‘Thrill-seeking’ microglia reveal sex-specific differences in mice

Written by Sharon Salt, Editor

Credit: Meron Maricos, MDC

In a recent study published in Cell Reports, researchers from the Max Delbrück Center for Molecular Medicine (MDC; Berlin, Germany) have reported sex-specific differences in microglia in mice. They believe that these findings could potentially change how we treat neurological diseases.
Using brain slices and isolated cells, Susanne Wolf (MDC) and colleagues conducted a study on the structure and function of microglia. Their findings revealed that the brains of male mice contain more microglia, and that the cell bodies of brain immune cells in males were larger than their female counterparts.

In addition to this, the scientists also determined not only which genes were active in female and male cells but also what proteins were produced by these genes. The investigators identified over 1000 genes and 300–400 proteins that are regulated differently according to sex – with many of these being more active in male microglia.

“The microglia of male animals seem to be permanently at attention, ready to strike and keep order,” commented Wolf. She explained that their tests demonstrated higher voltage levels in the membranes of male cells even when they are idle. Additionally, according to Wolf, the cell surface contains more of those proteins responsible for stimulating T cells during inflammation.

In a separate experiment, the researchers treated microglia with ATP and discovered that male cells respond much more robustly to ATP than females.

According to Wolf, male microglia 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,” she stated. “In the male cells, on the other hand, we see increased activity of genes involved in initiating programmed cell death.” This could mean that male microglia may be less protected against environmental insults and quicker to activate the cellular suicide program.

Dilansu Guneykaya (MDC), first author of the study, said: “It almost seems as if the male cells are more willing to take risks than the female ones. They almost always react faster, but as a result they sometimes seem to put themselves in danger.”

Guneykaya has reported that as early as 2010, male animals are used in neuroscience studies much more than female animals – pointing out that this practice could distort findings. She cautions that researchers conducting patient studies to test medications for neurological disorders must be aware of the fact the brains of men and women could respond very differently to the same agent.

For example, autism is about four-times more prevalent among boys than girls. In contrast, 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,” concluded Wolf.

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Source: Max Delbrück Center for Molecular Medicine. The brain’s tiny thrill-seekers. Press release: www.mdc-berlin.de/news/press/brains-tiny-thrill-seekers