Globe-trotting biologist Kaoru Saijo began graduate studies in her native Japan, continued in Germany and finished in New York. Now in San Diego, her latest results provide a new link between inflammation and neurodegenerative diseases like Parkinson’s.

Kaoru received her medical degree from the Tokyo Medical and Dental University, but her passion for research led her to graduate school at Chiba University - at the time, combined M.D. and Ph.D. programs were uncommon in Japan. She happened to attend an immunology conference featuring German scientist Klaus Rajewsky, who brought along two of his students from the University of Cologne, one of whom fell in love with Kaoru. So in 1997 Kaoru moved to Cologne and continued her graduate research with Alexander Tarakhovsky, a group leader in Rajewsky’s lab.

Three years later Tarakhovsky got a job leading his own lab at the Rockefeller University in New York, so Kaoru and her husband moved to New York where she finally finished her Ph.D. research. (Rajewsky has since moved to Harvard.)

For those of you keeping score, that’s a Ph.D. from Chiba University.

Her husband then got a job in San Diego, so Kaoru followed.

Why not return to Japan? The environment is not “well equipped” for female scientists, Kaoru told me. Plus it’s difficult for a non-Japanese scientist to run a lab in Japan (Kaoru’s husband is German). According to Kaoru, the U.S. government supports foreign scientists very well.

In San Diego, Kaoru joined Christopher Glass’s laboratory to study how cells in the immune system work, which unexpectedly led her to Parkinson’s disease.

She and her colleagues were looking for genes in macrophages (a type of immune cell in the blood) that reduce inflammation and found that a gene named Nurr1 turns off other genes that produce an inflammatory response.

Meanwhile, Wei-dong Le and Pingyi Xu and their colleagues discovered in 2003 that mutations in Nurr1 are associated with rare cases of Parkinson’s disease, a condition in which neurons in the brain that produce dopamine deteriorate and die. Nurr1 helps control production of dopamine in neurons, and in mice missing Nurr1 researchers found a drastic reduction in the number of dopamine neurons. (We don’t know what causes most cases of the disease, which often does not run in families).

Science is all about making connections, and Kaoru cleverly observed that if Nurr1 has anti-inflammatory effects in blood cells, and Parkinson’s can be caused by improperly functioning Nurr1, then Nurr1 could be protecting the brain from inflammation - inflammation which is damaging the brain in Parkinson’s.

Kaoru’s colleague Beate Winner injected a dopamine-rich area of mouse brains with LPS, a component of bacteria that triggers inflammation. (See photo.) Dopamine neurons died - this normally takes two or three weeks. But when Beate injected LPS and a virus that turns off Nurr1, more dopamine neurons died very quickly, within one week.

Nurr1 is clearly preventing inflammation, but in which cells? Nurr1 is turned on in neurons, but it’s also turned on in microglial cells and in astrocytes, cells in the brain that are important for normal brain function. Microglial cells in the brain are thought to behave as macrophages do in the blood, defending tissue from foreign attack.

The virus that turns off Nurr1 preferentially infects astrocytes and microglia, not neurons, meaning that turning off Nurr1 in these cells, not in neurons, increased inflammation.

In other words, Nurr1 produced in microglial cells and astrocytes protects neurons from inflammation.

Scientists are finding evidence that inflammation is involved in a number of brain diseases, including Alzheimer’s disease and multiple sclerosis. Kaoru is now looking to see if Nurr1 plays a role in these diseases, and whether chemicals that activate Nurr1 could be used to treat disease.

Kaoru wants to stay in the United States and plans to apply for a faculty position here. While she misses her family in Japan, they understand her situation.

Source: “A Nurr1/CoREST Pathway in Microglia and Astrocytes Protects Dopaminergic Neurons from Inflammation-Induced Death” by Kaoru Saijo, Beate Winner, Christian T. Carson, Jana G. Collier, Leah Boyer, Michael G. Rosenfeld, Fred H. Gage and Christopher K. Glass, published on April 3 in Cell.