A mechanism for how androgens sculpt brain development has been discovered by University of Maryland School of Medicine researchers. The findings could ultimately help researchers understand behavioral development differences between males and females.

“We already knew that the brains of males and females are different and that testosterone produced during the second trimester in humans and late gestation in rodents contributes to the differences but we did not know how testosterone has these effects,"

said Margaret M. McCarthy, Ph.D., who Chairs the Department of Pharmacology.

Behavioral Differences

A key contributor to the differences in play behavior between males and females is a sex-based difference in the number of newborn cells in the part of the brain called the amygdala, which controls emotions and social behaviors. The research showed that males have fewer of these newborn cells, because they are actively eliminated by immune cells.

The research discovered a way in which androgens sculpt the brains of male rats to produce behavioral differences, such as more aggression and rougher play behavior.

In females, the newborn cells differentiated into a type of glial cell, the most abundant type of cell in the central nervous system. In males however, testosterone increased signaling at receptors in the brain which bind endocannabinoids, causing immune cells to be activated. The endocannabinoids prompted the immune cells to effectively eliminate the newborn cells in males.

Endocannabinoids Increased

Females rats in the study were unaffected, suggesting that the activation of the immune cells by the increased endocannabinoids in males was necessary for cell elimination. In this respect, this research shows that cannabis use, which stimulates endocannabinoids in the brain and nervous system, could impact brain development of the fetus and this impact could differ between male and female fetuses.

The results suggest that differences in androgen and endocannabinoid signaling may contribute to individual differences in brain development and thus behavioral differences among people.

“These discoveries into brain development are critical as we work to tackle brain disorders as early in life as possible, even in pregnancy,"

said UMSOM Dean E. Albert Reece, MD, Ph.D., MBA.

Jonathan W. VanRyzin, Ashley E. Marquardt, Kathryn J. Argue, Haley A. Vecchiarelli, Sydney E. Ashton, Sheryl E. Arambula, Matthew N. Hill Microglial Phagocytosis of Newborn Cells Is Induced by Endocannabinoids and Sculpts Sex Differences in Juvenile Rat Social Play Neuron (2019). DOI: 10.1016/j.neuron.2019.02.006

Image: University of Copenhagen

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