Let’s start this day’s column off with a somewhat famous story of two rats.
Once upon a time, some scientists decided to study a couple of baby rats (what a surprise!) One baby rat received a great deal of attention from its mother as she licked its fur many times a day. The other baby rat was neglected most of the time: its mother rarely licked its fur. The two rats grew and began to behave in very different ways compared to each other.
The rat which had received all the licking (the love, the nurturing) was not easily startled, showed more curiosity by exploring places away from its mother, and did not suffer surges of stress hormones. The rat which had been, for the most part neglected, was easily startled by noises, was reluctant to explore away from its mother, and suffered surges of stress hormones.
Hundreds of lab experiments have duplicated these results and these findings have been extrapolated to humans via further brain-based research.
Our brains develop according to a formula encoded in our genes – our inheritable factors. “Each of our brain cells contains the same set of genes we are born with and uses those genes to build proteins and other molecules throughout its life. The sequence of DNA in those genes is pretty much fixed. For experiences to produce long-term changes in how we behave, they must somehow” (1) be able to do something akin to rewriting the genes in our brains.
Thousands of molecules attached to our DNA shut some genes down while allowing others to be active. These molecule switches, it turns out, can be rearranged by our experiences. This changes the way our brain cells work.
“Two families of molecules perform that kind of genetic regulation. One family consists of methyl groups, molecular caps made of carbon and hydrogen. A string of methyl groups attached to a gene can prevent a cell from reading its DNA sequence. As a result, the cell can’t produce proteins or other molecules from that particular gene. The other family is made up of coiling proteins, molecules that wrap DNA into spools. By tightening the spools, these proteins can hide certain genes; by relaxing the spools, they can allow genes to become active.
Together, the methyl groups and coiling proteins – what scientists call the epigenome – are essential for the brain to become a brain in the first place. An embryo starts out as a tiny clump of identical stem cells. As the cells divide, they all inherit the same genes, but their epigenetic marks change. As division continues, the cells pass down not only their genes, but their epigenetic marks on those genes. Each cell’s particular combination of active and silent genes helps determine what kind of tissue it will give rise to – liver, heart, brain, and so on. Epigenetic marks are remarkably durable, which is why you don’t wake up to find that your brain has started to turn into a pancreas.”(2) (Based on the current wave of cinematic sci-fi thrillers, though, perhaps this concept is not a bad idea for a movie: doctors race against time to ensure that everyone’s brains do not become livers. How will they stop the epidemic!)
A lack of folate available to a developing fetus from its mother’s body is a nutritional factor that can change epigenetic marks prior to birth. Another nutritional factor which can also effect a change to the brain in utero occurs when the mother consumes a lot of alcohol. After birth experiential factors can change the epigenetic marks in the brain as evidenced by the rat experiments.
Neurons in the hippocampus – a part of the brain which helps organize memories – regulate the response to stress hormones by making special receptors. “When the receptors grab a hormone, the neurons respond by pumping out proteins that trigger a cascade of reactions. These reactions ripple through the brain and reach the adrenal glands, putting a brake on the production of stress hormones.”(3)
It turned out (in more rat experiments) that the stretch of DNA that works as the switch for one of the hippocampus’ genes, the glucocorticoid receptor gene, was different in the rats which received many licks compared to the rats which received very few. In the latter group, the molecule switch for the glucocorticoid receptor gene was capped by methyl groups. The neurons, therefore, could not produce as many stress receptors. “The hippocampus neurons were, therefore, less sensitive to stress hormones and were less able to tamp down the animals’ stress response”(4).
And, the neglected rats – the ones which received few licks – were permanently stressed out as a result. And, that's the end of the story of two rats.
D.
(1-4) were taken from an article by Carl Zimmer published online June 16, 2010. The article was originally from the June 2010 issue of Discover magazine.
