YOKOHAMA CITY UNIVERSITY

YCU Science Summer Program 2013

The fusion of different disciplines of life, material and medical sciences creates the innovative prospects

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Third Day—August 21 (Wednesday)

Lecture No. 5 — “Neurobiology of Alzheimer's diseases - How can we enjoy green old age?”

Yoshio Goshima, Professor and Director of the Graduate School of Medicine

 Professor Yoshio Goshima spoke to the students about the appeal of medical research in an animated fashion and gave an ardent call to join young people around the world in pursuing the many unknown puzzles in medicine.

 In this summer program lecture, we will look at new mechanisms behind dementia, and particularly Alzheimer’s disease, which is an enormous health concern the world is grappling with right now. Alzheimer’s disease is already a major problem in the United States and Europe, and its incidence has skyrocketed in recent years in China, South Korea, Indonesia, Singapore, and other Asian countries, where it is becoming a serious health issue. For example, the social cost caused by the disease is estimated to be over 50 billion dollars worldwide, 20 billion dollars in the United States, and 10 billion dollars in Japan (about a trillion yen). This estimate illustrates the extent of the disease and just how important it is to overcome the disease on a global level.

 The discoveries and findings we will look at today are the fruits born from a chance that presented itself in an encounter between a research topic our research group has been focused on, namely how do complex neural circuits form, and the pathological laboratory initiatives of Professor Yasuo Ihara (University of Tokyo and currently professor at Doshisha University), who was studying how to characterize the onset of Alzheimer’s disease. I will try to give a simple explanation of these discoveries and findings.

 Before I begin, I’d like to briefly describe our efforts so far in tackling the problem of how neural circuits form. A neural circuit is formed when a neurite grows and creates a synapse, a structure for passing signals, with another particular cell. If this process does not go well, the neural circuit will not function properly. The problem is that if neurons propagate randomly in the central nervous system, consisting of the brain and spinal cord, the circuits will short out, which is believed to cause epilepsy and similar disorders. We know that there is a large quantity of material in the central nervous system that inhibits the growth of neurons to prevent these short circuits. The existence of this material is thought to be the reason why nerves don’t regenerate after a spinal cord injury and permanently lose their function for the most part. A protein called the collapsin response mediator protein (CRMP) was discovered to be the molecule that controls the growth of neurites.

 At the same time, Professor Ihara’s group, which was working on Alzheimer’s research, found that neurons in the brain tissue of Alzheimer’s patients accumulate a large amount of CRMP that has undergone phosphorylation (phosphorylated CRMP). However, the group had no idea how this phosphorylation was connected to the onset of the disease. To shine a light on this problem, we produced genetically modified mice (nonphosphorylated knock-in mice) in which CRMP phosphorylation did not occur. We then studied how the cognitive decline action, which is marked by -amyloid, a protein that is a causative agent in Alzheimer’s disease, changed in the knock-in mice. Our research demonstrated that in normal wild mice, the administration of -amyloid in the brain triggered a decline in cognitive functioning. But in the knock-in mice, absolutely no decline in cognitive functioning was seen after the administration of -amyloid.

 This finding suggests that the phosphorylation of CRMP is involved in the onset of the pathology of Alzheimer’s disease. To determine if this mechanism applies to humans will require much more research. Nevertheless, through the progress of this research, the day may come when a novel treatment is established to save millions of patients from Alzheimer’s disease.

 Why not join us in taking on difficult challenges like these

Lecture No. 6 — “The stem cells of normal and cancer tissues in solid organs and their relations”

Yun-Wen Zheng, Assistant Professor, Department of Regenerative Medicine, Graduate School of Medicine

 Dr. Yun-Wen Zheng, whose research is making use of regenerative techniques to cure diseases, gave an extremely interesting explanation of the relationship among cancer cells, stem cells, and iPS cells, a key word in modern medical science.

Practical Class No. 4 — Tour of Facilities at the Advanced Medical Research Center

 Students toured the Advanced Medical Research Center, which was completed in December 2012, where they viewed demonstrations of mass spectrometry, cell culture, cell preservation, and other operations, talked with researchers, and got a feel for cutting-edge medical research.

Hisashi Hirano, Professor, Graduate School of Nanobioscience and Director of the Advanced Medical Research Center

 Director Hisashi Hirano, a global leader in proteomics research (a large-scale research study of the entire set of proteins in humans that is used in elucidating life sciences), described a mass spectrometer, which provides valuable information for diagnoses and disease discovery.

Yun-Wen Zheng, Assistant Professor, Department of Regenerative Medicine, Graduate School of Medicine

 Assistant Professor Zheng explained in detail how the university preserves its precious human cells, the research findings being discovered from cell cultures, and the equipment used for the research.

Wrap-Up

 Looking back on the program, the SSP Supervisor added a few words to provide a unified picture of the day’s lectures and the research being done at the Advanced Medical Research Center, an affiliated facility of the university. The students, who seemed to struggle with the material at first, came to see the importance of uniting techniques from different disciplines in order to make rapid developments in science and medicine. The students had a lively exchange of opinions and impressions.