A ubiquitous signaling molecule, nitric oxide (NO), turns off the production of new neurons in the adult brain, researchers have discovered. By shutting down this off switch, doctors may one day be able to generate new neurons in the brains of patients suffering from neurological diseases or traumatic injury.
Most neurons in the human brain are born while the fetus is still tucked inside its mother's womb. But in recent years, researchers have discovered that adult brains have stem cells that develop into brand-new nerve cells later in life. Doctors are tantalized by this because many ailments associated with aging, such as Parkinson's or Alzheimer's disease, are caused by degeneration of neurons in the brain. If doctors could stimulate neuron development at will, it might be possible to slow or even reverse the damage caused by such diseases. Until now, however, researchers have made little progress in understanding what turns on adult neuron development.
So New York neuroscientists Grigori Enikolopov of the Cold Spring Harbor Laboratory and Steven Goldman of Cornell University decided to look instead for the off switch. They focused on an enzyme called neuronal nitric oxide synthase (nNOS), suspected to put the brakes on cell proliferation by producing NO. Using rats, the team injected a nNOS inhibitor into areas of the brain where new stem cells are known to divide. To their surprise, the number of stem cells that developed into neurons increased by 70%. "It was like we released the parking brake," said Enikolopov. A neuron-specific dye proved that the new stem cells had indeed become neurons.
Buoyed by this success, the team conducted studies in a strain of mice that don't produce nNOS. In these animals' brains, the number of dividing cells was 40% higher than in normal mice. And again, the dye showed that the new cells morphed into neurons. This is the first time a stem cell differentiation inhibitor has been identified in the brain, the team reports in the 5 August Proceedings of the National Academy of Sciences.
"The research results show a clear-cut regulatory relationship between nNOS and neurogenesis," says stem cell biologist Dennis Steindler of the University of Florida in Gainesville. "Nitric oxide has been so extensively studied for its other properties, it's amazing that no one has made this connection before. I love this paper."