Imagine being able to flip a switch in your brain cells that wouldenable them to adapt and take measures to help with illnesses andconditions like epilepsy, Alzheimer’s disease, stroke and even braininjuries.
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 newstudy published on Thursday — has opened the door to the possibility of reprogramming thosecells to preserve brain function.
It’s a long road until this new understanding of the brain could ever lead to treatments, but there isa lot of excitement these days in the lab of Keith Murai at the Montreal General Hospital, where postdoctoral 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’sfirst author, said in an interview. “The results were surprising, which is why there is a lot of interestin this work.”
No one was more surprised than Farmer himself, in fact. Not only was it hard to convince others toaccept his hypothesis, but Farmer remained skeptical and it took about two years of testing until hefinally 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 changesthan previously believed, could have significant implications for epilepsy, movement disorders andpsychiatric and neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease.
“Now we realize astrocytes change and can behave differently under certain conditions,” saidFarmer. “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 behaviourof astrocytes in relation to disease. Farmer acknowledged, however, that when there is afundamental discovery such as this, it often raises more questions than it answers. This topic mayvery well be his life’s work now.
Published in the current issue of the journal Science, the study shows that astrocytes, which playfundamental roles in nearly all aspects of brain function, can be adjusted by neurons in response toinjury and disease.
Previously, the long-held understanding was that the identity of cells is set during development andstays 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 theRI-MUHC, as well as an associate professor in the department of neurology and neurosurgery atMcGill — said the newly discovered flexibility means the cells are “potentially modifiable, whichenables them to improve brain function or restore lost potential caused by disease.”
The researchers studied a specific pathway called the Sonic Hedgehog signalling pathway. Usingadvanced genetics and microscopy techniques, they found the SHH pathway could inducedisparate 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 normalbrain — but also in different diseases like Alzheimer’s or Parkinson’s, or injuries such as stroke andtrauma.
“Our findings help us to better understand the complexity of the brain and also grasp mechanismsthat can be used to reduce brain injury and disease,” Farmer said. Although they were dealing withmature healthy brains, the responses they saw were changes in the amounts of proteins that havewell documented involvement in human disease.
Inez Jabalpurwala, president and CEO of the Brain Canada Foundation (which helped fund thestudy along with the Canadian Institutes of Health Research and the Weston Brain Institute), said ina statement that the study was a “remarkable discovery that will advance our understanding offundamental mechanisms that play a role in brain disease. We are pleased to support this kind oftransformative 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 indifferent brain diseases and determine if it can be harnessed to protect neurons and, ultimately,preserve brain function.
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