Brain cells more adaptable than thought: research
Imagine being able to flip a switch in your brain cells that would enable them to adapt and take measures to help with illnesses and conditions like epilepsy, Alzheimer’s disease, stroke and even brain injuries.
Groundbreaking research from the Research Institute of the McGill University Health Centre — which has shattered a long-standing assumption about brain cells known as astrocytes with a new study published on Thursday — has opened the door to the possibility of reprogramming those cells to preserve brain function.
It’s a long road until this new understanding of the brain could ever lead to treatments, but there is a lot of excitement these days in the lab of Keith Murai at the Montreal General Hospital, where post doctoral researcher Todd Farmer has been conducting his studies on mice.
“This changes some of the fundamental ways we believed the brain works,” Farmer, the study’s first author, said in an interview. “The results were surprising, which is why there is a lot of interest in this work.”
No one was more surprised than Farmer himself, in fact. Not only was it hard to convince others to accept his hypothesis, but Farmer remained skeptical and it took about two years of testing until he finally believed what he was seeing.
“Then it was really exciting,” he said.
The discovery, which shows that the brain has a far greater ability to adapt and respond to changes than previously believed, could have significant implications for epilepsy, movement disorders and psychiatric and neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease.
“Now we realize astrocytes change and can behave differently under certain conditions,” said Farmer. “So could we coax them to behave the way we want them to?”
It seems they can, but one of the next big questions his research will focus on will be the behaviour of astrocytes in relation to disease. Farmer acknowledged, however, that when there is a fundamental discovery such as this, it often raises more questions than it answers. This topic may very well be his life’s work now.
Published in the current issue of the journal Science, the study shows that astrocytes, which play fundamental roles in nearly all aspects of brain function, can be adjusted by neurons in response to injury and disease.
Previously, the long-held understanding was that the identity of cells is set during development and stays like that for life, Farmer said.
“But it turns out they are flexible and they could change their properties in drastic, drastic ways,” he said.
Murai — senior author on the study and director of the Centre for Research in Neuroscience at the RI-MUHC, as well as an associate professor in the department of neurology and neurosurgery at McGill — said the newly discovered flexibility means the cells are “potentially modifiable, which enables them to improve brain function or restore lost potential caused by disease.”
The researchers studied a specific pathway called the Sonic Hedgehog signalling pathway. Using advanced genetics and microscopy techniques, they found the SHH pathway could induce disparate changes in astrocytes in different brain regions.
They found a figurative dial on the astrocytes that can be used to tune its response in the normal brain — but also in different diseases like Alzheimer’s or Parkinson’s, or injuries such as stroke and trauma.
“Our findings help us to better understand the complexity of the brain and also grasp mechanisms that can be used to reduce brain injury and disease,” Farmer said. Although they were dealing with mature healthy brains, the responses they saw were changes in the amounts of proteins that have well documented involvement in human disease.
Inez Jabalpurwala, president and CEO of the Brain Canada Foundation (which helped fund the study along with the Canadian Institutes of Health Research and the Weston Brain Institute), said in a statement that the study was a “remarkable discovery that will advance our understanding of fundamental mechanisms that play a role in brain disease. We are pleased to support this kind of transformative research, which will ultimately lead to improved health outcomes.”
Having identified this novel mechanism, Murai said the goal now is to see how it is affected in different brain diseases and determine if it can be harnessed to protect neurons and, ultimately, preserve brain function.