Shaping Minds: How the Immune System Shapes the Developing Rat Brain

Summary: Immune system cells in the brains of female rats consume and digest neurons, sculpting a specific brain region during development and potentially impacting behavior.

This insight into the interplay between biological sex, the immune system, and brain development may pave the way to understanding the increased prevalence of certain brain disorders in one sex and could inform future treatments or prevention strategies.

Key points:

  1. Immune system cells in the brains of female rats consume and digest neurons, shaping a specific region of the brain during development.
  2. This process could impact behavior, such as olfactory preference, which is an indicator of mate preference in rodents.
  3. Understanding the role of biological sex and the immune system in brain development can help explain the prevalence of certain brain disorders in one sex over another.

Source: University of Maryland

Researchers have established that biological sex plays a role in determining an individual’s risk of brain disorders. For example, boys are more likely to be diagnosed with behavioral disorders like 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, especially 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.

According to a February study published in PNAS.

The rat study found that immune system cells in female brains 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 during the first two days of life, affected whether female rats still preferred the smell of male rats. In rodents, this “olfactory preference” is an indicator of mate preference, with female rats generally preferring male odors.

Although these rat inclinations do not directly apply to human sexual partner preferences, the results demonstrate that brain changes determined by the immune system can subsequently affect behavior.

Understanding in detail how biological sex and the immune system help shape brain development could one day help experts understand why certain brain diseases are more likely to occur in one sex over another and could shed light on better ways to treat or prevent these conditions.

“Although there is a lot of overlap between male and female brains, it seems to be the immune system that provides much of the natural variation. This can happen because the immune system is designed for variability so 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 Professor Emeritus John Z. and Akiko K. Bowers.

For the current study, Dr. McCarthy and his colleagues looked at a region deep inside the brain that in male rats is two to four times larger than in female rats. This size difference also appears in the brains of people from a similar region, but the gender difference is not as pronounced.

When they looked closely at different types of cells in the brains of males and females, they noticed that the immune cells in the brains of female rats had formed more structures on their surface that immune cells use to eat other cells, called phagocytic cups.

They also observed these immune cells digest the neurons. Typically, these immune cells eat debris, dead or dying cells, and cells infected with viruses or bacteria, rather than healthy brain cells.

When researchers used a drug or antibody to block the ability of immune cells to eat neurons in rat brains, they found that this region of female rats’ brains grew larger, similar to the size of the region. brains of male rats.

“For nearly 50 years we thought cells were dying in women and not men and we thought it was due to steroid hormones,” said lead researcher Margaret McCarthy, PhD, Dean James and Carolyn Frenkil Professor and Chair of the Department of Pharmacology at UMSOM.

“In an open field of cells all touching each other, we will see a microglia immune cell walk through the other cells and eat a particular cell. The cells that these microglia eat 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 reproductive behaviors in rats. For example, female rats generally prefer odors from male rats when given the choice, and male rats prefer odors from females.

This shows a slice of brain
The rat study found that immune system cells in female brains consume and digest neurons to sculpt this region of the brain during development. Credit: The Researchers

Researchers found that females with the largest brain region due to their immune cells having their food function blocked no longer preferred the male rat odor and instead chose the female rat odor or had no preference.

“This finding adds to the evidence that the immune system plays a major role in determining certain sex differences in the brain that may ultimately lead to differences in the prevalence of brain developmental disorders,” said Dr. McCarthy.

“It remains to be seen whether this process can be manipulated to develop new treatments for autism or anxiety, but it is a promising avenue of research to explore.”

Dr. McCarthy is also director of the new University of Maryland-Medicine Institute for Neuroscience Discovery (UM-MIND), which was founded to bring together basic and clinical scientists to better facilitate the translation of brain discoveries into new treatments for patients. brain diseases.

His area of ​​expertise falls within the institutional strengths of neurodevelopment and psychiatric disorders. Other areas of interest of the institute are neurotrauma and brain injury, as well as aging and neurodegeneration.

Funding: National Institutes of Health’s National Institute of Neurological Disorders and Stroke (F31NS093947), National Institute of Mental Health (F31MH123025 and R01MH52716) and National Institute on Drug Abuse (R01DA039062).

About this neurodevelopment research news

Author: Vanessa McMains
Source: University of Maryland
Contact: Vanessa McMains – University of Maryland
Picture: The image is attributed to the researchers

Original research: Access closed.
“Phagocytosis of microglia mediates the volume and function of the sexually dimorphic rat nucleus of the preoptic area” by Mark Gladwin et al. PNAS


Microglia phagocytosis mediates the volume and function of the sexually dimorphic rat nucleus of the preoptic area

The sexually dimorphic nucleus of the preoptic area (SDN-POA) is the oldest and most robust sex difference reported in the mammalian brain and is singular for its occurrence in a wide range of species, from rodents to ungulates in passing through the man. This small collection of dense Nissl neurons is reliably larger in males.

Despite its notoriety and intense interrogation, the mechanism establishing sex difference and the functional role of SDN have remained elusive. Converging evidence from rodent studies has led to the conclusion that estrogen-aromatized testicular androgens are neuroprotective in males and that higher apoptosis (natural cell death) in females determines their smaller SDN. In several species, including humans, a smaller SDN correlates with a preference for mating with males.

Here we report that this volume difference depends on a participatory role of phagocytic microglia that engulfs more neurons in the female SDN and ensures their destruction. Selective blockade of microglia phagocytosis temporarily spared neurons from apoptotic death and increased SDN volume in women without hormonal treatment.

The increase in the number of neurons in the SDN in newborn females led to a loss of preference for male odors in adulthood, an effect parallel to an attenuated excitation of SDN neurons, as evidenced by the reduction in immediate early gene expression (IEG) when exposed to male urine.

Thus, the mechanism establishing a sex difference in SDN volume includes an essential role for microglia, and the function of SDN as a regulator of sexual partner preference is confirmed.

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