Targeting Targets: Antidepressants

      When you eat medicine for whatever reason, you expect it to take effect sooner rather than later. What you really want is for that headache, stomachache, backache, life-ache to go away quickly so you can get on with your life. But, for people who suffer from bipolar disorder or depression, there is no such thing as a quick fix like fast acting TUMS. People who suffer from these neurological diseases take medications known as antidepressants, to help counteract and fight off the depressive symptoms associated with the diseases. For a good amount of people, however, the depressive episodes can make the individual suicidal, and at that point, getting immediate help through medication won't help. This is why research has been looking at different, better targets to help the suffering individual faster than the 2-3 weeks it normally takes antidepressants.   

       In a Scientific American article, Julianne Chiaet address this topic by highlighting research being conducted that looks at current targets and better targets. Chiaet talks about a researcher, Dr. Julie Blendy, who looked at CREB and subsequently CREM. These two proteins interact commonly by binding to DNA in the cell and affecting the transcription of other proteins in their respective pathways. Chiaet notes in the article that CREM has been known to play a role in the effect of antidepressants and so Dr. Blendy wants to look at what kind of role exactly. It turns out that, according to Dr. Blendy, CREB elimination led to the up regulation of CREM, and CREM increase alone led to quicker antidepressant effects. Hence, Dr. Blendy wants to look at how CREM might be playing a role in quickening the effects of the antidepressants and possibly targeting proteins that lead to CREM's up regulation.   

     Another interesting role of CREB was presented in a lecture by Northwestern PhD candidate, Xiao-Wen Yu, who looked at what role CREB played in aging and cognitive performance. In the scientific literature, CREB is known to play a role in memory, so Yu looked at how the levels of CREB changed in aged rats and what those changes in levels of CREB meant for behavior in a variety of tests. Moreover, Yu looked at rats' performances in the Morris Water maze and in fear conditioned learning as well. She showed that increased levels of phosphorylated CREB (pCREB) led to better performance in spatial learning and memory and that levels of pCREB are only decreased in the aged rats in a specific region of the hippocampus, the CA1. All in all, she showed that the aged population was benefitting with increased levels of pCREB.   

     It was interesting to see how varied the effects of CREB could be. Both articles showed its importance in the brain but on different levels. Moreover, CREB, with CREM, seems like it's playing a role in faster drug delivery in bipolar disorder and depression, and helping the aged population in bettering themselves at spatial tasks. The more research that's done, the more we will be able to better understand this protein's role. What we do know for certain is that CREB has more roles than we thought, making it seem more than a one dimensional protein involved simply in learning. 



References: 

http://blogs.scientificamerican.com/observations/why-do-antidepressants-take-so-long-to-work/
Image: http://www.nature.com/scientificamerican/journal/v301/n2/images/scientificamerican0809-70-I1.jpg