The brain's tiny thrill-seekers

September 4, 2018, Max Delbrück Center for Molecular Medicine
Microglia (pink) are a sort of garbage disposal for the brain. They quickly engulf small protein-coated latex balls and digest them Credit: Susanne Wolf, MDC

Microglia, the immune cells of the central nervous system, differ in male and female mice. MDC researchers have reported on the sex-specific features in Cell Reports. Their findings could change how we treat neurological diseases.

Microglia monitor the brain's health around the clock, much like a battalion of tiny soldiers. When the sense pathogens or an injury through their movable projections, they rush to the trouble spot—and try to save that which is still salvageable.

But they do so quite differently depending on the animal's sex. "We were really surprised to find so many differences between the microglia of male and female mice," says Dr. Susanne Wolf, senior author of the study published in the journal Cell Reports, and researcher in the Cellular Neurosciences Lab at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin.

Male cells are always ready for action

Together with colleagues at Charité - Universitätsmedizin Berlin and a group of researchers from Warsaw, Wolf conducted a study on the structure and function of microglia, using brain slices and isolated cells. "It turns out that the brains of male mice have more microglia," says Wolf. And, according to the researcher, that's not the only difference: the cell bodies of male brain immune cells are larger than their female counterparts.

She and her team also determined not only which genes are active in the male and , but also which proteins are produced by these genes. "We identified more than 1,000 genes and 300 to 400 proteins that are regulated differently according to sex," says Wolf. Many of them, she adds, are more active in male microglia—such as those that are involved in the production of defense molecules.

What's more, everything suggests that the male cells also act differently than female cells. "The microglia of male animals seem to be permanently at attention, ready to strike and keep order," Wolf says, adding that tests show there are higher voltage levels in the membranes of male cells even when they are idle. And, according to the researcher, the cell surface contains more of those proteins responsible for stimulating T cells during inflammation.

In another experiment, the team of researchers treated microglia with the signaling molecule ATP, which is released in greater amounts when the brain suffers an injury. "We discovered that male cells respond much more robustly to ATP than their female counterparts—a response that includes higher ion currents and increased production of certain proteins, among other things," explains Wolf.

Female microglia have better survival skills

Male microglia, says the researcher, appear to wear themselves out faster because of their constant alertness. "In the female cells, proteins and genes responsible for protecting cells, such as DNA repair genes, are more active," Wolf explains. "In the male cells, on the other hand, we see increased activity of genes involved in initiating programmed cell death." This means, she adds, that male microglia might be less protected against environmental insults and quicker to activate the cellular suicide program.

"It almost seems as if the male cells are more willing to take risks than the female ones," says the study's first author Dilansu Guneykaya, a Ph.D. student at the MDC. "They almost always react faster, but as a result they sometimes seem to put themselves in danger."

Another study recently published in Cell Reports also confirms that the thrill-seeking nature of male microglia does not always pay off. "The Italian researchers were able to show that the cells of male mice had a harder time dealing with an experimentally induced stroke than the of ," reports Wolf. "But when female microglial cells were implanted in the brains of male mice, the effects of vascular obstruction were less severe in these rodents."

Therapies need to take greater account of differences

As early as 2010, reports Guneykaya, researchers criticized in the journal Nature that male animals are used in neuroscience studies much more than female animals—pointing out that this practice could distort findings. "Our study clearly confirms this hunch: the brain immune cells of both sexes act very differently," says Guneykaya. It is crucial, she adds, that this insight be taken into account in future research on neurological, and especially, psychiatric disorders.

"At the University of Groningen, with whom we collaborate closely, there are plans to repeat our murine experiments with human material taken from recently deceased donors," reports Wolf. But, she adds, already today researchers conducting patient studies to test medications for neurological disorders must be aware of the fact the brains of men and woman could respond very differently to the same agent.

"Sex-specific differences can also be seen in the frequency of neurological disorders," add Wolf. Autism, for example, is about four times more prevalent among boys than girls. In contrast, about twice as many women than men suffer from multiple sclerosis. "The differences are there, but are not yet sufficiently taken into account when treating patients," says Wolf. She adds that she hopes her study will help change this.

Explore further: Immune cells in the brain have surprising influence on sexual behavior

More information: Cell Reports (2018). DOI: 10.1016/j.celrep.2018.08.00

Related Stories

Immune cells in the brain have surprising influence on sexual behavior

August 14, 2018
Researchers have found a surprising new explanation of how young brains are shaped for sexual behavior later in life.

Female mice are immune to cognitive damage from space radiation

August 20, 2018
Humankind still dreams of breaking from the bounds of Earth's atmosphere and venturing to the moon, Mars and beyond. But once astronauts blast past the International Space Station, they become exposed to one of the many dangers ...

Researchers identify brain cells responsible for removing damaged neurons after injury

June 25, 2018
Researchers at the University of Virginia School of Medicine have discovered that microglia, specialized immune cells in the brain, play a key role in clearing dead material after brain injury. The study, which will be published ...

Why male and female cells behave differently after being reprogrammed into stem cells

April 19, 2018
Vincent Pasque from KU Leuven, Belgium, and Kathrin Plath from UCLA led an international study into how specialized cells are reprogrammed to induced pluripotent stem cells (iPS). The researchers discovered that female and ...

The effect of gut microbes on the mouse brain depends on both sex and stage of development

May 2, 2018
Immune cells in a mouse's brain react differently to changes in gut-dwelling bacteria depending on whether the mouse is male or female and whether it is a fetus or an adult, A*STAR researchers have found. This discovery has ...

Microglia are key defenders against prion diseases

May 17, 2018
Prion diseases are slow degenerative brain diseases that occur in people and various other mammals. No vaccines or treatments are available, and these diseases are almost always fatal. Scientists have found little evidence ...

Recommended for you

Cell study reveals how head injuries lead to serious brain diseases

November 16, 2018
UCLA biologists have discovered how head injuries adversely affect individual cells and genes that can lead to serious brain disorders. The life scientists provide the first cell "atlas" of the hippocampus—the part of the ...

Newborn babies' brain responses to being touched on the face measured for the first time

November 16, 2018
A newborn baby's brain responds to being touched on the face, according to new research co-led by UCL.

Playing high school football changes the teenage brain

November 16, 2018
A single season of high school football may be enough to cause microscopic changes in the structure of the brain, according to a new study by researchers at the University of California, Berkeley, Duke University and the ...

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

New brain imaging research shows that when we expect something to hurt it does, even if the stimulus isn't so painful

November 14, 2018
Expect a shot to hurt and it probably will, even if the needle poke isn't really so painful. Brace for a second shot and you'll likely flinch again, even though—second time around—you should know better.

A 15-minute scan could help diagnose brain damage in newborns

November 14, 2018
A 15-minute scan could help diagnose brain damage in babies up to two years earlier than current methods.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.