UCSF scientists have used a novel cell-based strategy to treat motor symptoms in rats with a disease designed to mimic Parkinson's disease.
The strategy suggests a promising approach, the scientists say, for treating symptoms of Parkinson's disease and other neurodegenerative diseases and disorders, including epilepsy.
The scientists transplanted embryonic neurons from fetal rats into an area of the adult rat brain known as the striatum, which integrates excitatory and inhibitory neurotransmitter signals to control movement. In Parkinson's disease, cells that produce the neurotransmitter dopamine are damaged, and thus unable to project their communication wires, or axons, to the region. As a result, the balance of excitation and inhibition in the striatum is lost, causing the motor deficits that are a primary symptom of the disease.
In the study, the transplanted embryonic neurons migrated and integrated into the correct neural circuitry of the striatum, matured into so-called GABAergic inhibitory interneurons, and dampened the over-excitation in the region. The rats had improved motor function, as seen in their balance, speed, and length of stride during walking. Moreover, the healthy "control" rats in which the cells had been transplanted took longer strides and ran faster on a runway test.
The results, the scientists say, demonstrate that the transplanted cells, known as embryonic medial ganglionic eminence (MGE) cells, can very precisely modify the balance of excitation and inhibition in neural circuits to influence behavior. As overactive neural circuits are associated with other neurodegenerative diseases a result of nonfunctioning or missing cells or abnormal synaptic transmission -- the finding may have broad implications.
"This strategy represents a whole new approach to treating nervous system disorders," says neurologist Arnold Kriegstein, MD, PhD, the senior author of the study and director of the Eli an
|Contact: Jennifer O'Brien|
University of California - San Francisco