Sunday, March 19, 2017

Week 7

I found both of this weeks papers to be extremely interesting. First, addressing just the actual animal models of schizophrenia used, I think the one that Ayhan et al. had to be the most convincing, and my favorite, so far. The DISC1 gene is so complex and its expression during different points in development result in different behaviors, making its disruption a great way to model schizophrenia. Schizophrenia is a disease that is so dependent on development, that its important to research the process in order to find those that are genetically predisposed before they start showing symptoms. Knowing the changes of expression of the DISC1 gene over development could make it possible to even prevent the manifestation of schizophrenia if we can stop the abnormal expression before it starts as it commonly does in young adulthood. The model from the Burrows et al. paper was great for testing a few specific symptoms of schizophrenia (like reduced PPI, long-term memory deficits, and spontaneous locomotor activity) but as a holistic model of the disease, it is not ideal.

One thing I liked about the Ayhan et al. paper was that they really focused on how the model could be used for future studies. They kind of just found out a ton of information about the mutant hDISC1 gene and expression over time and its behavioral and anatomical effects. They developed this model that mimics the disorder of schizophrenia so well and set up other scientists so that they can generate new experimental groups of mice based on the phases of postnatal life, including sexual maturation and adulthood. Learning more about these pivotal stages in development in regards to the mutant gene will give us the ability to regulate when and how the protein should be expressed. This model will also be helpful in greater exploration of the sex differences seen in expression.

For the Burrows et al. paper, I got really excited when I saw it was using environmental enrichment. Though I don't think EE is the cure all to any specific disease, it has undeniable benefits in regards to basic cognitive functioning. A few years ago, I wrote a paper and did a lot of research regarding EE and Alzheimer's disease, and EE helped to slow down the progression of AD in animal models. I think that as science-minded people, we sometimes forget to take a step back from the drugs and circuits and neurotransmitters and not realize that there is a possibility to train our brain from the outside-in. As seen in these KO mice, EE restores normal functioning of the abnormal behaviors, except for the short-term memory test, the Y-maze. However, I question the validity of a locomotor based short-term memory test, because as we saw in Figure 1, the mice in the EE has decreased overall locomotor activity. In the Y-maze, the KOEE group did not restore the normal behavior but had decreased distance covered in the maze, potentially due to the EE itself and not its effect on STM.

Though EE does have its benefits, the real challenge would be translating the idea of an EE into a therapeutic method that would work for humans, and most likely using it along with drug therapy.

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