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Dan Rather: I am here with Dr. Tameka Lundy a neuroscientist at Emory University. Dr. Lundy has just completed a study on stress and her lab was successful in finding the genetic component that causes stress.
Dr. Lundy how are you doing today?
Dr. Lundy: I am fine Dan and yourself
Dan Rather: Just fine. Now tell all of our viewers out there watching what your research entailed and how you went about performing the research.
Dr. Lundy: Well let me first start with defining stress. Stress is a feeling of tension that is both emotional and physical. However what many people fail to realize is that stress is a risk factor for a variety of illness, ranging from auto-immune disorders to mental illness. Our lab has unlocked the mystery behind this silent killer that effects more than half of American. I feel that the result of stress is due to early maternal care and environmental affects later on in life.
Dan Rather: This study wasn’t performed on humans. So what model did you use in your study?
Dr. Lundy: Well Dan in the beginning we used a model that supports the correlation of stress to early maternal care. This model is the environmental regulation of the development of responses to stress in postnatal handling research with rodents. In this model, there is a brief separation daily of the pup from the mother. In the rat and mouse, postnatal handling decreases the magnitude of behavioral and endocrine responses to stress in adulthood. While longer periods of daily separation from the mother increase behavioral and endocrine responses. Behavioral and endocrine responses to stress are largely governed by two central corticotropin-releasing factors (CRF) neuronal populations. However environmental manipulations can alter expression of behavioral and endocrine responses to stress by altering the development of central CRF systems as well as systems that regulate CRF activity.
Dan Rather: You also worked with non-human primates. Can you elaborate on your findings and your studies dealing with them?
Dr. Lundy: Actually Dan for the last year I have been conducting my study on voles, however I did do some collaboration with another neuroscientist at the Yerkes Primate Center who studied the rhesus monkey. But like I said I worked with voles for the past few months. Voles are mice like rodents, which demonstrate complex behavior. For several months I studied the behavior of the voles and looked at the gene expression of two vital neuropeptide’s whose central pathways have been implicated in a number of social behaviors. Oxytocin and vasopressin only differ in structure from one another by two amino acid positions. Oxytocin plays a role in the induction of maternal behavior while vasopressin is associated with male behavior. The effects of vasopressin are mediated by the vasopressin V1A receptor. In the prairie vole V1A receptor contains a microsatellite insert in the 5’ flanking region of it’s promoter. There is a correlation between promoter sequencing and the binding of the V1A receptor, the lon
ger the promoter sequence the less receptor binding. Oxytocin too is mediated by a receptor called the oxytocin receptor(OTR). It too has a microsatellite in the 5’ flanking region of its promoter. In collaborating with the other PI at Yerkes we found that this was also similar in the rhesus monkeys. As far as the two neuropeptides go.
Dan Rather: Do these two neuropeptides have other functions?
Dr. Lundy: Yes they do, vasopressin is involved in homeostasis and oxytocin allows women during labor to contract. However their other functions aren’t essential to this study. I focused solely on the V1A receptor and did studies to link the length of the promoter sequence to the binding pattern of the receptor. I hypothesized that the length of the promoter sequence of the two receptors had a direct correlation on the social behavior that they exhibit. As I said before the longer the promoter sequence the less receptor binding. This was a very important discovery because the binding of vasopressin to the V1A receptor is what causes the ultimate expression of the gene and behavior exhibit by the animals. My lab and I genotype several generations of prairie voles based on the promoter region of their V1A receptor. Based on the laws of Mendel each child receives one allele from their mother and one from their father. This is always true unless there is a mutation or a sex-linked gene. Besides looki
ng at gene’s we observed their behavior. Ranking their behavior on a scale of 1-10. Ten being the highest in which the parents licked and groomed their pups constantly and one being the lowest in which there was seldom licking and grooming.
Dan Rather: Can I just ask you this question, while I was reading your article I was under the impression that prairie voles were known for their bi-parental care so how could there be seldom licking and grooming?
Dr. Lundy: That is true Dan however we based this ranking relative to the other voles. So the amount of parental care that was giving was a substantial amount however it wasn’t ranked as high as others. So based on this ranking our findings were astonishing. We looked at the genes of the offspring when they were just pups. As suspected they all inherited one allele of the vasopressin gene from their mother and one from their father. However when they reached adulthood those animals that were highly groomed and licked their gene expression didn’t change it was the same as when they were younger. However those offspring that ranked low on the licking and grooming chart 90% of their short allele had changed. This was a great finding. What this tells us is that the environment can change the expression of the gene. This was only seen in those offspring in which they weren’t licked and groomed as much as they could have been. Then there was a correlation between those animals who were ranked highly on
the licking and grooming chart but weren’t sibling, The length of their promoter gene was within 1 basepairs of one another and when we sequenced their genes they were exactly the same with one or two differences in nucleotides. This is really amazing because this is the first study in which the genotype and behavior where looked at in correlation with one another. We also looked at their brains and looked at the location of the V1A receptor. All animals which ranked high in licking and grooming they had an overwhelming amount of VIA receptor in their ventral palladium. The location of the VIA receptor is what distinguishes the montane voles which aren’t monogamous and the prairie vole which are monogamous.
Dan Rather: How could this help out the millions of Americans that suffer from stress?
Dr. Lundy: That is a good question. Well the biggest problem seems to be that those that experience stressful lives are due to their treatment when they were younger. What is good is that the environment can reverse that treatment in a positive way or it can cause a negative change. The pups that were not licked and groomed as much have a much greater chance of being influenced by their environment and peers. This can pose a problem and that’s what we would like to solve and what I think we have solved. Of course fostering would solve that problem but that’s not an ideal solution. So we know that you are going to inherit that gene from your parent so what we did was take a female offspring that didn’t receive a high ranking on the behavioral chart. We cloned a gene from an ideal female, which ranked high on our behavior chart. We inserted that cloned gene into a plasmid and then inserted that plasmid into the female that didn’t receive a high ranking. When that animal was mated with another male
of very high ranking the offspring’s V1A gene remained the same throughout life. When the female was mated with a male that ranked low on the behavior chart the offspring’s V1A receptor remained the same throughout life. What this tells us is that the mother is the primary care giver and regardless of the father’s length or sequence if the mother express behavior that gives the pup a nurturing early environment the father will mimic that behavior and the "stressful" gene that he passes on to the child will be over come by the early nurturing of the parents. Our lab has been working with a pharmacy company to come up with a compound that will have an effect on the expression of the V1A receptor gene in the brain. This compound is currently being treated in non-human primates and has been effective. They haven’t tested this on humans but it’s only a matter of time.
Dan Rather: Thank you Dr. Lundy. This is Dan Rather with 60 minutes have a good night.
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