Friday, 8 February 2013

Scientists reveal the role of SFRP3 to antidepressant response

In two separate studies involving both mouse and humans, researchers from the John Hopkins University have discovered how antidepressants and electroconvulsive therapy activate brain stem cells, which in turn relieve depression symptoms by developing into new neural cells. The studies have implications in two fields, creating new genetic tests that will predict an individuals response to antidepressant therapy and in the development of new treatments for depression.

According to Hongjun Song, chief author in both studies, previous published literature suggests that antidepressants and electroconvulsive therapies both induce adult neural stem cells to create new neurons. However they all fail to describe the deeper molecule mechanisms involved in this process, and this is where their studies are focused.

Song and his team first experimented on a mouse model, on two different groups of mice. One was treated with electroconvulsive therapy and one wasn't (control group). The comparison between the two groups showed significant differences in the expression of the sFRP3 gene. SFRP3 regulates the production of a protein, that its presence inhibits neural stem cell activity.

"sFRP3 inhibits maturation, dendritic development, and spinal formation of new neurons",  highlight taken from the study.

Image of neurons
Mouse neurons

The researchers then conducted a second experiment, again on mouse. This time the first group was comprised of healthy mice and the second of genetically engineered ones that lacked the sFRP3 protein. Both were given antidepressant drugs and both groups responded similarly showing no behavioural changes. This strongly indicates that antidepressant treatments work by blocking the function of the sFRP3 protein, in its absence there is simply nothing left to block.

The last step was to confirm the findings on a human model. The researchers analysed genetic data from 541 patients with depression and recorded how they responded to antidepressant therapy. They discovered the existence of three sFRP3 gene variations that tended to respond better to the treatment. All three of these variations were linked to reduced gene expression, which again strongly suggests that sFRP3 inhibits neural stem cell activity.

According to Song, the gene seems to be easily affected by many conditions and other factors as well, for instance exercise.

"FRP3 seems to be a gatekeeper that links activity to new neuron growth", he concludes.

Depression is a state of low mood and aversion to activity that can have a negative effect on a person's thoughts, behaviour, feelings, world view, and physical well-being. Some common symptoms include:
  • Agitation, restlessness, and irritability
  • Becoming isolated
  • Finding it difficult to concentrate
  • Dramatic changes in appetite, often with associated with weight gain or loss
  • Fatigue 
  • Feelings of hopelessness and helplessness
  • Feelings of worthlessness, guilt and even self-hate
  • Losing interest in activities that were once pleasurable
  • Suicidal tendencies
  • Sleeping too much or too little

Informational video on Depression

Jang, M., Bonaguidi, M., Kitabatake, Y., Sun, J., Song, J., Kang, E., Jun, H., Zhong, C., Su, Y., Guo, J., Wang, M., Sailor, K., Kim, J., Gao, Y., Christian, K., Ming, G., & Song, H. (2013). Secreted Frizzled-Related Protein 3 Regulates Activity-Dependent Adult Hippocampal Neurogenesis Cell Stem Cell, 12 (2), 215-223 DOI: 10.1016/j.stem.2012.11.021
Jang, M., Kitabatake, Y., Kang, E., Jun, H., Pletnikov, M., Christian, K., Hen, R., Lucae, S., Binder, E., Song, H., & Ming, G. (2012). Secreted frizzled-related protein 3 (sFRP3) regulates antidepressant responses in mice and humans Molecular Psychiatry DOI: 10.1038/mp.2012.158

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