Ayhan and Burrow

These articles both dealt with modeling schizophrenia in rodents, which is an interesting change from the other anxiety and depression related articles we have read this semester. After reading the beginnings of the articles I was immediately intrigued in how the disease would be modeled and measured since symptoms of schizophrenia in humans include hallucinations, delusions, and other signs of being out of touch with reality which are difficult to measure in rodents. The first article, Burrow et al (2015) aimed to study the glutamatergic signaling related to schizophrenia and how environmental conditions effect it. Although this paper was more technically specific, I had trouble believing their model, that the mGlu5 knockout mice suffice as an adequate model of schizophrenia. This model is built off the understanding that NMDA and GLU receptor malfunctions are involved in schizophrenia. As we are learning even from these very studies, schizophrenia is a complex disease that we do not fully understand, so simply knocking out one type of glutamate receptor in rodents does not seem like a good representation of the disease. However, I do understand the Catch 22 at play here – how can you model a disease of which you don’t know all of the causes? I am not familiar with schizophrenia well enough to propose a thorough solution, but I was more easily convinced of the schizophrenia model in the other paper, Ayhan 2011. The Ayhan paper (2011) focused on the manipulation of the human Disrupted-In-Schizophrenia-1 (hDISC-1) gene, a gene known to be linked to schizophrenia, mood disorders, and brain development. I found this paper the most fascinating because it explored effects in both male and female mice pre- and post-natally. The sex and age/state of development of subjects in a study are always the variable that I am most interested in, so I was excited to see these important aspects included in the study. The data differed slightly between male and female groups, with females exhibiting fewer locomotor effects and greater effects in the DA levels in the hippocampus. Although this data may not mean anything conclusively to us now, because it is now known that these sex differences in schizophrenia exist, future researchers may look more directly into this correlation to uncover more about the disease and how it relates to sex. How do estrogen and testosterone levels affect the development of schizophrenia? How does the schizophrenic phenotype of male and female rodents compare pre and post adolescently? We do not even know if many of the sex differences we see in male and female human neurobiology are due to nature, nurture, or both, so studies like this can shed light on the topic even if just in animal models. This study highlights how important it is that neuroscience studies use both male and female subjects. I also enjoyed this paper because experimented with how prenatal conditions contribute to the diagnosis of schizophrenia of the child later on. Ayhan et al aimed to test if rodents can be predisposed to schizophrenia from genetic mutations in the womb, relating to the fact that recent research has linked influenza during pregnancy to schizophrenia in the child later in life. Out of all the topics I’ve been introduced to through my major, I am most fascinated by developmental neuroscience and women’s health/obstetrics. I understand that prenatal conditions are extremely important and influential to a child’s health and can trigger genes or cause mutations that will affect them their entire life. There is a lot we haven’t explored relating to how prenatal and birthing conditions affect the life of the offspring, and I believe there is a lot to uncover, but I appreciated how this paper explored the topic because it is something few studies attempt.