Blog 6: Ayhan et al (2011) and Burrows et al (2015)

Ayhan et al (2011) and Burrows et al (2015) examine different aspects of behavioral phenotypes typically seen in schizophrenia using transgenic and knockout mice models. Ayhan et al was an interesting read in terms of the gender-specific (and sometimes gender-non-specific) effects that were found throughout the experiment. For example, the noted effects of hDISC1 on immobility in the FST and TST were only significant in females while the effects of MK-801 and amphetamine (i.e. greater total locomotor activity) were only significant in males. I would have liked to see a comprehensive comparison and delineation of this gender-based data much like Table 1 to round out the article. This could be especially helpful for future experiments that examine the specifics of the temporal onset of schizophrenia, since it is widely known that human females generally display symptoms roughly 3-5 years later than males. To the authors’ credit, they acknowledge in the discussion that further experiments are certainly needed to look at gender differences in more detail, despite the data appearing to show gender associations between DISC1 and cognitive functions and disease frequency. 

For Burrows et al (2015), the primary question I had from their setup was the significance of using prepulse inhibition (PPI) and showing that environmental enrichment ameliorated the effects of it in the mGlu5 knockout group. My best attempt at understanding was that PPI involves delivering a ‘quieter’ stimulus before a startle pulse and the authors expected to induce an increased startle response in the animals injected with MK-801 compared to saline. However, how does the setup of the pulse trials and especially the variable intervals at which they were delivered fit into its function and purpose? The discussion briefly mentions how this finding could draw a parallel between the therapeutic effects of an enriched environment and pharmacological treatment. I can see where this comparison comes from in the data of Figure 5a, but I am still not fully grasping how PPI itself could be translated to a clinical model. Although a more comprehensive understanding of that protocol would give me a greater sense of confidence in this treatment recommendation, I still appreciate how the paper highlights a mix of genetic and environmental effects on schizophrenia to ensure that both are recognized as contributors to the development of this complex disorder.