Microglia may turn some astrocytes against motor neurons and oligodendrocytes in ALS according to a study published on January 18 in Nature. The study, led by Ben Barres of Stanford University School of Medicine, found that a subset of astrocytes appeared to proliferate upon neuronal injury in vivo leading to degeneration of more than 60% of nearby neurons. What’s more, these cells appeared to inhibit the differentiation and proliferation of oligodendrocyte precursor cells (OPCs) and destroy oligodendrocytes, key cells that provide metabolic support to motor neurons that appear to be lost in the disease (see January 2011, April 2013 and November 2016 news; Lee et al., 2013). This astroglial about-face appeared to be instigated by reactive microglia due to the secretion of interleukin-1α, tumor necrosis factor (TNF) and complement C1q. The cells, called A1 astrocytes, could be detected in post mortem tissue from patients with five neurodegenerative diseases including ALS. The results suggest that this microglial-based attack strategy could be a key general underlying mechanism of neurodegenerative disease (see January 2017 news).
Researchers first suspected in 2011 that some astrocytes might go rogue in ALS by studying the G93A rat model of SOD1 disease. The study, led by Luis Barbeito at the Institut Pasteur de Montevideo in Uruguay, found that a subset of astrocyte-like cells appeared in the ventral horn of the spinal cord during symptom onset – surrounding damaged motor neurons. In addition, the numbers of these cells rose during disease progression – increasing more than 50% by the end stage of the disease. The cells, called aberrant astrocytes (ABAs), appeared to destroy motor neurons by secreting neurotoxic substances including connexin 43 – at least in culture.
Together, the results suggest these astrocytes may be a key contributor to ALS and targeting them may be a potential therapeutic strategy for the disease.
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