Annotated Bibliography

De la Rosa, A., Solana, E., Corpas, R. et al. Long-term exercise training improves memory in middle-aged men and modulates peripheral levels of BDNF and Cathepsin B. Sci Rep 9, 3337 (2019). https://doi.org/10.1038/s41598-019-40040-8

The authors of this paper are from the Freshage Research Group from the Department of Physiology at the University of Valencia and CIBERFES. This randomized controlled trial to determine if long-term exercise training promotes memory maintenance in middle-aged men by changes in neurotrophic factors and lipid oxidation markers in blood samples. This study includes eighty-six healthy men between 17 and 68 years old and concluded that long term exercise-training improves memory performance in male middle-aged rugby players and decreases peripheral resting levels of the neurotrophins BDNF and CTSB. The main limitation of this study is that it did not include women. This paper is interesting to my research question because it examines the usage of exercise as a preventive strategy for neurodegeneration diseases in which memory loss is the hallmark symptom.

Maass, A., Düzel, S., Brigadski, T., Goerke, M., Becke, A., Sobieray, U., Neumann, K., Lövdén, M., Lindenberger, U., Bäckman, L., Braun-Dullaeus, R., Ahrens, D., Heinze, H. J., Müller, N. G., Lessmann, V., Sendtner, M., & Düzel, E. (2016). Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults. NeuroImage, 131, 142–154. https://doi.org/10.1016/j.neuroimage.2015.10.084

The last author, Düzel, is associated with the Otto-von-Guericke University in Germany and the authors have no declared conflict of interest. This paper outlines a randomized controlled trial with the goal of finding the relationships of peripheral IGF-1, VEGF, and BDNP levels to exercise-related changes in memory and the hippocampus in older adults. This was a small study with forty healthy older adults that participated in a 3-month aerobic exercise study. The control group engaged in progressive muscle relaxation/stretching and the experimental group did aerobic physical exercise. Within this study, they conducted assessments of fitness levels, growth factor and cortisol levels, cognitive measures, and high-resolution MRI. For my particular research, I was interested to learn about the BDNP levels. The authors’ concluded that in this 3-month intervention there was a significantly increased fitness level but no effect on BDNF levels in the blood. The authors’ acknowledged the limited scope of the study. This paper provided citations that aided me in continuing my research and some behavioral analysis of the effect of exercise in healthy older adults.

Mahalakshmi, B., Maurya, N., Lee, S. D., & Bharath Kumar, V. (2020). Possible Neuroprotective Mechanisms of Physical Exercise in Neurodegeneration. International journal of molecular sciences, 21(16), 5895. https://doi.org/10.3390/ijms21165895

The last author of the paper, Bharath Kumar, is from the Department of Medical Laboratory Science and Biotechnology at Asia University. There are no notes of conflicts of interest or external funding that demonstrate concern for potential strong biases. This review article outlines the possible neuroprotective mechanism of physical exercise in neurodegeneration through the review of previous studies. Physical exercise (PE) has neurological benefits but should not be the primary treatment for neurodegenerative diseases. PE improves the production of neurotrophic factors, hormones, and neurotransmitters. This review article overviews the neuroendocrine and neurotransmitter regulation, neural insulin signaling, BDNF-signaling, irisin production and secretion, anti-neural-inflammatory and anti-neural-oxidative, and various other effects of PE. This review article provides me with an outline of all the possible approaches I can make in my research of the neuroprotective mechanisms. Based on the brief descriptions I want to further explore the role of irisin in the beneficial effects of exercise on the brain.

Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., Lin, J. D., Greenberg, M. E., & Spiegelman, B. M. (2013). Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell metabolism, 18(5), 649–659. https://doi.org/10.1016/j.cmet.2013.09.008

The authors of this paper are from Harvard Medical School and the University of Michigan Medical Center. This paper is a randomized controlled trial showing that FNDC5 is induced in exercise and is cleaved and secreted as irisin in the hippocampus of mice. The paper analyzes hippocampal FNDC5 gene expression using C57/B16 wild-type mice under exercise conditions and sedentary conditions. Figure 1 provides graphical proof of increased FNDC5 gene expression in the hippocampus in comparison to other parts of the brain. Further experiments are outlined to create a model of the pathways activated in the hippocampus by endurance exercise. The proposed pathway is that exercise leads to the increased transcription of PGC-1ɑ which induces FDNC5 gene expression that leads to increased levels of BDNF. This paper provided the proposed pathway of exercise’s effect on BDNF but does not answer how does the PGC-1α/FNDC5/BDNF pathway gets initiated in exercise? This paper provided mechanistic knowledge needed for my research in the hippocampus which is largely affected in neurodegenerative disorders.

Young, M. F., Valaris, S., & Wrann, C. D. (2019). A role for FNDC5/Irisin in the beneficial effects of exercise on the brain and in neurodegenerative diseases. Progress in cardiovascular diseases, 62(2), 172–178. https://doi.org/10.1016/j.pcad.2019.02.007

The last author of the paper Christiane D. Wrann is involved in Massachusetts General Hospital and Harvard Medical School along with the Broad Institute of MIT and Harvard, Harvard Stem Cell Institue, and the Henry and Allison McCance Center for Brain Health. There is a statement of a conflict of interest due to Christiane D. Wrann’s holding of a US Patent application. I do not believe this invalidates any research presented and this resource remains useful in my research. This review article analyzes the possible underlying mechanism for the beneficial effects of exercise on the brain is the brain-derived neurotrophic factor (BDNF), FNDC5, and Irisin. BDNF has been shown to be a crucial regulator of the beneficial effects of exercise in the brain and regulates synaptic plasticity and cognitive function. The FNDC5 protein produces Irisin. More research is needed to determine the full effect of FNDC5 and Irisin on cognitive function. This review article provides more background information on the mechanism of FNDC5 and Irisin that will be helpful in my exploration of the subtopic of Irisin in my research. Based on this background knowledge I want to locate primary research on this topic.