Astroglia: key player in neurodegeneration

Astrocytes under confocal microscopy. Credit: Oregon State University

While everyone has heard about neurons, the information transmitting cells in the nervous system, astroglia is for many a complete stranger. For a long time, these cell type was considered nothing more than space filling in the brain, and to only exist for the purpose of suporting neurons, but in recent times their role is being examined closely, and findings point out to a much bigger impact on brain function and dysfunction as previously thought.

A recent study by the Barres lab, has shown the important role astrocytes play in neuron degeneration. More specifically the role of a specific subset of astroglia, the A1 reactive type, which is derived from resting astrocytes in the presence of pro-inflammatory factors like TNF-1alpha, IL-10 alpha or C1q, whose production by microglia is increased in response to infection (bacterial origin). Their experiments showed that the combined effect of these 3 factors led to increased astrocyte transformation. In a sort of Jeckyl & Hyde transformation, the supporting effect of resting astrocytes turn into neuron toxicity. In an in vitro cell culture experiment with a certain retinal cell type (RGC), A1s were shown to affect the pruning of spines and synapse formation, thus affecting neuron functionality. Moreover, growing RGCs in presence of a medium highly concentratedon the substances produced by the A1 cells led to extensive neuron death, pointing towards A1s producing a neuro toxin. Next, the researchers showed that this lethal effect was also true for other neuron types, such as the motor neurons and dopaminergic neurons whose death is responsible of Parkinson’s disease, or oligodendrocites (a cell type that helps synaptic impulse transduction), whose death leads to diseases like multiple sclerosis.

A further finding supporting the toxic role of A1 astrocytes in neurodegeneration, analysis of post-mortem samples of patients of Parkinson’s disease,Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis showed that high numbers of A1 astrocytes accumulated in regions of active disease, such as the frontal cortex of Alzheimer’s patients, and given the deadly effects of A1 astrocytes both on neurons and oligodendrocytes, it seems that A1 cells are playing a key role in neurodegenerative diseases.

The identity of the neurotoxic substance produced by A1 astrocytes is yet unknown, and research efforts are being made to find it as soon as possible given the potential of this factor in the design of drugs useful in the management of many neurodegenerative diseases. Meanwhile, it is important to acknowledge the relevance of this finding, which once again shows how far we are from a real understanding of the nervous system. Amazing complex thing our brain, isn’t it?

 

Shane A. Liddelow, Kevin A. Guttenplan, Laura E. Clarke, Frederick C. Bennett, Christopher J. Bohlen, Lucas Schirmer, Mariko L. Bennett, Alexandra E. Münch, Won-Suk Chung, Todd C. Peterson, Daniel K. Wilton, Arnaud Frouin, Brooke A. Napier, Nikhil Panicker, Manoj Kumar, Marion S. Buckwalter, David H. Rowitch, Valina L. Dawson, Ted M. Dawson, Beth Stevens, Ben A. Barres. Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 541,481–487 (2017)

 

Further reading:

Liddelow, S. & Barres, B. SnapShot: astrocytes in health and disease. Cell 162, 11701170.e1 (2015)

Stephan, A. H. et al. A dramatic increase of C1q protein in the CNS during normal aging. J. Neurosci. 33, 1346013474 (2013)

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