The rescue, described as “surprisingly complete” by the researchers, was accomplished with rapamycin, a drug known to act on a protein called mTOR whose role involves the production of other proteins.
The idea to test this drug’s effectiveness at rescuing impaired nerve cells occurred to the team as a result of having discovered a new gene that appears to act in concert with two previously identified schizophrenia susceptibility genes, one of which is involved in the activation of the protein mTOR.
This piecing together of multiple genes adds support for the idea that susceptibility to schizophrenia and autism may have common genetic fingerprints, according to the researchers.
In a report on the work published in the Sept. 24 issue of the journal Neuron, the scientists are careful to say that the genes in question are not the cause of schizophrenia or any other brain/mind disorder in humans. However, these genes do appear to serve as a blueprint for proteins that consistently pop up in a range of mental illnesses in people.
The newfound gene, dubbed KIAA1212, serves as a bridge linking two schizophrenia genes: DISC1 and AKT. Suspecting KIAA1212 as one of many potential binding partners interacting with DISC1, whose name is an acronym for “Disrupted-in-Schizophrenia,” the researchers genetically shut down the production of DISC1 proteins in newly born neurons in the hippocampus region of an adult mouse brain. The hippocampus contains a niche where native stem cells give rise to fully developed new neurons. The idea was to deliberately cause these cells to malfunction and then watch what happened.
The scientists found that the newborn neurons were most noticeably defective 14 days after DISC1 suppression and that they were defective in a variety of ways. By manipulating AKT production, or altering KIAA1212, they discovered the very same abnormalities as with DISC1 deficiency, concluding that KIAA1212 is in the same signaling pathway as DISC1 and AKT.
Because mTOR is a well-known downstream effector of AKT, they treated the adult mice harboring those abnormal neurons with rapamycin, a drug known to alleviate the effects of a faulty AKT pathway. It effectively “rescued” the neurons from their defects.
“Our discoveries give us more of the information we need to understand the function of genes associated with psychological diseases,” says Guo-li Ming, M.D., Ph.D., an associate professor of neurology and neuroscience in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. “The next step is to create a good animal model that would allow us to test whether candidate drugs will reverse not only the irregularities of brain cells with deficiency of these genes, but also behaviors.”
The new neurons with alterations of DISC1, KIAA1212 or AKT in the brains of the Rapamycin-treated mice developed normally, says Hongjun Song, Ph.D., an associate professor of Neurology in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine, who collaborated in the research. “What was amazing to us is how potent the drug is, at least on the cellular level,” he says. “A number of the neurons’ developmental defects — from enlarged cell size to the misplacement of cell localization and abnormal neuronal processes involved in receiving and sending messages — were corrected by this one drug.”
This study was supported by the National Institutes of Health, the McKnight Foundation, NARSAD, the International Mental Health Research Organization, the Maryland Stem Cell Research Fund, and the March of Dimes.
Authors on the paper, in addition to Ming and Song, are Ju Young Kim, Xin Duan, Cindy Y. Liu, Mi-Hyeon Jang, Junjie U. Guo, Nattapol Pow-anpongkul and Eunchai Kang, all of Johns Hopkins.On the Web:
Maryalice Yakutchik | EurekAlert!
Are there sustainable solutions in dealing with dwindling phosphorus resources?
16.10.2017 | Leibniz-Institut für Nutzierbiologie (FBN)
Strange undertakings: ant queens bury dead to prevent disease
13.10.2017 | Institute of Science and Technology Austria
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...
Mercury, our smallest planetary neighbor, has very little to call an atmosphere, but it does have a strange weather pattern: morning micro-meteor showers.
Recent modeling along with previously published results from NASA's MESSENGER spacecraft -- short for Mercury Surface, Space Environment, Geochemistry and...
10.10.2017 | Event News
10.10.2017 | Event News
28.09.2017 | Event News
16.10.2017 | Physics and Astronomy
16.10.2017 | Earth Sciences
16.10.2017 | Physics and Astronomy