A few months ago, I posted about an article which speculated that the evolution of the modern human brain was a result of Lamarckian evolution. To recap — this means that a trait is acquired during one’s life experience, and that trait is transferred to the offspring. The classic example is that giraffes have long necks because a precursor animal stretched its neck to reach high foliage, the next generation was born with longer necks because of its parents’ reaching. The next generation reached yet higher, and the next generation had yet longer necks. In humans, the example is something like a blacksmith has big muscles from working at a forge all day, he passes on his big-muscles to his son because of the use of his arms.
For something like brain development to be influenced by life experiences, I speculated that hormonal changes (e.g., corticotropin release hormone, ACTH, cortisol, norepinephrine) as a result of psychological stress or trauma would have to induce epigenetic changes in sperm.
Imagine my surprise when I directed my web browser to Nature News where researchers at the Brain Research Institute at the University of Zurich discovered that specific microRNAs were indeed increased in the sperm of male mice exposed to psychological trauma (being forced to be away from their mother during rearing, who was undergoing stressful experiences, i.e.: cold-stress or forced swimming)…. and these microRNA increases persisted for yet one more generation, and also was increased in their hypothalamus and cortex. So this is one interesting piece of the puzzle. The Pubmed Link.
They do not yet know the mechanism of the microRNA-induced changes. But there are several steps that need to be taken to be sure that the observed effect is real, and a few grains of salt.
- The study used high-throughput analysis, and screening-type methodologies. These should always be followed up with low-throughput analyses because the reliability of any one target in a high throughput screen of RNA quantity is low. We did this with our PLOS One study. We used a different methodology to quantitate a panel of several microRNAs from our high throughput screen which quantitated 380. We chose some that were up, some that were down and some that were not different. We plotted the signal in the single-target method vs. the high-throughput method to validate that they matched. This, in my opinion, is a must-do, if you plan to make a claim about any one transcript.
- The mechanism is not understood. How do the microRNA’s change in the sperm? One good place to start would be to look at the promoter region for the candidate microRNAs that were altered — are these transcription factor sites or hormone response elements (e.g., that would respond to cortisol)? Are there methylation sites?
- The next additional step is to show that changing the concentrations of those microRNAs has some effect on prenatal CNS development.
This topic is very near and dear to my own research plans and goals. I’m going to recreate here a figure that I used to illustrate the point of the FKBP5 gene. This protein’s function is to modulate the glucocorticoid receptor nuclear translocation, it essentially inhibits it; so it serves as a feedback mechanism for particular cells to “turn off” cortisol signaling very quickly after it starts. But if FKBP5 is too high … no cortisol signaling was allowed in the first place. There are gene polymorphism in FKBP5 associated with major depression … and one of my future research plans is to determine the big how and why. One potential way is by altering microRNA response element sequences. …. aaaand it comes full circle. I would be interested to know of any of the microRNAs discovered to be changed in the sperm of traumatized male mice might also bind to FKBP5. Cool stuff, huh?