Using diverse methodologies, neuroscientists from the RIKEN Brain Science Institute report that defects in Fatty Acid Binding Proteins (FABPs) may help to explain the pathology in some cases of schizophrenia and autism spectrum disorders.
After identifying mutations in FABPs from patients, the group led by Senior Team Leader Takeo Yoshikawa determined that the genetic disruption of Fabps in mice mimics disease behaviors seen in patients. This work suggests that disruption of FABPs could be a common link underlying some forms of these two prevalent mental disorders.
Published in the journal Human Molecular Genetics, the study reported that fatty acid binding proteins (FABPs), a component of lipid metabolism, are genetically linked to schizophrenia and autism spectrum disorder (ASD) in humans and dysfunctional behaviors in mice. The findings provide support for the involvement of lipid metabolism in the spectrum of cognitive disorders.
The brain is composed of lipids that provide structure and signaling functions, and disruption of lipid transport to or within the brain can lead to anomalous neurological symptoms.
Previous studies revealed abnormally low levels of some polyunsaturated fatty acids (PUFAs) including essential fatty acids in schizophrenic and autistic patients but failed to identify the responsible proteins. Consequently, Yoshikawa and his team decided to investigate FABPs ? molecules that facilitate the transport of PUFAs and other fatty acids.
"Our prior study showed that disruption of Fabp7 in mice impaired neurogenesis, so we suspected that FABP7 and its family members had important roles in neurodevelopment", said Dr. Yoshikawa. The researchers focused on the major FABPs found in mature neurons and neuronal progenitors, FABP3, FABP5, and FABP7, to better understand their potential roles in mental disabilities.
The team found that the expression levels of FABPs in postmortem brain and blood cells of patients were altered. Using molecular analysis, the team identified specific mutations in FABP genes exclusively in patients, which caused an abnormal structure or function of these proteins, presumably preventing them from delivering the correct fatty acids to their target tissues and organelles inside cells.
To investigate the effect of Fabp loss in the brain, the researchers genetically inactivated the genes in mice and conducted behavioral tests. They found that mice lacking Fabps exhibited behaviors similar to those observed in human patients. Fabp3 knock-out mice showed a decrease in memory and social motivation, mirroring dysfunctional cognition and lack of interest in social communication in ASD patients.
In contrast, Fabp7 knock-out mice displayed hyperactivity and anxiety, a phenotype similar to that observed in schizophrenic patients. "Although the amino acid sequence of the FABPs is similar, we think that they interact with different fatty acids and are expressed in different cells with distinct timing during development. This is likely the reason that the behaviors in the mice are different for each member of the Fabp family", said Dr. Yoshikawa.
Both schizophrenia and ASD are caused by many factors and conventional treatment does not work well on all patients. These findings suggest that FABPs may define one mechanism for these disorders selectively affecting lipid transport systems that may complement other etiological factors.
"Identification of FABP mutations in humans may to help us take a personalized treatment approach," said Dr. Yoshikawa. "We hope our finding will lead to the development of tailor-made therapies, providing patients with molecules that complement deficiencies caused by their particular mutation."
Jens Wilkinson | Eurek Alert!
Pathogenic bacteria hitchhiking to North and Baltic Seas?
22.07.2016 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung
Unconventional quasiparticles predicted in conventional crystals
22.07.2016 | Max-Planck-Institut für Chemische Physik fester Stoffe
Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.
Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...
Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases
Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...
Scaffolding and specialised workers help with the delivery – Heidelberg biochemists gain new insights into biogenesis
A type of scaffolding on which specialised workers ply their trade helps in the manufacturing process of the two subunits from which the ribosome – the protein...
Scientists at the Helmholtz Zentrum München have developed a new mass spectrometry imaging method which, for the first time, makes it possible to analyze hundreds of metabolites in fixed tissue samples. Their findings, published in the journal Nature Protocols, explain the new access to metabolic information, which will offer previously unexploited potential for tissue-based research and molecular diagnostics.
In biomedical research, working with tissue samples is indispensable because it permits insights into the biological reality of patients, for example, in...
Chemists at the University of Basel have succeeded in using computer simulations to elucidate transient structures in proteins. In the journal Angewandte Chemie, the researchers set out how computer simulations of details at the atomic level can be used to understand proteins’ modes of action.
Using computational chemistry, it is possible to characterize the motion of individual atoms of a molecule. Today, the latest simulation techniques allow...
15.07.2016 | Event News
15.07.2016 | Event News
11.07.2016 | Event News
22.07.2016 | Information Technology
22.07.2016 | Physics and Astronomy
22.07.2016 | Life Sciences