November 06, 2008
Gene Silencing Boosts Neuron Growth For Repair

By silencing genes that inhibit neural growth some scientists think they can create neurons that repair brain and spinal damage.

Boston, MA—Silencing natural growth inhibitors may make it possible to regenerate nerves damaged by brain or spinal cord injury, finds a study from Children's Hospital Boston. In a mouse study published in the November 7 issue of Science, researchers temporarily silenced genes that prevent mature neurons from regenerating, and caused them to recover and re-grow vigorously after damage.

Because injured neurons cannot regenerate, there is currently no treatment for spinal cord or brain injury, says Zhigang He, PhD, Associate Professor of Neurology at Children's and senior author on the paper. Previous studies that looked at removing inhibitory molecules from the neurons' environment, including some from He's own lab, have found only modest effects on nerve recovery. But now He's team, in collaboration with Mustafa Sahin, MD, PhD, Assistant Professor of Neurology at Children's, demonstrates that re-growth is primarily regulated from within the cells themselves.

"We knew that on completion of development, cells stop growing due to genetic mechanisms that prevent overgrowth," explains He. "We thought that this kind of mechanism might also prevent regeneration after injury."

Keep in mind that aging basically amounts to a slow accumulation of injury. The ability to make cells grow is also essential to the development of rejuvenation therapies. Brain rejuvenation is the hardest challenge for aging reversal therapies. So the development of techniques for turning on neuron growth has special importance.

By blocking inhibiting genes that suppress the mTOR pathway the scienists were able to boost brain repair in injured mice.

The key pathway for controlling cell growth in neurons, known as the mTOR pathway, is active in cells during development, but is substantially down-regulated once neurons have matured. Moreover, upon injury, this pathway is almost completely silenced, presumably for the cell to conserve energy to survive. He and colleagues reasoned that preventing this down-regulation might allow regeneration to occur.

He and his team used genetic techniques to delete two key inhibitory regulators of the mTOR pathway, known as PTEN and TSC1, in the brain cells of mice. After two weeks, the mice were subjected to mechanical damage of the optic nerve. Two weeks post-injury, up to 50 percent of injured neurons in the mice with gene deletions of PTEN or TSC1 survived, compared to about 20 percent of those without the deletions. And of the surviving mutant mice, up to 10 percent showed significant re-growth of axons, the fiber-like projections of neurons that transmit signals, over long distances. This re-growth increased over time.

Share |      Randall Parker, 2008 November 06 11:07 PM  Biotech Neuron Repair


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