Refining the genetics of alcoholism

by Rachel Harris

The idea that alcoholism has a genetic component has gained credibility over recent decades. Previous research has studied the association of the dopamine receptor gene (DRD2) and alcoholism. However, a new study—fixing the limitations of prior research—was recently conducted. Presenting inconsistent findings, this new study claims that a neighboring gene called ankyrin repeat and kinase domain (ANKK1) may also be involved in forming addiction, including alcoholism. Working on a project for the Collaborative Study on the Genetics of Alcoholism (COGA), researchers across the United States conducted the research, which involved marking the dopamine receptor gene and other genes in the surrounding area. Using a sample of Caucasian families, the study found that the ANKK1 gene provides the strongest association to alcoholism. Although the findings of this research are extremely important to the study of genetic influences on alcoholism, they are not conclusive. The study does not prove that ANKK1 is involved in alcoholism any more than DRD2; it only shows that a strong association exists. The results “must be interpreted with caution and further explored.” [1] More studies need to be conducted to verify the results.

Furthermore, when fully exploring the psychology of addiction, it is important to look at the formation of alcoholism as a combination of genetic and social factors. Individuals are shaped both by genes and the environment. Environmental factors, such as the social skills learned from one’s family and other daily social interactions, can influence the development of alcoholism. Moreover, alcohol is a prevalent part of our culture. Forces in American society, such as advertising, can contribute to an individuals’ decision to drink. Thus, it is important to continue to research the origins of disease of alcoholism, as the development of the disease consists of complex factors.

Reference

[1] Genetic Influences on Addictions-New Findings. Medical Research News.
25 September 2007.

Neural stem cells

by Taylor Petruccelli

I came across this topic in research for another class. Hopefully it will spark some interest in our blog…

Brian Vastag of Science News reported in mid March of this year about a neurologist and his team that implanted stem cells in diseased mice to initiate the growth of various types of brain cells. These newly produced brain cell types were recorded to extend the lifespan of each originally diseased mouse by seventy percent. The neurologist was Evan Y. Snyder, a leading figure in stem cell research, especially such pertaining to the Central Nervous System. Currently employed under staff at Harvard Medical School as Assistant Professor of Neurology, Snyder completed this study and experiment over ten years ago at the Burnham Institute for Medical Research in La Jolla, California. The study entailed developing murine stem cells that would be used to propagate neurons and support cells, called astroglia and oligodendrocytes, aimed to repair and protect the brains of the mice. The mice in the experiment were infected with Sandhoff disease which is characterized by an insufficient amount of the enzyme hexosaminidase (hex). Hex aids in lipid metabolism which helps eliminate excess lipids, or fats, from the brain. Without this important enzyme these damaging lipids amass, often in children, leading to death before age ten. Sandhoff disease and around fifty other diseases, such as Tay-Sachs, are all based around this inability of the brain to rid abundant lipids. Thus, Snyder implanted stem cells at birth that would eventually reproduce daughter cells competent in restoring enzyme production. He therefore achieved in creating an embryonic stem cell that when implanted around neural cells was capable of becoming a specialized cell, in this case one to produce hex. Snyder remarked that “The implanted cells knew exactly how to repair the brain,” a comment he followed with: “Even the dumbest stem cell is smarter than the smartest neurobiologist” (Vastag, 2007).
Snyder’s study opened up possibilities to also develop a human counterpart of the murine neural stem cell (NSC). It was discovered that stem cells from human fetal brains and human embryos, along with that from the mouse brain, were proficient in curing or neutralizing the harmful effects of the murine Sandhoff disease. This understanding brought Snyder and other neurologist back on board. Correspondingly, through a strategic advancement of experimental steps, Snyder and his team mirrored the process of propagating multipotent murine NSCs with that of a human equivalent, in order to achieve similar results in creating engraftable human neural stem cells capable of curing an array of diseases and genetic defects (Vastag, 2007; Flax, 1998).
In their basic form, neural stem cells are primordial, undesignated cells employed to reproduce a variety of highly specified cells of the Central Nervous System (CNS). NSCs sustain three main abilities or uses. First, they are postulated to evolve into cells for multiple regions of the CNS, predominantly including neurons, astroglia, and oligodendrocytes. Second, NSCs are meant to propagate, or reproduce, new NSCs with equivalent potential, otherwise called self-renewing. Lastly, they have to present a therapeutically benefit to the CNS, whether through populating or degenerating a specified region. The realization that murine neural cells with stem cell attributes, created in vitro, could effectively adjust to, in this case, a mouse’s brain after implantation, sparked the interest of neurologists to discover the relevant medicinal values of NSCs. It is hoped to uncover the abilities to cure genetic defects, injuries to the CNS, congenial or acquired brain deficiencies, among many other health issues (Flax, 1998).
How neural stem cells work is to first be isolated from the embryonic source. In the mouse experiment the neural cells with stem cell properties were isolated from the murine CNS of an adult. Then the individual NSC is reproduced in vitro through multiple techniques, all of which are efficient and safe. After full cultures of NSCs are propagated, they are implanted into specific germinal zones during growth periods to encourage reproduction during the normal natural developmental stages. With abundant plasticity, ability to adapt and mold, these cells relocate themselves and begin to differentiate in a suitable means for increasingly specialized cells of the CNS. Due to the success this process has undergone in rodent experiments, its potential in the human counterpart has been long awaited (Flax, 1998).

