Summary: A new study sheds further light on the role astrocytes play in neurodegenerative disorders.
Source: University of Melbourne.
Astrocytes are shedding light on neurodegeneration caused by a range of diseases.
New research has shown how normally helpful brain cells can turn rogue and kill off other brain cells following injury or disease.
Astrocytes have long been implicated in the pathology of a range of human neurodegenerative diseases or injuries including Alzheimer’s, Huntington’s Parkinson’s disease, brain trauma and spinal cord injury.
But how they are produced and what their roles in disease may be, has been as yet unknown. This paper provides an understanding of the mechanism involved and for the first time provides hope that a lot of these diseases may in fact be treatable.
The study, published recently in Nature and led by researchers at The University of Melbourne and Stanford University, provides deeper understanding of the functions of injured or diseased astrocytes found in the Central Nervous System (CNS) following acute injury and chronic neurodegenerative disease.
In a healthy brain, astrocytes are vital for the normal functioning of the brain – providing nutrients to support neuron viability, releasing factors that aid formation of connections between nerve cells known as synapses, as well as many other important functions.
One puzzle has been that in some circumstances the astrocytes appear to have a toxic effect on neurons, whereas in others they support neuronal viability and connectivity.
Researcher Dr Shane Liddelow from the University of Melbourne’s Department of Pharmacology and Therapeutics,, and the Department of Neurobiology at Stanford University, said astrocytes are often characterised as ‘helper’ cells but they can also contribute to damage caused by brain injury and disease by turning toxic and kill other types of brain cells.
“These apparently opposing effects have been a puzzle for some time. By characterising two types of astrocytes this paper provides some answers to the puzzle,” he said.
“Following nerve damage, astrocytes form scar tissue that can help in the regeneration of severed fibres. But we have also discovered that under certain conditions, they can turn and become negatively reactive, causing cell death,” Dr Liddelow said
For many decades, the trauma and neurodegeneration research focus has been on neurons. Researchers are excited by the discovery of these neurotoxic reactive astrocytes, because for the first time, these findings imply that acute injuries of the retina, brain and spinal cord and chronic neurodegenerative diseases, may all be much more treatable and even reversible than first thought.
By providing new insights into the process of neurodegeneration, researchers can look at new pathways for dealing with neurological diseases and injuries, by targetting these toxic astrocytes, in addition to neurones in neuropsychiatric diseases or oligodendrocytes as for instance in multiple sclerosis.
Ultimately, there is still hope that one day it may be possible to switch back astrocytes from the “toxic” to the “helper” state, a long term target for Dr. Liddelow and colleagues.
Source: Elisabeth Lopez – University of Melbourne
Image Source: NeuroscienceNews.com image is credited to the researchers.
Original Research: Abstract for “Neurotoxic reactive astrocytes are induced by activated microglia” by 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 in Nature. Published online January 18 2017 doi:10.1038/nature21029
Neurotoxic reactive astrocytes are induced by activated microglia
Reactive astrocytes are strongly induced by central nervous system (CNS) injury and disease, but their role is poorly understood. Here we show that a subtype of reactive astrocytes, which we termed A1, is induced by classically activated neuroinflammatory microglia. We show that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A1 astrocytes. A1 astrocytes lose the ability to promote neuronal survival, outgrowth, synaptogenesis and phagocytosis, and induce the death of neurons and oligodendrocytes. Death of axotomized CNS neurons in vivo is prevented when the formation of A1 astrocytes is blocked. Finally, we show that A1 astrocytes are abundant in various human neurodegenerative diseases including Alzheimer’s, Huntington’s and Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis. Taken together these findings help to explain why CNS neurons die after axotomy, strongly suggest that A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders, and provide opportunities for the development of new treatments for these diseases.
“Neurotoxic reactive astrocytes are induced by activated microglia” by 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 in Nature. Published online January 18 2017 doi:10.1038/nature21029