Brain Cells Of ‘Villainous Character’ Might Explain Diseases Like Parkinson’s
There are 100 billion neuronsin the human brain and four times as many astrocytes, a type of star-shaped cell populating the central nervous system.
Healthy astrocytes are essential to brain health, promoting survival and growth of neurons, as well as maintaining the blood-brain barrier. But when they turn unhealthy, they kill neurons and synapses, potentially leading to neurodegenerative diseases.
Neurologists at Stanford University School of Medicine have found that normally beneficial astrocytes can break bad, taking on a villainous character and destroying nerve cells in mass quantities.
The findings,published last week in the journal Nature, showed that this process is a likely driver of conditions like Parkinsons, Huntingtons, multiple sclerosis and Alzheimers.
Lead researcher Dr. Ben Barres, who has been studying astrocytes for more than three decades, said the findings werethe most important discovery my lab has ever made.
Most medications for these diseases so far have targeted neurons, but the new findings suggest treatments could be aimed at astrocytes, too. Blocking these cells from turning toxic, or countering the toxins they secrete, could prevent the synaptic loss that leads to neurodegenerative diseases.
Weve learned astrocytes arent always the good guys, Barres, a neurobiologist at the university and the studys senior author, said in a university statement.
When an evil form of astrocytes begin popping up, they act like mass murderers, killing off large numbers of neurons and synapses. These murderous astrocytes are found in large quantities in brain tissue samples of patients with brain injuries, and those with neurological disorders like Alzheimers and multiple sclerosis.The implications for treating these diseases are profound, Barres said.
Scientists look elsewhere as bad astrocytes get away with murder.
Astrocytes were commonly dismissed as a benign sort of filler, but scientists now know that they provide important support and instructions for neurons. They can be beneficial. But they can also take on insidious forms.
Astrocytes are normally regarded as the good guys, but here we have convincing evidence of a well-defined mechanism for how they contribute to different types of pathologies,German molecular physiologist Dr. Frank Kirchoff, who was not involved in the study, told Scientific American.
Things like brain injury or infection have been known to transform resting astrocytes, which are benign, into potentially dangerous reactive astrocytes.
In a previous study, Barre identified two types of reactive astrocytes, one benign (A2) and the other harmful (A1). The harmful ones were found to produce large volumes of pro-inflammatory substances. Barres and his team were able to determine how A1 astrocytes are generated, and what they do to neurons.
How do good astrocytes turn bad?
The brains immune cells become activated when theyre exposed to a certain compound found in bacteria, and begin releasing pro-inflammatory substances that change the behavior of astrocytes.
In the new study, the scientists identified three pro-inflammatory substances. Alone, each had an effect of partially inducing A1s. When secreted together, they completely switched healthy, resting astrocytes which support the formulation and functioning of synapses into bad A1s, which are toxic to neurons.
For one experiment, the researchers compared rodents that had resting astrocytes in their brains with others that had reactive astrocytes. The rodents with the bad A1 astrocytes had onlyhalf as many synapses as the other rodents! Thats a big deal, as synapses are critical to learning and memory, and losing them is an early warning sign of Alzheimers.In another experiment, the researchers showed that A1s release a powerful neuron-killing toxin.
For their final experiment, the researchers analyzed brain tissue samples from patients with Alzheimers, Parkinsons, Huntingtons, ALS and MS. In each case, they observed big clusters of A1s located exactly where the disease was most active.
Revealing new possibilities for protecting brain health.
Taken together, the results of the experiments strongly suggest that these toxic cells are a key driver of neurodegeneration that occurs in these diseases and a potential doorway to more effective medications.
The strong implication is that A1s are driving neurodegeneration in all of these diseases, Barres told HuffPost. Blocking A1 formation or reverting A1s back to normal astrocytes, or by blocking the toxin or its receptor may prevent or delay neurodegeneration in all of these diseases, as well as preventing death of neurons after brain and spinal cord injury and after a stroke.
Barres added: The human brain, retina and spinal cord injuries may all be much more treatable than has been thought.
Much more research needs to be conducted before scientists can devise treatments, Barres noted. A next step is to identify the neurotoxin secreted by reactive astrocytes, and then to test the role of A1s in specific brain injuries and neurodegenerative diseases.