Brain's 'gender' may be quite flexible: Mechanism that plays key role in sexual differentiation of brain described
Date:March 31, 2015 Source:University of Maryland Medical Center/School of Medicine Summary:During prenatal development, the brains of most animals, including humans, develop specifically male or female characteristics. But scientists have known little about the details of how this differentiation occurs. Now, a new study has illuminated details about this process. Researchers succeeded in transforming the brain of a female rat after an important developmental window had closed, giving it the characteristics of a male rat brain.
Scientists altered rats brains. "Physically, these animals were females, but in their reproductive behavior, they were males," said Nugent. (stock image) Credit: © vitals / Fotolia
During prenatal development, the brains of most animals, including humans, develop specifically male or female characteristics. In most species, some portions of male and female brains are a different size, and often have a different number of neurons and synapses. However, scientists have known little about how this differentiation occurs. Now, a new study by researchers at the University of Maryland School of Medicine (UM SOM) has illuminated details about this process.
Margaret McCarthy, PhD, professor and chairman of the Department of Pharmacology, studied brain development in newborn rats.
She found that giving estradiol, a testosterone derivative, triggers a mechanism by which certain genes in the brain are "unsilenced," allowing them to initiate the process of masculinization. This process involves a group of enzymes known as DNA methyltransferases, or Dnmts, which modify DNA to repress gene expression.The paper was published in the latest issue of the journal Nature Neuroscience.
"Nobody has ever shown that this is how the process works," said Prof. McCarthy. She collaborated with Bridget Nugent, PhD, who is now a researcher at the University of Pennsylvania.
"This gives us a new understanding of how gender is determined in the brain."Prof. McCarthy and Nugent also found that inhibiting Dnmts has powerful effects, even outside the usual window of development. During prenatal development there is a restricted time frame during which the brain takes on male or female characteristics. Scientists had thought that once this window closed, it could not be reopened. But the two researchers found otherwise. They succeeded in transforming the brain of a female rat after the window had closed, giving it the characteristics of a male rat brain.
Prof. McCarthy and Nugent injected Dnmt inhibitors into a specific region of the female brains, a region known as the preoptic area, or POA. In every species that's been studied, including humans, the POA plays a key role in governing male sexual behavior. The injections occurred after the first week of birth, the time when the window for brain sexual differentiation was thought to have been closed. Despite this, the preoptic area in these animals was transformed, and took on structural characteristics of a male rat. The female rats also behaved differently, displaying sexual behavior typical of male rats. In another experiment, they genetically deleted the Dnmt gene in female mice; these animals also showed male behavior patterns.
"Physically, these animals were females, but in their reproductive behavior, they were males," said Nugent. "It was fascinating to see this transformation."For the entire article > > >
https://www.sciencedaily.com/releases/2015/03/150331121249.htm