According to researchers at Johns Hopkins, a protein created by the central nervous system’s support cells (glia) appears to protect nerve cells from damage in two different ways. The study is published in Proceedings of the National Academy of Sciences (PNAS).
Reducing the proteins activity appears to trigger glia cells to increase their protective powers. However, the team found that increasing its activity seems to be vital for using those powers to protect cells from danger.
Glia cells have long been thought to play a vital role in protecting cells from death after an acute injury, such as a blow to the head, or chronic damage, such as that cause by Parkinson’s or Alzheimer’s disease, according to Seth Blackshaw, Ph.D., an associate professor in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine.
For several decades, glia cells were thought to help hold the central nervous system together. When nearby neurons are exposed to an assault, glia cells respond by increasing in size and switching off several genes involved in routine maintenance functions.
According to earlier studies, when glia cells and neurons are exposed to an assault, the reaction of the glia appeared to power a response that protects cells from further damage. However, what glia cells are doing when they change in size and gene expression and whether this response is vital for protection remains unclear, states Blackshaw.
Blackshaw notes that it has been impossible for researchers to investigate this so-called glial reactivity without treating whole tissues that include neurons and other types of cells that may apply their own protective effects.
As a result, the researchers set out to identify proteins that could play a vital role in triggering glial reactivity without assaulting entire tissues.
In the study the researchers used Mueller glia as their model system as they are extremely likely to act like other glia throughout the central nervous system. These glia are the most abundant type in the retina.
The team identified a protein called Lhx2. In mutant mice that selectively lacked Lhx2 in the glia of the eye, the team found that these cells showed the physical and genetic characteristics of being constantly reactive, even without any damaging stimulus. However, they discovered that shinning an extremely bright light into the into the animals eyes caused significantly more damage to their retinas than in normal mice.
In order to determine why these reactive glia didn’t produce a protective response, the team set out to identify other pro-survival proteins that glia cells produce when under attack. These other proteins were missing in the mutant mice, thus indicating that Lhx2 is vital for glia to produce other protective proteins, said Blackshaw.
Blackshaw explained: “Lhx2 seems to be a master regulator of glial reactivity, and we’ve shown here that it has two faces.”
Although the absence of Lhx2 appears to be vital for stimulating the physical and genetic changes glia use to protect and help neurons survive, the presence of Lhx2 is crucial for production of these proteins in the first place.
According to Blackshaw, when glia is exposed to an attack, levels of Lhx2 activity likely drop and then increase, explaining both the initial glial reactivity researchers see under a microscope as well as the resulting neural protection.
Once this mechanism is understood better, researchers may be able to develop drugs that trigger glia to generate more pro-survival proteins, creating new treatments for neurodegenerative diseases, said Blackshaw.
Written By Grace Rattue