When the brain is injured in some way, a wide range of biochemical changes are triggered that can affect crucial brain cells known as astrocytes. They are a type of glial cell, and brain injuries cause reactive gliosis. While astrocytes were once thought of as cells that provide support to neurons, scientists have uncovered many critical functions of astrocytes. While reactive gliosis can indicate that central nervous system tissue is being repaired, it is also seen in neurodegenerative disease.
Scientists have now found a protein that seems to orchestrate reactive gliosis. The researchers suggested that this work may eventually help open new treatment options for a variety of neurodegenerative disorders. The research has been reported in Neuron.
"Reactive gliosis can help the nervous system adapt to stressful conditions to continue healthy functioning, but it can also be maladaptive, even causing neuronal death. Learning how to control this condition could help us protect cells from the negative aspects of reactive gliosis, changing the trajectory of neurodegenerative disease," explained senior study author Chun-Li Zhang, Ph.D., a Professor at UT Southwestern Medical Center.
The two most common glial cell types are astrocytes and microglia, and glia compose over half of the central nervous system's (CNS) volume. After a CNS injury, astrocytes and microglia proliferate, release restorative proteins, limit tissue damage, and protect the blood-brain barrier. These are signs of reactive gliosis. But this process can also interfere with the links, or synapses that connect neurons; it may disrupt the regeneration of parts of neurons called axons; or raise inflammation and increase cell death, noted Zhang. Many of these undesirable attributes of reactive gliosis are thought to be related to neurodegenerative disease.
In this work, the researchers analyzed a mouse model that had been exposed to a toxin that triggers inflammation. The investigators zeroed in on the mouse astrocytes, and identified a gene called Gadd45g, which significantly increased its activity after toxin exposure.
When healthy mice were engineered to have high Gadd45g activity, reactive gliosis was seen in astrocytes and in other adjacent cells. The researchers determined that the astrocytes were spreading reactive gliosis in other cells by releasing biochemical factors.
They also found that Gadd45g activity was usually high in a mouse model of Alzheimer's disease. When these mice were engineered to generate high levels of the GADD45G protein, their disease symptoms were much worse than in other mice that had not been altered in this way.
The gene is highly expressed in Alzheimer's patients as well.
The study concluded that Gadd45g is a master regulator of reactive gliosis.
It may also be possible to treat some neurodegenerative disorders by lowering GADD45G levels, but more research will be needed to confirm that hypothesis.
Sources: UT Southwestern Medical Center, Neuron