Stopping a receptor called 'nogo' opens ways to keep the brain sharp

Washington, Mar 19 : Want to keep your brain sharp? Well, then the new findings about a protein called the nogo receptor might be of great help.

Researchers at the University of Rochester Medical Center have found that reducing the nogo receptor in the brain leads to stronger brain signaling in mice, effectively boosting signal strength between the synapses - the connections between nerve cells in the brain.

The ability to boost such connections is essential to the brain's ability to rewire - a process that happens constantly as we learn and remember.

The study ties together several research threads that touch upon the health benefits of exercise. While those benefits are broadly recognized, how the gains accrue at a molecular level has been largely unknown.

The researchers found that reducing the effect of the nogo receptorould produce changes in the brain that likens those brought about by exercise.

"One of the central questions in neuroscience is - what is the molecular and cellular basis of learning? The nogo receptor seems to play a role," said Roman Giger, Ph.D., associate professor in the Department of Biomedical Genetics, who led the study.

The researchers found that in some areas of the brain, such as the hippocampus, the nogo receptor is at least 10 times more prevalent than in the spinal cord.

In the brain, the researchers found that the nogo receptor wields broad influence over a process known as neuroplasticity, which describes how our brain cells change and adapt constantly to meet our needs.

The researchers found that the nogo receptor plays an important role in changing the brain in two ways.

First, the molecule plays a completely unexpected role manipulating the strength of signals between brain cells in the synapses.

Led by Peter Shrager, Ph.D., professor of Neurobiology and Anatomy, the research team made sophisticated measurements of the strengths of the signals as they passed from cell to cell in mice.

They discovered that mutant mice with fewer nogo receptors than normal had stronger brain signalling, what scientists call 'long-term potentiation.'

It was found that the molecule also affected tiny structures known as dendritic spines, crucial connections that are extensions of the neuron and help cells 'talk' to other cells.

The researchers also found that mice with lots of the nogo receptor had a different mix of dendritic spines than normal mice. In the hippocampus, the mutant mice had fewer mushroom-shaped dendritic spines and more stubby and thin spines than the other mice.

Researchers said that they don't yet know the ramifications of the change, but it's firm evidence that the nogo receptor has effects on the anatomic structure of the brain. Creation and removal of dendritic spines is an important form of brain rewiring.

Shrager and his team attributes much of the effects of the nogo receptor to its ability to strongly bind to a growth factor known as FGF2 (fibroblast growth factor 2), which in the brain and other parts of the central nervous system nourishes neurons, allowing them to branch out and grow new sprouts.

When the nogo receptor is present in large quantity, it binds to FGF2 molecules, and as a result neurons no longer branch and sprout as they otherwise would.

Giger said that altogether, the findings show that the nogo receptor has a broad impact on processes in the brain that underlie learning and memory.

The findings are in the March 12 issue of the Journal of Neuroscience.

ANI