To read further in depth on Snyder and his team’s experiments you can find his article (see references) on nature.com. However I gained access to it through the Vassar Library using Scopus (no link), so to read it you will have to look it up (sorry).

Overall:
Although Snyder accredits the success to the stem cell rather than any neurobiologist, he himself discovered something remarkable and unprecedented. Rather than trying to create specialized cells physically, he allowed science to take over with natural creation. It seems the paradox between creating a single specialized cell from the start or allowing a cell to differentiate and migrate on its own follows a seemingly unscientific adage: “You bring a man a fish, you feed him for a day, but if you teach a man to fish, you feed him for a lifetime.”

References
Flax, J. D., Aurora, S., Yang, C., Simonin, C., Wills, A. M., Billinghurst, L. L., et al. (1998).
Engraftable human neural stem cells respond to developmental cues, replace neurons, and
express foreign genes. Nature Biotechnology, 16(11), 1033-1039.
Vastag, B. (2007). Brain fix. Science news, 171(11; 11), 163-163.

What not to eat

In another post, I talked about why children are naturally picky eaters. A nice reminder of the hazards of unfamiliar foods showed up in this article. It seems that some unscrupulous fish mongers in Thailand are passing off the flesh of the notoriously poisonous puffer fish as salmon, and people are dying.

Tetrodioxin, the poison in puffer fish, is stored in its organs, not its flesh, but it only takes a few stray milligrams to kill you. It is not a pleasant death, either. First your lips get tingly and numb, then your face and extremities get numb, and eventually, you can’t move. Your brain is fine, however, so you are well-aware of what is happening until the moment of death some hours later. Carefully prepared puffer fish is actually served as a delicacy in Japan and Korea, where it only kills people occasionally.

What makes this stuff so poisonous? It is a neurotoxin, meaning that it interferes with the cells that make up our nervous system. Neurons work the same way whether they are found in humans or in the shellfish that puffer fish prey on. The job of a neuron is to send a signal from one end of the cell to the other. It does this work by an elaborate chain reaction of holes in the cell membrane opening up and shutting down. These holes are called ion channels, because they allow electrically charged molecules (ions) of sodium, potassium, calcium and chloride through them when they are open. In an action potential, what we call this chain reaction, the signal consists of the movement of ions like sodium and potassium in and out of the cell. Just a teeny bit of tetrodioxin is enough to disrupt lots of sodium channels, preventing neurons from firing. The result? Tingly lips (the sense messages are not getting through), paralysis (motor signals are not getting through) and death (the neurons that control your heart stop working).

So take a cue from those picky kids, and stay away from this exotic food.

———————————————————————————————————————–

My first take on this story was that it was a nice chance to talk about how neurons work, or don’t. But there is another level on which to think about this. The evolutionary psychology story about why children avoid novel foods makes lots of sense to me. But how does an evolutionary perspective explain why people in Japan and Korea would seek out puffer fish as a delicacy? How can we explain that from any perspective? And why is the most poisonous variety thought to be the most delicious? That is food for thought.