Researchers have established that biological sex plays a role in determining an individual’s risk for brain disorders. For example, boys are more likely to be diagnosed with behavioral disorders such as autism or attention deficit disorder, while women are more likely to suffer from anxiety disorders, depression, or migraines. However, experts do not fully understand how sex contributes to brain development, particularly in the context of these diseases. They think, in part, that it may have something to do with the different sizes of certain brain regions.
Researchers at the University of Maryland School of Medicine now believe they have identified the mechanism for why and how a region of the brain differs in size between men and women, according to a February study published in PNAS. The study in rats found that immune system cells in the female brain consume and digest neurons to sculpt this region of the brain during development.
The researchers also found that tinkering with the size of this brain region, which forms in the first few days of life, affected whether female rats still preferred the scent of male rats. In rodents, this “odor preference” is an indicator of sexual partner preference, and female rats often prefer male odors. Although these rat inclinations don’t apply directly to human sexual partner preferences, the findings show that changes in the brain that are determined by the immune system can affect behavior later on.
Understanding in detail how biological sex and the immune system help shape the developing brain may one day help experts understand why certain brain diseases are more likely to occur in one sex than another and could shed light on better ways. to treat or prevent these conditions.
“Although there is a lot of overlap between the brains of men and women, it appears to be the immune system that provides much of the natural variation. This may occur because the immune system is designed for variability so that it can respond to a wide range of attacks from the outside world,” said UMSOM dean Mark Gladwin, MD, vice president of medical affairs at the University of Maryland, Baltimore, and John Z. and Akiko K. Bowers Distinguished Professor.
For the current study, Dr. McCarthy and her colleagues examined a region located deep in the brain that is two to four times larger in male rats than in female rats. This size difference also appears in the brains of people in a similar region, but the sex difference is not as pronounced.
When they closely examined different types of cells in the male and female brain, they noticed that the immune cells in the female rats’ brains had formed more structures on their surface that immune cells use to eat other cells, called phagocytic cups. They also observed that these immune cells digest neurons. Typically, these immune cells eat debris, dead or dying cells, and cells infected with viruses or bacteria, instead of healthy brain cells.
When the researchers used a drug or antibody to block the ability of immune cells to eat neurons in rat brains, they found that this region in the female rat brain grew larger, similar to the size of the region in the brain of rats. male rat.
“For nearly 50 years, we had thought that cells simply died in females and not in males, and we thought this was due to steroid hormones,” said lead investigator Margaret McCarthy, PhD, professor and chair of the James and Carolyn Frenkil Dean’s Department of Pharmacology of the UMSOM. “In an open field of cells touching each other, we will see a microglia immune cell shoot through other cells and eat a particular cell. The cells that eat these microglia are not random, but we don’t know why they are chosen. These are the kinds of questions we still need to investigate.”
The region of the brain analyzed in this study is known to control the reproductive behaviors of rats. For example, female rats often prefer the odors of male rats when given a choice, and male rats prefer the odors of females. The researchers found that females with the largest brain region because the feeding function of their immune cells was blocked no longer preferred the scent of the male rat and instead chose the female scent or had no preference at all.
“This finding adds to the evidence that the immune system plays an important role in determining certain sex differences in the brain that may ultimately lead to differences in the prevalence of brain development disorders,” said Dr. Dr. McCarthy. “Whether this process can be manipulated to develop new treatments for autism or anxiety remains to be seen, but it is a promising avenue of research to explore.”
Dr. McCarthy is also the director of the newly created University of Maryland Medicine Institute for Neuroscience Discovery (UM-MIND), which was founded to bring together basic and clinical scientists to facilitate the translation of discoveries about the brain. in new treatments for diseases of the brain. His area of expertise lies between the institutional strengths of neurodevelopmental and psychiatric disorders. The other focuses of the institute are neurotrauma and brain injury, as well as aging and neurodegeneration.
The National Institute of Neurological Disorders and Stroke (F31NS093947) of the National Institutes of Health, the National Institute of Mental Health (F31MH123025 and R01MH52716), and the National Institute on Drug Abuse (R01DA039062).
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