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Shaping Minds: How the Immune System Molds Rat Brains in Development

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summary: Immune system cells in the female rat brain consume and digest neurons, which can shape specific brain regions during development and influence behavior.

This insight into the interplay between biological sex, the immune system, and brain development paves the way for understanding why certain brain disorders are more common in one sex, and future treatment or prevention. It may help your strategy.

Key Point:

  1. Immune system cells in the female rat brain consume and digest neurons to form specific brain regions during development.
  2. This process may influence behaviors such as odor preference, which is an indicator of sexual partner preference in rodents.
  3. Understanding the role of biological sex and the immune system in brain development may help explain the gender predominance of certain brain disorders.

sauce: University of Maryland

Researchers have established that biological sex plays a role in determining an individual’s risk of brain damage. For example, boys are more likely to be diagnosed with behavioral disorders such as autism and attention deficit disorder, and 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. I think it may have something to do with the difference in

Researchers at the University of Maryland School of Medicine now believe they have identified the mechanism why and how one brain region differs in size in men and women, according to a February study published in. PNAS.

A study performed in rats found that immune system cells in the female brain consume and digest neurons to sculpt this brain region during development.

The researchers also found that tweaking the size of this brain region, which forms in the first few days of life, affected whether female rats still preferred male rat odors. In rodents, this ‘odor preference’ is an indicator of sexual partner preference, with female rats usually preferring male odors.

Although these rat tendencies do not directly apply to human sexual partner preferences, the findings suggest that changes to the brain determined by the immune system can later affect behavior. is shown.

A detailed understanding of how biological sex and the immune system contribute to shaping the developing brain may one day help experts understand why certain brain diseases are more likely to occur due to gender. and may shed light on better ways to treat or prevent these conditions.

“There is a lot of overlap between the male and female brains, but it seems that it is the immune system that provides much of the natural variation. Distinguished Professor John Z. and Akiko K. Bowers.

For the current study, Dr. McCarthy and her colleagues examined regions located deep in the brain that are two to four times larger in male rats than in female rats. This size difference also appears in the brains of people in similar regions, but the gender difference is less pronounced.

A closer look at different cell types in male and female brains showed that immune cells in the brains of female rats have many surface structures called phagocytic cups that immune cells use to eat other cells. I noticed that there is

They also observed that these immune cells digested neurons. Normally, these immune cells eat debris, dead or dying cells, and cells infected with viruses and bacteria, rather than healthy brain cells.

When researchers use drugs or antibodies to block immune cells’ ability to eat neurons in the rat’s brain, this region of the female rat’s brain grows to be similar in size to that of the male rat’s brain. I discovered that

“For almost 50 years, we thought that cells died only in females, not males, and that this was due to steroid hormones.” Department of Pharmacology, UMSOM.

“In an open field where all cells are in contact with each other, we see microglial immune cells breaking through other cells and eating one specific cell. The cells these microglia eat are not random, but why?” I don’t know if they were chosen.These are the kinds of questions we still need to investigate.”

The brain regions analyzed in this study are known to control reproductive behavior in rats. For example, female rats typically prefer male rat odors and male rats prefer female rat odors when given a choice.

this shows a slice of the brain
A study performed in rats found that immune system cells in the female brain consume and digest neurons to sculpt this brain region during development. Credit: Researcher

Researchers found that females, who had larger brain regions due to blocked immune cell feeding functions, disliked male rat odors and instead preferred female rat odors or did not like them at all. .

“This finding adds to the evidence that the immune system plays a major role in determining specific 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 if this process can be manipulated to develop new treatments for autism and anxiety, but it is a promising research avenue to explore.”

Dr. McCarthy is also Director of the newly formed University of Maryland Medical Institute (UM-MIND). The Institute was founded to bring together basic and clinical scientists to make it easier to translate discoveries about the brain into new treatments for disease. brain.

Her area of ​​expertise is one of the institutional strengths of neurodevelopmental and psychiatric disorders. Other focuses of this institute are neurotrauma and brain injury, 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), National Institute on Substance Abuse (R01DA039062).

About this neurodevelopmental research news

author: Vanessa Mcmaines
sauce: University of Maryland
contact: Vanessa McMains – University of Maryland
image: Images credited to researchers

Original research: closed access.
Microglial phagocytosis mediates volume and function of rat dimorphic nuclei in the preoptic areaby Mark Gladwin et al. PNAS


Microglial phagocytosis mediates volume and function of rat dimorphic nuclei in the preoptic area

The preoptic sexual dimorphic nucleus (SDN-POA) is the oldest and most robust sex difference reported in the mammalian brain and is present in a wide range of species, from rodents to ungulates to humans. It is peculiar. This small collection of Nissl-dense neurons is reliably larger in volume in males.

Despite its notoriety and intense interrogation, both the mechanisms that establish sex differences and the functional role of SDN remain elusive. Converging evidence from rodent studies suggests that testicular androgens aromatized to estrogen are neuroprotective in males, while higher apoptosis (spontaneous cell death) determines smaller SDNs in females. We have come to the conclusion that in some species, including humans, smaller SDNs tend to favor mating with males.

Here we report that this volumetric difference depends on the participating role of phagocytic microglia in engulfing more neurons in the female SDN and ensuring their destruction. Selectively blocking microglial phagocytosis transiently spared neurons from apoptotic death and increased her SDN content in hormone-naive women.

Increasing the number of neurons in the neonatal female SDN leads to a loss of preference for male odors in adulthood, as evidenced by decreased immediate early gene (IEG) expression when exposed to male urine. In addition, it had a parallel effect of attenuating the excitation of SDN neurons.

Thus, the mechanisms that establish sex differences in SDN volume include an important role for microglia, confirming the function of SDN as a regulator of sexual partner preference.

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