Stem cells can repair damaged circuits in the brains of mice with Parkinson's disease

  Madison, Wisconsin-Mature brains have difficulty repairing themselves after being damaged by trauma, stroke or degenerative diseases such as Parkinson's disease. The endless adaptability of stem cells offers hope for better nerve repair. But the complexity of precise adjustment of the brain hinders the development of clinical treatment.

  In a new study of these disorders, researchers at the University of Wisconsin-Madison demonstrated a proof-of-concept stem cell therapy in a mouse model of Parkinson's disease. They found that neurons derived from stem cells can integrate well into the correct areas of the brain, connect with natural neurons and restore motor function.

  The key is identity. By carefully tracking the fate of transplanted stem cells, scientists discovered that the identity of these cells (in the case of Parkinson’s disease, dopamine-producing cells) determines their connection and their functions.

  Scientists say that with more and more methods to generate dozens of unique neurons from stem cells, this work shows that neural stem cell therapy is a realistic goal. However, more research is needed to translate the findings from mice into humans.

  A research team led by UW-Madison neuroscientist Zhang Su-Chun Zhang published this discovery in the journal Cell Stem Cell on September 22. The research was led by postdoctoral researchers Chen Yuejun, Xiong Man and Tao Yezheng in Zhang's laboratory, who currently hold faculty positions in China and Singapore.

  "Our brains are connected in such a precise way through very specialized nerve cells in specific locations, so we can participate in all complex behaviors. It all depends on the circuits connected to specific cell types," said Zhang Ming, a professor of neuroscience. Department of Neurology, Wisman Center, University of Wisconsin-Madison. "Nerve damage usually affects specific brain areas or specific cell types, destroying circuits. In order to treat these diseases, we must restore these circuits."

  In order to repair these circuits in a mouse model of Parkinson's disease, the researchers first coaxed human embryonic stem cells to differentiate into dopamine-producing neurons, which die in Parkinson's disease. They transplanted these new neurons into the midbrain of mice, which is the brain area most affected by Parkinson's degeneration.

  A few months later, after the new neurons had time to integrate into the brain, the mice showed improved motor skills. On closer inspection, Zhang's team was able to see that the transplanted neurons were connected to the motor control areas of the brain over long distances. Nerve cells also establish contact with the regulatory areas of the brain that enter new neurons and prevent them from being overstimulated.

  Two sets of connections-feeding in and out of transplanted neurons-are similar to circuits built by natural neurons. This is only true for dopamine-producing cells. Similar experiments with cells that produce the neurotransmitter glutamate did not participate in the repair of Parkinson's disease, but did not repair the motor circuit, revealing the importance of neuronal identity in repairing damage.