Learning from Obstacles in Science

The Western diet is high in fats and sugar and can lead to an increase in metabolic diseases, which cause a chronic state of peripheral inflammation (1). My project this summer aims to observe the effect of diet on brain inflammation. We used a mouse model of tagged peripheral monocytes (3). Monocytes turn into macrophages, which target inflammation in the body and brain (2). These mice were fed either a diet high in fat and fructose or a normal diet for 5 weeks. Then the blood from their brain was washed out, and the brain was sliced. The slices were stained for the genetic tag for the peripheral macrophages. Peripheral macrophages found in the brain suggest that chronic inflammation weakens the blood-brain barrier, allowing peripheral macrophages to cross where they increase brain inflammation. This may cause damage and may have links to diseases such as Alzheimer’s Disease and Parkinson’s Disease, which show increased inflammation in the brain (4). This project would further support the idea that a healthy diet could be a key factor in prevention of brain diseases.

This project, as well as science in general, had many obstacles that I had to overcome. Originally, I planned to analyze a different genetic mouse that modeled Alzheimer’s disease. Those mice were also going to be fed a high fat high fructose or control diet, and were going to be compared to see if there was an increase in peripheral macrophages in the brain in diet treated mice. However, those brains didn’t have the blood cleared from the brain, which limited our ability to see the stain. To overcome that problem, we used the new mouse type that had peripheral monocytes tagged, which had the blood removed from it. With this new mouse model, I would have a smaller number of animals, but I could better test my hypothesis.

I enjoy the day-to-day life in research. I was expecting it to be somewhat repetitive, but that was far from the case. I had many problems that I had to solve and was constantly learning, which made the time fly by. My day was broken up by working on different parts of my experiment, writing and reading literature, and meeting and talking with my lab members. The best part for me was that I constantly learned new things. There were many hiccups in my summer experience, which were disheartening at times. However, solving these problems and further learning more made it rewarding as well. The Tansey lab has many members who have been very helpful in solving these problems. I enjoyed being a part of a larger team, as there were so many projects going on that I could learn from.

References

  1. De Sousa Rodrigues, M. E., Bekhbat, M., Houser, M., Chang, J., Walker, D., Jones, D. P., Oller do Nascimento,C., Barnum, C. J. & Tansey, M. Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice. Brain, Behavior, and Immunity 59: 158-172, 2017.
  2. Khoury, J. E., Toft, M., Hickman, S.E., Means, T. K., Terada, K., Geula, G., & Luster, A. D. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nature Medicine 13: 432-438, 2007.
  3. Saederup, N., Cardona, A. E., Croft, K., Mizutani, M., Cotleur, A. C., Tsou, C.-L., Ransohoff, R. M., & Charo, I. F. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice. PLoS ONE 5: e13693, 2010.
  4. Selkoe, D. J. The therapeutics of Alzheimer’s disease: where we stand and where we are heading. Annals of Neurology 74: 328-336, 2013.
Lindsey Sniffen is a senior majoring in Neuroscience and Behavioral Biology at Emory University in Atlanta, GA. She is a 2017 Integrative Organismal Systems Physiology (IOSP) Fellow in Dr. Malu Tansey in the Department of Physiology at Emory University in Atlanta, GA. Her fellowship is funded by the APS and a grant from the National Science Foundation Integrative Organismal Systems (IOS) (Grant #IOS-1238831). After graduation, she plans to pursue a Ph.D. in pharmacology, and then work in the pharmaceutical industry.

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