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!
127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere
How gut bacteria can make us ill
18.01.2017 | Helmholtz-Zentrum für Infektionsforschung
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Life Sciences
18.01.2017 | Information Technology
18.01.2017 | Life Sciences