Amelioration of Amyotrophic Lateral Sclerosis in SOD1G93A Mice by M2 Microglia from Transplanted Marrow

Abstract

Background/Aim: The cause of fatal neuromuscular amyotrophic lateral sclerosis (ALS) is not known. Materials and Methods: Ninety-day-old superoxide-dismutase-1 ^G93A (SOD1 ^G93A ) mice demonstrating level 1 paralysis, received 9.0 Gy total body irradiation (TBI) from a cesium source at 340 cGy per minute, and intravenous transplantation with 1×10 ⁶ C57BL/6 green fluorescent protein (GFP)+ donor bone marrow cells. Results: Paralysis-free survival was prolonged in TBI and bone marrow-transplanted SOD1 ^G93A mice from 100 to over 250 days (p=0.0018). Other mice transplanted with SOD1 ^G93A marrow or marrow treated with the free-radical scavenger MMS350 showed no therapeutic effect. GFP+ macrophage-2 (M₂) microglial cells of bone marrow origin, were seen at sites of degenerating anterior horn motor neurons. SOD1 ^G93A mice had a disruption in the blood-brain barrier permeability which was reversed by marrow transplant from C57BL/6 mice. SOD1 ^G93A marrow showed unexpected robust hematopoiesis in vitro, and radioresistance. Conclusion: After TBI, M₂ microglial cells from transplanted donor marrow extended the paralysis-free interval in SOD1 ^G93A mice.

Keywords: ALS; Total body irradiation; marrow origin; spinal cord M2 cells.