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!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy