in this paper: HE DME with sodium bicarbonate and 10% FCS. balanced salt solution containing 125 mM NaCI, 5 mM KCI, 0.7 mM MgSO4, 0.1 mM CaCI2, 1 mM KH2PO4, and 1 mM Na2HPO4. Forskolin (Calbiochem-Behring Corp., La J...

The role of Schwann cells and macrophages in the removal of myelin during Wallerian degeneration.

“…Much evidence has shown that the digestive process of myelin is intimately related to Schwann cell proliferation (1,2,5,8,11,20,21). The removal of the myelin sheath elicited proliferative response of Schwann cells (5,12,16).…”

In vivo Proliferative Pattern of Trembler Hypomyelinating Schwann Cells Is Modified in Culture: An Experimental Analysis

“…lb) might then result from an increased level of mitogenic factors pro vided by the degrading myelin. A similar age-related in crease has also been described in myelin-induced pro liferation of rat Schwann cells [40]. Conversely, the low rate of Trembler Schwann cell division would be corre lated with the reduced amount of degradable myelin present in mutant nerves at the time they are plated.…”

“…The proliferation of secondary mouse quiescent Schwann cells started only 48 h after myelin was added to the medium, as shown in rat Schwann cell cultures [40]. At day 1, few nuclei were labeled.…”

“…Several studies have reported that brain and PNS MEF prepared from young rats were mitogenic for Schwann cells in culture [40,[48][49][50].…”

Pre‐degenerated nerve shows enhanced regeneration after incremental elongation in rats

“…After differentiation, Schwann cells phagocytize myelin debris. Lysosome-processed myelin debris then acts as an inducer and activator for resident macrophages [7,12,29]. Differentiated and activated Schwann cells and macrophages produce neurotrophic factors that accelerate axonal sprouting and outgrowth [21], while proliferating Schwann cells arrange themselves to form tubes to guide regenerating axons.…”