Young brains are plastic, meaning their circuitry can be easily rewired to promote learning. By adulthood, however, the brain has lost much of its plasticity and can no longer readily recover lost function after, say, a stroke. Now scientists have successfully restored full youthful plasticity in adult mice by transplanting young neurons into their brain—curing their severe visual impairments in the process.
In a groundbreaking study published in May in Neuron, a team of neuroscientists led by Sunil Gandhi of the University of California, Irvine, transplanted embryonic mouse stem cells into the brains of other mice. The cells were primed to become inhibitory neurons, which tamp down brain activity. Prior to this study, “it was widely doubted that the adult brain would allow these cells to disperse, integrate and reactivate plasticity,” says Melissa Davis, first author of the study. Scientists have been attempting such a feat for years, refining their methods along the way, and the Irvine team finally saw success: the cells were integrated in the brain and caused large-scale rewiring, restoring the high-level plasticity of early development. In visually impaired mice, the transplant allowed for the restoration of normal vision, as demonstrated by tests of visual nerve signals and a swimming maze test.
The scientists have not yet tested the transplanting technique for other neurological disorders, but they believe the technique has potential for many conditions and injuries depending on how, exactly, the new neurons restore plasticity. It is not yet known whether the proliferation of the transplanted cells accounts for the restored plasticity or if the new cells trigger plasticity in existing neurons. If the latter, the treatment could spur the rewiring and healing of the brain following traumatic brain injury or stroke.
The team used inhibitory neurons because they showed the most promise in earlier experiments. But that specific type of neuron also has particular clinical promise because many psychiatric and neurological disorders involve an imbalance between excitation and inhibition, including epilepsy, schizophrenia and chronic pain. Several laboratories, including one led by Stewart Anderson of the University of Pennsylvania Perelman School of Medicine, have demonstrated that transplanting inhibitory neurons from healthy mice has improved symptoms in mice with models of those diseases. The new method would allow for more widespread brain changes, potentially eradicating the disease entirely. For people who have not been helped by medications, “a heroic treatment such as neuron transplantation could be potentially life changing,” Anderson says.
Many obstacles remain before neuron transplantation happens in humans. First, mouse stem cells may not be effective or safe for transplantation into humans, and scientists do not yet know how to coax human stem cells into becoming the type of precursor neurons needed for the procedure. In addition, transplanted cells take more than a month to mature in the recipient mouse brain; human cells would in theory take considerably longer, perhaps years.
Despite these hurdles, experts are excited about the breakthrough. They believe neuron transplantation may someday provide a cell-based therapy to effectively and, more important, permanently treat age-related and developmental diseases.