Epigenetics and Drug Habituation

Science Magazine published an article that began by investigating epigenetic effects of maternal behavior in rats (Miller, 2010), and further discussed epigenetic effects in rats related to drug addiction. Last week we spoke of how epigenetic modifications linked maternal care to stress response in rats. The article continues to elaborate on other epigenetic research conducted in rodents, specifically that undertaken by Eric Nestler. Nestler's studies have concluded that in rodents, cocaine creates epigenetic changes in the genome that, "make the brain more sensitive to the next dose," as stated by Nestler (Miller, 2010).

Nestler administered cocaine in the rat model and identified that repeated administration caused suppression of methylation on a specific histone. This suppression occurred within the nucleus accumbens, responsible for pleasure and reward in our brain.

But what does this suppression cause?

Suppression of methylation on this histone in rats that had never been exposed to cocaine resulted in a growth of extra dendritic spines. 

These spines extend off the dendrite of a neuron and are what causes the neurons to be more sensitive.

Nestler also found that suppression of methylation on this histone increased rats yearning for cocaine after they had finally tried the drug.

Stop! What if instead of suppressing methylation we enhanced methylation?

Nestler researched this as well. He found that enhancing methylation of that histone reduced rats yearning for cocaine.

Unfortunately for us, Nestler states in the article that any applications of this in human drug addicts are far from completion. Although these epigenetic changes are a key link into formulating new addiction treatments.





Reference:

Miller, G. (2010). The Seductive Allure of Behavioral Epigenetics. Science Magazine, 329 (5987), 24-27. doi: 10.1126/science.329.5987.24

Pictures all accessed 28/03/2015 and referenced from top to bottom of blog entry:
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Epigenetics and Maternal Behavior

Science Magazine published an intriguing article overviewing multiple scientists' research on the relationship epigenetics has on maternal behavior in rats (Miller, 2010). This article expands on various topics and thus will be investigated in part this week, and then again next week. The article begins by exploring the research done by Michael Meaney and Moshe Szyf, published in Nature Neuroscience (Weaver, 2004). Rats vary in ways they nurture their pups - some mothers provide easy accessibility to milk and groom their young frequently, and other mothers do not spend as much time with their pups. Rats interactions between pups and their mothers were monitored. Scientist Michael Meaney determined in 2004 that, after various stress inducing tests, pups raised by mothers that provided less nurturing did not respond to stress as well as the others (For example exhibited a surge of cortisone when the rat was placed in a confining tube).

Meaney concluded that this stress sensitivity was because of a reduction in glucocorticoid receptors caused by DNA methylation of a particular gene. Methyl groups on a particular site blocked the transcription of the gene and thus production of more receptors could not be achieved.

Therefore, neglectful maternal care resulted in specific alterations in receptors that were involved in response to stress, affecting genes in a long term way. Maternal neglect caused changes in gene expression that made offspring anxious and worse at handling stressful situations.

It is difficult to grasp that the innocent rat pup's genetics were physically altered by less frequent parenting behavior, and this caused neurological differences compared to the other pups. With such a dramatic outcome, could it be possible to reverse the affects the mother rats instilled on their pups? Science Magazine claims, "Subsequent experiments showed that enzymes that reverse DNA methylation of the glucocorticoid receptor gene also reverse the effects of unenthusiastic mothering on the offspring’s hormonal and behavioral responses to stress" (Miller, 2010, pg. 25). Reversal due to particular enzymes proves to be a promising future for the rat pups. If it is possible that maternal behavior neurologically affects the rat pups, could it be that this occurs in human children as well? (Figure 1). While this has not been studied as in depth as in rats, these findings may play a key role in the pharmaceutical industry and our understanding of drugs. This topic is also discussed in Science Magazine's article and will be explored more next week. 

(Figure 1. Adapted from "The Seductive Allure of Behavioral Epigenetics" by G. Miller, 2010, Science Magazine, 329 (5987), 25) 

Reference:

Miller, G. (2010). The Seductive Allure of Behavioral Epigenetics. Science Magazine, 329 (5987), 24-27. doi: 10.1126/science.329.5987.24

Weaver IC, C. N., Champagne FA, D'Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ. (2004). Epigenetic Programming by Maternal Behavior. Nature Neuroscience, 7(8), 847-854. 

Pictures: [From top to bottom of entry] All accessed 22/03/2015.

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http://www.humane-endpoints.info/eng/images/stories/fotos/restraining_tube_rat.jpg

http://www.visembryo.com/images/rat%20mother%20and%20pups.jpg

"The Seductive Allure of Behavioral Epigenetics" by G. Miller, 2010, Science Magazine, 329 (5987), 25

Epigenetics Overview

Epigenetics Overview

Darwin coined that evolutionary change be due in part to genetic variation and heritability. The concept of passing genes to a future generation and changes in the genetic sequence, are typically understood as occurring within the genotype and thus DNA sequence. Genetics refers to the gene sequence within our chromosomes, on contrary epigenetics is other factors that control gene expression. Epigenetics is the study of cellular and trait variations that do not occur because of a change in the DNA sequence and cause heritable changes in gene expression. In short, epigenetics investigates changes in the phenotype without a change in the genotype. Both DNA methylation and histone modification have been noted as mechanisms that result in epigenetic change since the modification does not affect the DNA sequence. These modifications determine how much or whether a gene is expressed in your body. Since these epigenetic changes are heritable, they can also impact evolution.  

Prior to roughly 1970, it was widely believed that certain behaviors or choices were not heritable to future generations, although that has been disproven through epigenetic studies. For example, a person that smokes and overeats could pass that epigenetic information to their offspring. Some epigenetic information is lost and replaced with different information to the future generation, although some may remain. Therefore that person who smokes and overeats may only pass on the trait of smoking, while the trait of overeating was lost. This is all due to which genes are expressed through epigenetics. The DNA methylation may "turn on" particular genes or the histone may contract to hide particular pieces of DNA. 

This implies that behaviors or occurrences in the parents' environment could drastically affect the genetic expression of their children. Studying epigenetics can help our understanding of gene expression and how to regulate gene expression. This understanding could lead to scientists silencing epigenetic expression of unfavorable genes such as those that could lead to cancers. It also implies that our DNA (genetic material itself) is not the only factor of "who we are" and that environment does play a key role in gene expression. Epigenetics is a new field of study that will impact future generations and potentially enhance their lives.