Alzheimer’s has historically been a disease researchers have struggled to find an effective treatment or cure for — however, Stanford University Prof. Carla Shatz hopes to change that.
Shatz’s work at the forefront of Alzheimer’s research was featured Monday during the Bernard W. Agranoff Lecture, an annual talk honoring the neuroscience pioneer who retired from his teaching position at the University in 2003.
Shatz was the first woman to earn tenure in the basic sciences at Stanford, where she is currently a professor of biology and neurobiology. Her research focuses on synaptic plasticity, or the ability of the gaps between nerve cells to strengthen or weaken over time, in relation to Alzheimer’s disease.
Throughout her lecture, Shatz emphasized the importance of a type of gene — MHC class I — specifically the MHC gene PirB. Her research teams throughout the years have focused on studying the visual cortex in the brain to uncover whether that particular gene is involved in regulating synaptic plasticity.
The MHC family of genes is complex and because the team pinpointed the family as important in diseases like Alzheimer’s, there may be more need to focus on their specific functions.
Shatz focused heavily on what she called “critical periods,” during which learning occurs, in the mice she studied. She said the genes that enable this type of learning remain present in elderly people or those with Alzheimer’s, but are repressed.
Shatz also said her team found that the PirB gene inhibits the ability of synapses to strengthen and weaken over time in response to increases or decreases in their activity. This may in turn contribute to Alzheimer’s disease.
“PirB downstream signaling opposes cascades that are required for synaptic plasticity,” she said. “Especially, more interesting a question for me as I get older is: Is this enough? We know that there’s a co-regulation between synaptic weakening and synaptic pruning and the PirB loss of function.”
The goal, Shatz said, is to find a way to inhibit PirB in humans, which contributes the loss of synapses in a process called “pruning.”
“One of the ways we investigated this question was simply to take an Alzheimer mouse model and cross it with germline PirB knocked out mice and to ask whether in the absence of the PirB receptor, these mice might be protected from memory loss,” she said.
Employing basic memory tests, Shatz’s team found that when PirB receptors were blocked in mice that modeled Alzheimer’s, they performed on par with normal mice.
“What we discovered was in the absence of the PirB receptor they were performing memory discrimination at the same level as model-type mice,” she said.
Shatz ended her lecture on a hopeful note, saying the need for a pill to block PirB function could be on the forefront of her research. Though she said that kind of development takes time, the advances so far are promising.
Neuroscience post-baccalaureate student Sharena Rice said she learned a lot from Shatz’s lecture and was especially fascinated by the way in which she conducted her research by using the visual cortex as a method of discovering PirB functions.
“This opened my eyes to visual neuroplasticity,” Rice said. “It brings up more questions and we need questions to identify more answers.”