Thursday, March 01, 2007

Genes to Behavior

How is it that some drugs change our behavior? C. Wang and his co-researchers have pried into the effects of the drug jujuboside (JuA) on the central nervous system, specifically the hippocampus (JuA is commonly used to alleviate insomnia and anxiety). In order to test JuA’s effects, Wang and his research team monitored the activity of mice given a treatment (JuA) or a placebo. Results confirmed that mice given the treatment became less active than those in the non-treatment group. In order to analyze the effects of JuA on gene regulation, researchers also performed a differential display polymerase chain reaction (PCR); a complex procedure that identified the genes that were highly expressed by the effects of JuA. The results of this test indicated increased expression of the RPGRIP1 gene (retinitis pigmentosa GTPase regulator interacting protein). The introduction of JuA to the central nervous system seems to be correlated with increased gene expression of RPGRIP1, a retinal protein normally located in the eye. The function of this retinal protein in the brain is questionable, as it may be involved in the inactivity observed in mice given the JuA treatment.

The presence of this retinal protein (normally located in photoreceptors) in the hippocampus doesn’t make sense, unless it acts in unknown neuronal pathways. On this subject R. Roepman (through independently conducted research) stated that:

“Analysis revealed the existence of another novel protein with high homology to RPGRIP1, KIAA1005, which is expressed highly in the brain. These proteins might be part of a novel family of proteins with vesicular transport-associated properties and neuron-specific function.”

The KIAA1005 protein has a structure that is very similar to RPGRIP1. Roepman proposes that the similar structure of these proteins may give some insight into their function in the cell. The overall structure of these proteins can be broken down into component regions, or “motifs”, that have highly conserved functions in the cell. One such region of RPGRIP1 , the C2, is commonly involved in intracellular transduction/ communication. Another coiled-coil domain of RPGRIP1 is presumed to be involved in intracellular trafficking. Together these sub-regions of the protein allow for communication, and transportation of materials within the cell. In summary, the introduction of JuA to the neuron causes increased expression of RPGRIP1, a protein with conserved regions that are involved in cellular communication and transportation. These protein facilitated communications may account for physical changes in the neuron that change behavior.

It seems possible that the intracellular trafficking/ transduction motifs observed by Roepman, would reinforce the activity of RPGRIP1 in the hippocampus (as observed by Wang). Although trafficking and transduction are integral to all cell function, the activity of RPGRIP1 in the neuron (given its structure) seems highly appropriate. Although Roepman and Wang have made some headway into the subject, the exact function of RPGRIP1 (and related proteins) is unknown. It is remarkable however that exposure to JuA may result in gene expression of a protein whose inherent conformation may induce intracellular communications in the neuron, possibly resulting in a behavioral modification (perhaps by changing synaptic interactions). When marrying both Wang and Ropeman’s research, this complex interaction doesn’t seem impossible.

Posted by AKE






4 Comments:

At 5:59 PM, March 04, 2007, Anonymous Anonymous said...

This article seemed very interesting at first, but the way it explained and linked scientific concepts was hard to follow. Take gel electrophoresis and PCR for instance. The way in which they are explained makes sense for someone whom would already be familiar with them, but would confuse anyone else. I feel that going into a great amount of detail on something that isn't necessarily useful to the main argument makes it confusing, or gets ‘off-topic’. I needed to reread this article and read through the intense scientific detail in order to fully understand it. It seems as though the main argument comprises of two parts, one being Wang’s discovery and the other R. Roepman’s, and that combining them might be the answer as to how drugs affect genes, which in turn affect behavior. I think this concept is worth more detail and should be the main idea in this article.
Benhayo6

 
At 8:56 PM, March 04, 2007, Anonymous Anonymous said...

This blog is on a very interesting subject, and the science behind the test is intersting as well. For the average reader I believe the results of the test, what the drugs did and how successful they were would be a better topic to discuss. The methods of the tests was interesting and well written but not as interesting as the reasons for the tests themselves. The combination of Wangs and Roepman's work is confusing as well, I didn't fully understand how the two were related, maybe more information about that would be helpful.

 
At 10:31 PM, March 04, 2007, Anonymous Anonymous said...

the topic was interesting and very informative but i agree with benhayo that it was too hard to follow and i also had to read it a couple times there was great evidence supporting the idea of how the drug could affect genes which made me think of other drugs like for add and how that effects behavior overall though the article was very scientific journal like and that there could have been more information on the behavior modification and the connection between roepman and wang was well done

 
At 11:15 AM, March 10, 2007, Blogger Unknown said...

I thought this blog had a very interesting subject, because the current mentality of most people is that a pill can cure everything, and if anything is wrong they should just take a pill. This sometimes leads to many bad side effects, which are worse than the problem trying to be fixed.
I know the point of this blog was to discus how expression of different genes modify our behavior, however I would like to discuss some other issues stemming from the results of this study.
In this case, the drug JuA did result in the expression of several genes which normally were not on. The one thing that the author did not talk about is what the finding of these 2 studies mean for people actually taking JuA. How did this affect them, and maybe what are some of the long term effects? I was also wondering what the results of the research done by the FDA were.

ivanr6

 

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