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UCI develops humanized mice to study human brain cells’ role in Alzheimer’s disease

UC Irvine
Scientists at UC Irvine, pictured, developed a way for human brain immune cells to grow and function in the rodents — a breakthrough that could give an “unprecedented view of crucial mechanisms” contributing to Alzheimer’s and other brain diseases long before symptoms emerge, the university says.
(File Photo / Los Angeles Times)

Researchers studying brain illnesses have a powerful new tool to study Alzheimer’s disease — humanized mice.

Scientists at UC Irvine developed a way for human brain immune cells to grow and function in the rodents — a breakthrough that could give an “unprecedented view of crucial mechanisms” contributing to Alzheimer’s and other diseases affecting the brain long before symptoms emerge, UCI said in a statement.

Microglia, a type of cell found in the brain, “are now seen as having a crucial role in the development and progression of Alzheimer’s,” said Mathew Blurton-Jones, a UC I associate professor of neurobiology and behavior who directed the study. “The functions of our cells are influenced by which genes are turned on or off. Recent research has identified over 40 different genes with links to Alzheimer’s, and the majority of these are switched on in microglia. However, so far we’ve only been able to study human microglia at the end stage of Alzheimer’s in post-mortem tissues or in petri dishes.”

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University researchers created the new specialized mouse model, called “chimeric,” for its ability to grow human brain cells in a specimen that can be studied while the cells mature.

To achieve that, which took four years, researchers used a type of stem cell called induced pluripotent stem cells, or iPSCs, that can be donated by human adult patients.

“The question was, can you get these stem cells to mature into microglia?” Blurton-Jones said. “A few years ago, we figured out how to do that.”

The researchers coaxed the iPSCs into becoming young microglia and implanted them into young genetically modified mice, according to UCI.

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“The type of stem cells we are using don’t have much of an ethical debate,” Blurton-Jones said. They are made from cells that people can donate, like skin cells.

Microglia are the central nervous system’s primary immune cells and respond to pathogens by producing inflammation. When an infection or injury occurs, they respond to the area of illness rapidly to direct the immune response. They also play a role in the anti-inflammatory response.

But while microglia play a protective role in the brain, they also play a harmful role in neurodegenerative diseases such as Alzheimer’s and Parkinson’s and traumatic brain injuries and strokes — a dichotomy that is not yet clearly understood, underscoring the need to better comprehend the cells’ behavior and how they mature, UCI said.

“In addition to yielding vital information about Alzheimer’s, this new chimeric rodent model can show us the role of these important immune cells in brain development and a wide range of neurological disorders,” study co-author Morgan Coburn, a graduate student in neurobiology and behavior, said in a statement.

The details of the study are published in the journal Neuron.

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