According to new research performed in rodents, cells that usually nurture nerves may actually destroy them following a brain injury.
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This “reactive” phenomenon could be the main factor behind neurodegenerative disorders like glaucoma—a major cause of blindness.
Headed by scientists from NYU Grossman School of Medicine, the study analyzed what exactly happens when pressure accumulates in the eye and causes damage to the nerve cells connecting the brain and eyes. For a long time, experts have associated this condition with glaucoma, but despite this, it was still unclear how cell death is caused by excess pressure.
The latest investigation showed that increased pressure caused astrocytes, which are star-shaped glial cells located in the central nervous system, to discharge neuron-killing toxins that are yet to be identified, probably to “clear away” the damaged cells.
In the meantime, excess pressure did not have a major impact on nerves in the absence of astrocytes. Moreover, when astrocytes were inhibited from responding to pressure, neurons were affected but not quite badly.
Our findings point to astrocytes as the true culprits behind nerve cell death and highlight a new way of treating a neurodegenerative disease like glaucoma. Perhaps targeting astrocytes after an injury may be the way to keep neurons healthy and help prevent further deterioration.”
Shane Liddelow, PhD, Study Senior Author and Assistant Professor, Department of Neuroscience and Physiology, NYU Langone Health
Liddelow, who is also an assistant professor in the Department of Ophthalmology at NYU Langone Health, added that while 50% of all brain cells are astrocytes, a majority of studies on glaucoma have historically targeted neurons—the electrically active cells that transmit messages all through the nerve tissues.
According to him, the study results show clearly that to interpret neurodegenerative disorders, experts should look beyond neurons to the cells surrounding them, such as astrocytes, dubbed after the Greek word for star.
Liddelow’s previous studies in rodents demonstrated that astrocytes may react instantly after the nerves are physically damaged. According to the study authors, the latest analysis, which would be published online in the Cell Reports journal on June 23rd, 2020, is believed to be the first to demonstrate that reactive astrocytes destroy cells over a period of time in a process analogous to what happens in glaucoma.
Additionally, the study findings may help describe why brain cells continue to die even after the prolonged control of excess pressure.
Liddelow believes that inflammatory compounds are spilled into the surrounding tissue by dying neurons and this may additionally aggravate the astrocytes and result in a continuous cycle of cell damage.
The study authors, for their investigation, increased eye pressure for a period of two weeks in several dozen mice and rats. The researchers genetically engineered a few of these animals such that they lack the neuron-killing reactive astrocytes.
They observed that the unmodified mice lost up to 50% of the neurons in the site of injury, while those without the toxic astrocytes experienced little cell death. Furthermore, neurons that survived continued to transmit electrical signals.
To test whether neurons can survive if astrocytes are inhibited from discharging toxins, the scientists increased the pressure again, but this time they disrupted inflammation in certain animals to inhibit their astrocytes from becoming reactive.
While these findings imply that the inhibition of astrocytes is a potential method for preventing nerve damage that occurs in glaucoma patients, Liddelow cautioned that scientists are yet to know whether the ensuing effects are permanent or what side effects are likely to occur.
The researchers are planning to examine if such a treatment can actually enhance vision in animals affected by glaucoma, and also to analyze the behavior of astrocytes in associated diseases, like Parkinson’s, Alzheimer’s, and Lou Gehrig’s disease.
Guttenplan, K. A., et al. (2020) Neurotoxic Reactive Astrocytes Drive Neuronal Death after Retinal Injury. Cell Reports. doi.org/10.1016/j.celrep.2020.107776.