To develop male behavior, rats need immune cells

Research reveals unexpected role for cells called microglia in shaping the brain

Immune cells that help heal injuries in the adult brain may have a second job early in life, a study in rats reveals. The brain crusaders unexpectedly moonlight as sculptors, shaping a region of the brain into a male-specific form.

The cells, called microglia, are mobile garbage disposals that travel around the brain and gobble up damaged cells and infectious agents. But the new study, published in the Feb. 13 Journal of Neuroscience, emphasizes that these cells have diverse functions, says neuroscientist Jean Harry of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., who was not involved in the work.

Earlier results hinted that parts of the immune system have a role in building sex differences into the brain, so Kathryn Lenz and her colleagues at the University of Maryland, Baltimore decided to test whether microglia are pulling double duty. 

The team focused on the preoptic area of the rat brain—“a place where you see a ton of sex differences,” Lenz says. Early in life, this brain area gets shaped by sex hormones including molecules called estradiol and prostaglandin E2, which work on the male rat brain. In males, the preoptic area is larger, and the cells there have more elaborate shapes than in females. Scientists think those brain differences drive mating behaviors.

Lenz and her colleagues found another difference in the preoptic area between males and females: Young males had about twice as many active microglia as females did. What’s more, a dose of estradiol or prostaglandin E2 in the first few days of life caused female animals to produce the male number of active microglia.

This difference in number of microglia is important for behavior, the team found. After they matured, the females with the male number of microglia behaved more like male rats, mounting other females, for instance. When researchers gave these rats a drug to deactivate these microglia, the male behavior lessened. (The researchers focused on females because so much of the rat brain takes a male form prenatally that it’s hard to prevent a male brain from developing as male.)

Microglia might act as amplifiers of hormones in the male brain, Lenz says. These cells can both sense prostaglandin E2 and produce it—processes that could set up the conditions for the male brain to develop.

Harry cautions that it’s too soon to conclude that microglia cause these changes in behavior. “It’s the chicken and the egg with these cells,” she says. Microglia are notoriously reactive to their environment, she says, so it’s hard to know whether the cells are driving the change, or responding to other changes themselves.

It’s also unclear whether a similar process happens in humans, Lenz says, though scientists have seen hints that microglia are involved in psychiatric disorders such as autism, which affects males more than females.

Note: This story was corrected on February 13, 2013, to reflect that the study was performed with rats, not mice.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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