Friday, October 19, 2012

Early environments, parental care, and the importance of touch

The conditions that we experience early in life can have profound effects on our future physiology. For example, during the winter of 1944 the Netherlands suffered a famine because the Germans blockaded food and fuel from reaching the country. Mothers who were pregnant during this time gave birth to babies that had thrifty metabolisms, which unfortunately led to a high rate of diabetes, obesity, and other problems for these "Dutch Hunger Winter" children. Because the prenatal environment was nutritionally lacking, it made sense to shift towards a thrifty metabolism, but when the environment changed a thrifty metabolism phenotype proved to be detrimental. But what the Dutch Hunger Winter children proved is that our physiology is plastic during early life, and that conditions during this time will influence our future physiology.

In addition to affecting metabolism, early life nutritional states can also influence other physiological parameters. Zebra finch chicks grow at a slower rate if their parents are inattentative and do not feed them often enough. If brood sizes are enlarged (which causes chicks to face increase competition for food), barn swallow chicks will have decreased immune responsivness as adults and male collared flycatchers will face decreased, future reproductive output. While these examples all show that adequate nutrition is important for young animals, they also show that the quality of parental care can play a large role in physiological development.

Touch is another component of parental care that has been shown to profoundly affect post-natal development in mammals. This was shown in a very crude experiment by Emperor Frederick the II of Sicily (reign 1220-1230). Frederick wanted to know what language was the "natural" language of humans, so he devised an experiment where he had some infants placed in isolated rooms where they would be unable to hear any human speech. Maids were hired to clean and nurse the babies, but the maids were not allowed to spend any more time than necessary with the infants in case they accidentally talked in the infants presence. Frederick believed that when the infants reached an age where they could talk, they would reveal the "natural" human language (most likely, he thought, Latin or Greek). What happened instead was that all the infants languished and died. And so we now know that if babies are deprived of touch, if they are denied love and affection, they will most surely die very young. (Here's a happier research example on the importance of touch; premature infants are often placed in fancy incubators because they need special respiratory equipment, protection from infectious diseases, etc. But even with this special care, many infants still fail to thrive or require longer recovery times than expected. However, by gently stroking an infant's legs and arms for just a few, short periods everyday, researchers found that growth rates increased by 50%!)

Researchers have also shown that touch is very important for the development of young rats. Rat pups that are not licked and groomed enough during the first week of life will develop hyperactive stress responses, meaning that these pups will have high corticosterone (CORT) levels in response to stressors. Additionally, these pups will have poor negative feedback, which means that it will take them longer to decrease their CORT levels after responding to a stressor. Overall, pups from low-licking and grooming mothers will be exposed to more total CORT during their lifetimes, which may make them more susceptible to stress-related pathologies. Which leads us to this question; how does low-licking and grooming cause pups to develop hyperactive stress responses?

A hyperactive stress response is characterized by high stress-induced CORT levels and poor negative feedback. Poor negative feedback is often due to low levels of CORT receptors (think about it this way; during a stressor an animal has a surge in CORT, but after the stressor passes they need to decrease CORT production. Parts of the brain know when to shut down CORT production based on how many CORT receptors are bound. So, if you have fewer receptors, it takes longer for enough CORT receptors to be bound so the brain "knows" when to shut off CORT production).

OK, so pups with hyperreactive stress responses must have lower levels of CORT receptors, and this is exactly what Liu et al. (1997) found. However, CORT receptors are not permanent fixtures- they are constantly being recycled all throughout the body, so how can an event early in life cause a permanent change in receptor expression levels? The answer is at the level of the gene; basically, conditions early in life can affect how accessible the CORT receptor gene is to transcription. Weaver et al. (1997) found that the promoter region of the CORT receptor gene was highly methylated in the hippocampus. DNA methlyation occurs when a cytosine is converted into 5-methlycytosine, and this conversion makes it more difficult for transcription factors to bind to the promoter region, thus inhibiting transcription.

Another interesting thing about pups from low-licking and grooming mothers is that they will grow up to be low-licking and grooming mothers themselves. An elegant experiment by Francis et al. (1999) showed that the low-licking and grooming trait is inherited through behavioral processes, not genetic processes. Basically, Francis et al. (1999) took pups from low-licking and grooming mothers and switched them with pups from high-licking and grooming mothers (this is called a "cross-fostering study"). When the pups grew up, their own licking and grooming frequency was determined by the licking and grooming behavior of their foster mother, not their birth mother. The low-licking and grooming trait is thought to pass behaviorally because it's been shown that increased levels of CRF (corticotropin releasing factor, an important stress hormone that stimulates release of ACTH which then causes increased secretion of CORT) inhibits maternal behavior.

For further reading: As always, I highly recommend the book "Why Zebras Don't Get Ulcers" by Robert Sapolsky (I shamelessly borrowed his examples of Emperor Frederick II, premature babies, and the Dutch Hunger Winter children). Some great, foundational papers on maternal effects on the development of the mammalian stress response include; Liu, D. et al. 1997. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277:1659-1662. Francis, D. et al. (1999). Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286: 1155-1158. Weaver et al. Epigenetic programming by maternal behavior. Nature Neuroscience 7:847-854. 

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