Brown Lab discovers that microglia migration is dependent on sex and interferon signalling

In their new paper published in the Proceedings of the National Academy of Science, Dr. Craig Brown and his team—former post-doctoral fellow and first author Roobina Boghozian, post-doctoral fellow Sorabh Sharma, master’s student Kamal Narayan, and research assistant Manjinder Cheema—show that microglia migration in the mature brain is dependent on sex and interferon signalling.

“The idea that some cells can roam around our brain throughout life is really fascinating to me” says Dr. Brown. “This is why our lab spent two years trying out different methodological approaches to studying these movements. I think there is a whole new frontier of questions that people will have about this roaming behaviour.”

Microglia are innate immune cells that possess the unique ability to migrate in the mature brain. Although this ability has been recognized by past literature, single cell tracking of their movements has been limited. For this paper, first author and former Brown Lab post-doctoral fellow Roobina Boghozian was able to sparsely label a few microglia with a fluorescent marker, which she tracked and imaged in the living brain. This allowed her to examine several open questions in the field, such as: Are all microglia equally capable of migrating? How far can these cells travel in a day? What molecular or biological factors such as sex, regulate this mobility?

After four years of study, Roobina discovered that only a small fraction of microglia (about five per cent) move around in the healthy brain. However, when injury occurs, about 25 per cent of these cells migrate towards the injury where they presumably play a role in repair.

Unexpectedly, microglia in male brains were more likely to migrate, and they migrated greater distances towards the site of injury compared to their female counterparts. Furthermore, manipulating an inflammatory cytokine called interferon gamma had much stronger impact on microglia movements in males than in females.

“Perhaps we were being naïve, but these striking sex differences surprised us. It really reinforces the idea that males and females can have quite different immunological responses to brain injury. Now we have a bunch of new questions to address regarding why these sex differences exist and what are the functional consequences of these differences in migration,” says Dr. Brown.