Brain DNA can be altered by childhood experiences

By ELAINE CHIAO | March 29, 2018

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Early childhood experiences can affect DNA state in the brain.

There is often the notion that DNA is a set of permanently stable biological sequences, but in reality, the genetic code is far more complex than most people think. 

DNA is under the constant influence of environmental factors and randomly arising mutations. Most recently, researchers at the Salk Institute discovered that DNA can also be directly modified by early life experiences.

Rusty Gage, a professor in Salk’s Laboratory of Genetics and one of the authors of the study, commented on how the team’s research supports the theory that DNA is even more dynamic than once believed.

“It turns out there are genes in your cells that are capable of copying themselves and moving around, which means that, in some ways, your DNA does change,” Gage said in a press release.

For decades, scientists have known about the existence of transposable elements, DNA sequences that are often known as “jumping genes” because of their ability to jump and relocate in between different parts of the genome through random insertions. 

For example, the most common jumping genes found in humans are called long interspersed nuclear elements, abbreviated LINEs. 

In the human brain in particular, many neuronal cells can undergo changes that are caused by LINEs. In fact, in 2005 Gage’s lab identified a type of human jumping gene called L1 that can freely move around within developing neurons.

The changes that occur as a result of DNA movement can have complicated consequences. 

On the bright side, the changes effectively increase genetic diversity, but there has been some limited evidence that suggests that these changes might also catalyze neurological conditions such as schizophrenia.

Tracy Bedrosian, a former Salk research associate and first author of the study, suggested that perhaps there are certain environmental factors that increase the frequency of DNA changes.

“While we’ve known for a while that cells can acquire changes to their DNA, it’s been speculated that maybe it’s not a random process,” Bedrosian said in a press release.

For further investigation, the team embarked on studies that tested this hypothesis. 

The team’s work focused on studying the relationship between parenting patterns and DNA changes in mice. Subsequently, they discovered that the mice offspring that received more neglectful maternal care had a higher number of L1 copies in the hippocampus of the brain.

To eliminate potential confounding variables, the team also conducted multiple control experiments that led to the same initial conclusion. 

They tested to make sure that the extra DNA was actually located in the nucleus and that the offspring did not simply inherit L1 from their parents. 

They also cross-fostered offspring such that mice born to neglectful mothers were raised by attentive ones and vice versa.

The team hypothesized from this experimental evidence that mice raised by more neglectful mothers experienced a higher level of environmental stressor that somehow triggered an increasing expression of L1 genes.

Furthermore, the researchers successfully proved that mice with neglectful mothers had a significantly lower amount of DNA methylation on L1 genes compared to those with attentive mothers.

Although the results suggest that methylation is correlated to the activity of L1 genes, it is still not known whether L1 mobility has any important functional effects. 

Interestingly, however, studies on childhood neglect in humans also showed altered DNA methylation patterns for other genes.

“That’s a hopeful thing, because once you understand a mechanism, you can begin to develop strategies for intervention,” Gage said.

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