Ablation of proliferating cells in the CNS exacerbates motor neuron disease caused by mutant superoxide dismutase

Abstract

Proliferation of glia and immune cells is a common pathological feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Here, to investigate the role of proliferating cells in motor neuron disease, SOD1 G93A transgenic mice were treated intracerebroventicularly (ICV) with the anti-mitotic drug cytosine arabinoside (Ara-C). ICV delivery of Ara-C accelerated disease progression in SOD1 G93A mouse model of ALS. Ara-C treatment caused substantial decreases in the number of microglia, NG2+ progenitors, Olig2+ cells and CD3+ T cells in the lumbar spinal cord of symptomatic SOD1 G93A transgenic mice. Exacerbation of disease was also associated with significant alterations in the expression inflammatory molecules IL-1β, IL-6, TGF-β and the growth factor IGF-1. © 2012 Audet et al.