Japanese scientists have linked atypical expression patterns of the gene FABP7, which encodes the brain fatty acid binding protein 7, with human schizophrenia. Although initially attributed to environmental abnormalities, this debilitating disease is now accepted as being influenced by a strong, yet likely multifactorial, genetic component.
The phenotypic, or behavioral, outcomes of schizophrenia are perhaps just as complicated as the genotypic alterations underlying the disease. Fortunately, suppression of a particular startle response—known as prepulse inhibition (PPI)—provides an easily measurable biological readout of the sensory motor gating mechanisms that are often impaired in schizophrenia.
In an effort to identify genes associated with schizophrenia, a team led by Takeo Yoshikawa at the RIKEN Brain Science Institute in Wako, mapped genetic alterations associated with PPI in mice1.
After tracking the PPI responses of a panel of distinct inbred mouse strains for over one year, the researchers intercrossed the strains having the lowest and highest PPI scores. Next, the team scanned the genomes of the progeny for sets of microsatellite markers, or genetic ‘tags’, and compared the presence of these tags with the PPI scores.
Using progressively rigorous sets of tags, the researchers linked impaired PPI to a region of chromosome 10 containing approximately 30 genes. The team honed in on Fabp7 (Fig. 1), one gene within this region, because of its influence over the metabolism of the polyunsaturated fatty acid DHA (docosahexaenoic acid), a process often impaired in schizophrenia.
Encouragingly, although stronger in males than in females, human schizophrenia patients exhibit abnormally high expression of FABP7 similar to mice exhibiting defective PPI responses. Notably, mice rendered genetically deficient in Fabp7 also score low in PPI measurements and display stronger behavioral responses to chronic NMDA receptor antagonist treatment, another feature of schizophrenia.
Although the team detected defects in the maintenance of neural progenitor cells in Fabp7-deficient mice, future work is needed to elucidate the precise molecular mechanism through which alterations in Fabp7 expression promote schizophrenia-like behavior in mice and humans.
Similarly, why males seem to be more strongly affected by Fabp7 over-expression remains unclear. However, sex hormone-responsive elements in the DNA regions controlling Fabp7 expression might play a role.“It is well known that malnutrition in utero increases the probability of future schizophrenia. Our results raise the importance of cohort studies to examine whether replenishment of DHA in pregnant mothers can be beneficial in reducing the chance of schizophrenia development in offspring,” says Yoshikawa.
1. Watanabe, A., Toyota, T., Owada, Y., Hayashi, T., Iwayama, Y., Matsumata, M., Ishitsuka, Y., Nakaya, A., Maekawa, M., Ohnishi, T., et al. Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype. PLoS Biology 5, 2469–2483 (2007).
Saeko Okada | ResearchSEA
For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)
New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
27.06.2017 | Power and Electrical Engineering
27.06.2017 | Information Technology
27.06.2017 | Physics and Astronomy