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New hope for treating “chemo brain,” with a side of the joy of science

Wu Tsai Neurosciences Institute, Michelle Monje
Photo by Erin Digitale

Bu Erin Digitale

A few years ago, one of my coworkers caused a minor fracas by showing up at our annual holiday party with buttons that said “Ask me about microglia.” Everyone wanted one; our crew of science communicators is very nerdy.

Microglia belong to a group of brain cells — glia — whose secrets were unlocked by the late Stanford neuroscientist Ben Barres, MD, PhD. Our team’s enthusiasm for these cells was stoked by one of my fellow writers, who would periodically come to meetings bubbling with excitement about new research from the Barres lab. It made me wish I was writing about these cool cells.

Then a neuroscientist on my beat asked me to cover her team's newest discovery: Microglia play a key role in "chemo brain," a problem affecting millions of cancer survivors. Known more formally as cognitive impairment following cancer treatment, chemo brain is especially severe for children.

In the new paper, published in CellMichelle Monje, MD, PhD, and her colleagues showed that microglia are conducting a symphony of problems in chemo brain. Chemotherapy over-activates the microglia, triggering malfunctions in two other types of glia.

From our press release:

'The biology of this disease really underscores how important intercellular crosstalk is,' Monje said. 'Every major neural cell type is affected in this pathophysiology.' She suspects this type of complex dysfunction may also underlie other cognitive disorders. 'I think that is probably more the rule than the exception,' she said.

Importantly, Monje’s team also showed that when you administer a different drug that depletes microglia to mice with chemo brain, the cognitive symptoms resolve. It’s an encouraging step toward targeted therapies for people experiencing chemo brain, she told me.

While I had Monje on the phone, I jokingly told her the story of my “Ask me about microglia” button. She laughed but then grew serious, noting that Barres, who died last winter, is a co-author on the new paper.

“Ben was a mentor of mine for 20 years,” she said. During her final visit to him, though quite weakened by cancer, he wanted updates on their data. She filled him in. “His eyes just shot open; he was so focused and present and asked three really good questions,” Monje said. “And when someone else came, his next visitor, he said ‘Go away, we’re talking about glia.’”

She laughed again. “I wish I could dedicate the paper to Ben,” she added. “This was our last collaboration, and in a very nerdy way, it is so gratifying that all major classes of glia ended up being important for this project.”