The researchers’ results hinged on an unconventional experiment: transplanting different kinds of microglia brain cells into mice that lack microglia altogether.
The researchers found that non-Hoxb8 microglia act as a gas pedal for anxiety. When researchers transplanted non-Hoxb8 microglia into mice without any other microglia, the mice groomed themselves compulsively and spent less time in open spaces—classic signs of higher anxiety. With only non-Hoxb8 microglia, the accelerator for anxiety was always on, with no brake pedal to keep it in check.
The other kind of microglia, Hoxb8 microglia, act as the brake pedal for anxiety. Mice transplanted with only Hoxb8 microglia weren’t anxious. And, importantly, mice with both kinds of microglia—the gas and the brake—weren’t anxious either. Non-Hoxb8 microglia might be driving the mice towards anxiety, but it was balanced out by the anxiety-preventing activity of Hoxb8 microglia, so the mice did not show anxiety behaviors.
“These two populations of microglia have opposite roles,” explains Mario Capecchi, PhD, distinguished professor of human genetics at University of Utah Health and the senior author on the study. “Together, they set just the right levels of anxiety in response to what is happening in the mouse’s environment.”