Shane Liddelow & colleagues paper published in 26 January issue of Nature
Our congratulations to Shane who was in Professor Norman Saunders’ lab in the Department of Pharmacology and Therapeutics
Shane and his colleagues showed that neuroinflammation and ischaemia induced the formation of two different types of reactive astrocytes (induced by activated microglia) which they labelled A1 and A2. The A2 astrocytes upregulated a number of neurotrophic factors and they are postulated to be protective. By contrast, A1 astrocytes highly upregulated many of the classical complement cascade genes which have been shown to be destructive to synapses: A1 astrocytes are postulated to be harmful.
The authors were able to show that A1 astrocytes had lost most of their normal astrocytic functions and displayed neurotoxic activity capable of rapidly killing neurons and mature differentiated oligodendrocytes. Astrocytes are rapidly formed in vivo following CNS injury and were shown to be present in many human neurodegenerative diseases including Alzheimer’s, Huntington’s and Parkinson’s disease, as well as amyotrophic lateral sclerosis and multiple sclerosis. A1 astrocytes are thought to play an important role in the death of neurons and oligodendrocytes in these neurodegenerative diseases. Interventions that prevent A1 formation, or promote A1 reversion, or block the A1 neurotoxin, could lead to important new therapies in the treatment these diseases.
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017; 541: 481-487.