Astrocytes role in brain injury and disease revealed

Astrocytes role in brain injury and disease revealed

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 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.

"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," author said.

Authors show that a subtype of reactive astrocytes, which we termed A1, is induced by classically activated neuroinflammatory microglia. They 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, authors 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.