Researchers find that the immune cells of the brain, microglia, play a crucial role in brain development during adolescence, but that its role is different in males and females. The study, published yesterday in Nature Communications, may improve understanding of the neurologic basis of both normal behavioral changes in adolescence, such as increased experimentation and risk-taking, and of neuropsychiatric disorders that typically emerge during adolescence.
"We found that microglia and other immune system proteins eliminate dopamine receptors in a reward-associated part of the brain called the nucleus accumbens in adolescent male rats, and this process shapes normal changes in social behavior that occur during adolescence," says Staci Bilbo, Ph.D., of Massachusetts General Hospital. "Although this specific process occurs in males only, dopamine receptors also change over adolescence in females as well; we just don't yet know the mechanism by which that occurs."
Microglia are known to participate in the early development of the brain by removing unneeded synapses—points of communication between brain cells—in key regions. Bilbo's team set out to investigate whether microglia also contribute to development during adolescence, a time when the brain's reward circuitry, the dopamine system, undergoes significant changes.
Because previous observations suggest that the D1 dopamine receptors in the nucleus accumbens play a critical role in social behavior, the team examined the levels of D1 receptors and of an immune protein that tags molecules for removal by microglia in both male and female rats at different stages of development. They found that, while D1 receptor levels in the nucleus accumbens drop in early adolescence (20–30 days) in females and mid-adolescence (30–38 days) in males, microglia-based immune signaling was involved in that reduction only in males. They also found that the microglia-based reduction of D1 receptors in males is required for normal adolescent behavioral changes, specifically a reduction in “rough and tumble” play behavior, between early and late adolescence. In females, while altering microglia-based immune signaling also influenced social play, the changes were subtler and did not rely on D1 receptor reduction.
Bilbo notes that their findings raise several questions for future research, including whether aberrations in neuroimmune development could contribute to neuropsychiatric disorders that typically emerge in sex-specific patterns during or soon after adolescence, such as depression in females and schizophrenia in males.