Mini Brains Maximize Insight into Parkinson’s Disease

Nguyen-Vi Mohamed
Post-Doctoral Researcher
McGill University

McGill University postdoctoral researcher Nguyen-Vi Mohamed has developed techniques for transforming human stems cells into neurons and then arranging them in a 3D pattern resembling the midbrain. The resulting “mini brains” have become her model system for exploring the behaviour of a key protein in the development of Parkinson’s disease, which could in turn point the way to mechanisms that could halt or even reverse this process.

In order to analyze specific biochemical features of the brain, McGill University postdoctoral researcher Nguyen-Vi Mohamed employs a model made out of brain cells she has grown in her laboratory. These “mini brains” as she calls them, replicate the structure of the human midbrain and display the intricate functions responsible for how this mysterious organ works—or, in the case of a neurodegenerative disease like Parkinson’s – slowly stops working.

Mohamed’s research is made possible through a Basic Research Fellowship from the   Parkinson Canada Research Program, and funded in partnership with Fonds de recherche du Québec – Santé (FRQS) for $50,000 over two years.

“In order to grow them, the idea is to mimic what is happening during the developmental process,” says Mohamed, who has moved far beyond a simple flat array of cells in a dish. “This is a complex 3D model with different types of cell populations. In 3D the cells have more mature functionalities, thanks to the diversity of cell populations.”

Her work focuses on alpha-synuclein, a protein that is intimately associated with the onset of Parkinson’s. Previously, Mohamed had been studying how this agent builds up in the brains of mice, but she concluded the results were not necessarily applicable to what is happening in the human body. Mohamed turned to stem cells induced from the blood of human volunteers, from which she then takes the cells she uses to assemble mini brains.

“The idea is to work with the genetic background of the patient,” she says. “This makes the pathology of the disease more personalized.”

Mohamed acknowledges that this approach, like the entire field of stem cells, is relatively new. It depends on a deft combination of biochemical signaling and special storage vessels to put these undifferentiated cells in the right proximity to one another so that they first become neurons, then arrange them in patterns reflecting what might be found in a living brain.

She insists that the effort is well worthwhile, as the mini-brains are already shedding light on the way alpha-synuclein uses brain cells to propagate, which is the first step toward understanding how Parkinson’s maintains its neurodegenerative pace.

“These new insights should have a direct impact on the development of new drugs to block the progression of the disease,” she says.

“The idea is to study the propagation of alpha-synuclein in a personalized and complex brain model.”

Read about other researchers recently funded by the Parkinson Canada Research Program by visiting the research section of www.parkinson.ca.

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