Researchers led by a team of students and faculty at the University of Idaho discovered how adult brains may be able to more easily create new neural connections, potentially providing insight for treating neurological diseases and injuries.
To do this, scientists from three universities analyzed how certain genes in adult mice prevent and foster the creation of synaptic connections, or the brain’s communication pathways between neurons, said Peter Fuerst, research team lead and UI associate professor of biology.
“We combined different mouse genetic backgrounds and we added a drug to deactivate certain genes,” he said. “When we deactivated those genes, we saw that the neurons were able to make new connections, showing that the genes themselves (and) their protein products, were preventing new connections from being made.”
The study was published Nov. 7 in the Journal Proceedings of the National Academy of Sciences and is titled “DSCAM-Mediated Control of Dendritic and Axonal Arbor Outgrowth Enforces Tiling and Inhibits Synaptic Plasticity,” according to a UI news release.
Similar to a mouse’s gene preventing the formation of new connections, as humans get older, Fuerst said it becomes more difficult to make new neural connections because the neural system is stabilizing, which is when it is done creating a large amount of connections.
This becomes problematic for people with injuries and diseases affecting the central nervous system, he said, because it prevents the brain from recovering and repairing through forming neural connections.
“In a person with autism you might not know what exactly is going on, but you might know this person has a mutation in this gene,” Fuerst said. “We can go in and use mice to figure out specifically what’s happening in the nervous system to try to help the person communicate better or whatnot, based on the mice. So, sort of basic research building to translational research.”
The discoveries made in the mouse model study may allow for scientists to identify signaling pathways in the human brain and use drugs that target those pathways to combat neurological diseases, or to foster growth in injured brains, Fuerst said.
Drugs like this already exist, he said, and are sometimes used in cancer therapy.
Another researcher involved in the project, assistant professor at the University of Louisville School of Medicine Bart Borghuis, said they are currently developing a list of drugs they believe are worth testing for performance relative to completely removing a gene they identified as responsible for inhibiting change in the brain’s synapses, or synaptic plasticity: the down syndrome cell-adhesion molecule, or Dscam.
“In a human right now, it’s not feasible to just manipulate genes freely. You certainly just don’t want to knock something out,” Borghuis said. “Fortunate thing is, we have quite a bit of knowledge about the signaling pathways… There are a couple of candidates that we think are important downstream signaling molecules of the Dscam. And for those, we can make use of available pharmacological agents, or drugs, that can simply block, or inhibit, some of those Dscam protein targets.”
The research was funded by a $400,000, two-year grant from the National Institute of Health (NIH), and their plan is to turn it into a 5-year NIH project. Borghuis said they are planning their next experiment and are considering looking at more genes and signaling pathways.
“When you start a project like this, you rarely start it because you have one question,” he said.
Kyle Pfannenstiel can be reached at firstname.lastname@example.org or on Twitter @pfannyyy