Students Examine Brain Degeneration Caused by Alzheimer’s
About 4 million people in the United States have been diagnosed with Alzheimer’s disease. Nearly half of all people 85 and older are thought to have some form of dementia, according to PASSAGES Adult Resource Center fact sheets. So it’s no surprise that these kinds of degenerative diseases are the subject of intense scientific scrutiny, including research by students here at CSU, Chico.
Jonathan Day, Biological Sciences, has received $90,000 from the National Institutes of Health (NIH) to work with six students on a project involving pharmacological intervention for age-related neurodegeneration, which is related to diseases like Alzheimer’s and Parkinson’s.
“When neurons die,” Day explained, “the brain tries to compensate by forming new connections between the nerve cells, a process called synaptogenesis, the formation of new synapses. It goes on all the time in the brain, both with disease and without disease, and it seems to be a part of things like learning and memory.”
He and his students hypothesized that accelerating synaptogenesis would retard the progression of the neuron degeneration. They are looking closely at the cells and circuits in the brain that are affected by Alzheimer’s disease to test this hypothesis.
“The same thing probably happens in Parkinson’s disease and Huntington’s disease and any of the other neural degenerative diseases,” said Day. “There’s over 3,000 genetic degenerative diseases alone. We just happen to be working on those cells affected by Alzheimer’s.”
Working with neurons from embryonic mice and rats, Day’s students looked specifically at a process called phosphorylation, the way proteins within cells are modified by enzymes such as kinases and phosphatases. They first replicated work done by others, verifying that stimulating phosphorylation in certain nerve cells increases the number of synapses.
Then they took the project a step further, said Day. “We thought, ‘If we can increase phosphorylation by stimulating this pathway, perhaps we can stimulate it even more by inhibiting the pathway that results in dephosphorylation of the proteins in the cell.’”
They tested Cyclosporine A, a drug used as an immunosuppressant for cancer treatment that inhibits an enzyme in the brain that removes phosphate groups from specific proteins involved in synaptogenesis. They thought the drug would enhance phosphorylation of the proteins in the cell, perhaps ultimately leading to increased synaptogenesis.
The students used fluorescence microscopy to take picture of the proteins as synapses develop and used computer-assisted image analysis to quantify the changes. They found, as predicted, that the drug significantly increased the ability of a cell to change and form new neural connections. The undergraduate who spearheaded the research, Adam Ferris, presented two posters at the annual meetings of the Society for Neuroscience in Atlanta (2006) and San Diego (2007).
But exciting and encouraging results don’t mean immediate real-world applications, said Day, who is working on publishing the data and getting a grant to expand the project. “When the data are published, other researchers will read it and decide whether it might be useful. Whether this idea will ever get to clinical trials really depends on how many other scientists come up with similar ideas.”
It’s a slow process from a beginning research project through the hundreds of steps and protocols that culminate in clinical drug trials, said Day. “Ten or fifteen years from now, it might turn into some sort of clinical intervention. These things take a lot of time, money, and trained scientists. Most of the benefits we are reaping now in the biomedical sector, treating diseases, come from basic research questions of five to fifteen years ago. This is something that is unfortunately common because of the reticence that the general population—undergraduate students included—has towards math and science in general, taking as little of it a possible.”
Day is doing his best to overcome this reticence. He was one of the CSU, Chico 2008 Professional Achievement Honors winners for his work with students on these kinds of research projects, which “train potential scientists in how to do research,” he said.
CSU, Chico provides a unique opportunity for research and teaching, said Day, who was previously at Penn State as an assistant neurogerontology professor, senior research associate at the Andrus Gerontology Center at USC, and an NIH postdoctoral fellow in the Laboratory for Neuroendocrinology at the UCLA Geffen School of Medicine.
“At major research institutions, often teaching isn’t very highly regarded,” he said. “Undergraduate schools, for the most part don’t really target that kind of research-based scientific experience for their students. There is a nice balance at Chico State.”
—Anna Harris, Public Affairs and Publications