Seeking Balance in the Brain: UCSF, February 2011

Some signals in the brain inhibit action, and some spark or excite it. A balance of those two impulses is critical to healthy brain function – and an imbalance lies beneath many of the most common brain problems such as epilepsy, Parkinson’s disease and traumatic injuries.

Researchers Arturo Alvarez-Buylla, PhD, and John Rubenstein, MD, PhD, who discovered and characterized the cells responsible for the inhibitory signals in the cerebral cortex of the brain, continue to build on that seminal work. They are now teaming up with Scott Baraban, PhD, professor of neurological surgery, and Arnold Kriegstein, MD, PhD, professor of neurology and director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

The four investigators meet regularly and share students, postdoctoral fellows and technicians, which keeps information flowing among the labs

“These would be difficult things to do as an individual lab,” Baraban says. “To me, it’s a huge advantage to have all that expertise.”

Under grants from the California Institute for Regenerative Medicine and the National Institutes of Health, the researchers are implanting stem cells to give a boost to ailing brains in animal models of human disease – slowing or stopping seizures in epilepsy, for instance, or increasing agility in animals with Parkinson’s disease.

Patients with those diseases suffer from an imbalance between their inhibitory and excitatory signals in specific regions of the brain. The researchers tried implanting embryonic inhibitory neurons into mouse brains, and found they could restore some of the inhibitory and excitatory balance. The early work showed great strides in epilepsy; Kriegstein joined the project with an interest in broadening it to Parkinson’s and other diseases, and the work showed further promise.

“In Parkinson’s, when dopamine neurons die, certain pathways become overactive,” Kriegstein says. “We put our neurons into the part of the brain called the striatum, and the new cells received excitatory synapses.”

That means, Kriegstein says, that the animal brains had the right tools at the right time. The new cells worked just as if the animals had been born with the transplanted cells. “You couldn’t produce the timing of the inhibitory signals in any other way,” he says.

It’s still proving tricky to move from undifferentiated human stem cells to the particular type of nerve cell that’s needed, Kriegstein says, and work continues.

“With that piece of the puzzle – a human cell line that might work – we’ll be getting closer to a clinical trial,” he says.


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