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Your Early Life Experiences Could Influence DNA in Your Adult Brain: Nurture Over Nature?
“This finding agrees with studies of childhood neglect that also show altered patterns of DNA methylation for other genes.” –Tracy Bedrosian
(LaJolla, CA) -- “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,” says Tracy Bedrosian, a former Salk research associate and first author of the study. “Maybe there are factors in the brain or in the environment that cause changes to happen more or less frequently.”
To find out, Gage, Bedrosian and colleagues began by observing natural variations in maternal care between mice and their offspring. They then looked at DNA from the offspring’s hippocampus, which is involved in emotion, memory and some involuntary functions. The team discovered a correlation between maternal care and L1 copy number: mice with attentive mothers had fewer copies of the jumping gene L1, and those with neglectful mothers had more L1 copies, and thus more genetic diversity in their brains.
To make sure the difference wasn’t a coincidence, the team conducted a number of control experiments, including checking the DNA of both parents of each litter to make sure the offspring didn’t just inherit their numbers of L1s from a parent, as well as verifying that the extra DNA was actually genomic DNA and not stray genetic material from outside the cell nucleus. Lastly, they cross-fostered offspring, so that mice born to neglectful mothers were raised by attentive ones, and vice versa. Initial results of the correlation between L1 numbers and mothering style held: mice born to neglectful mothers but raised by attentive ones had fewer copies of L1 than mice born to attentive mothers but raised by neglectful ones.
The researchers hypothesized that offspring whose mothers were neglectful were more stressed and that somehow this was causing genes to copy and move around more frequently. Interestingly, there was no similar correlation between maternal care and the numbers of other known jumping genes, which suggested a unique role for L1. So, next, the team looked at methylation—the pattern of chemical marks on DNA that signals whether genes should or should not be copied and that can be influenced by environmental factors. In this case, methylation of the other known jumping genes was consistent for all offspring. But it was a different story with L1: mice with neglectful mothers had noticeably fewer methylated L1 genes than those with attentive mothers, suggesting that methylation is the mechanism responsible for the mobility of the L1 gene.
“This finding agrees with studies of childhood neglect that also show altered patterns of DNA methylation for other genes,” says Gage, who holds the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases. “That’s a hopeful thing, because once you understand a mechanism, you can begin to develop strategies for intervention”
The researchers emphasize that at this point it’s unclear whether there are functional consequences of increased L1 elements. Future work will examine whether the mice’s performance on cognitive tests, such as remembering which path in a maze leads to a treat, can be correlated with the number of L1 genes.