May 25, 2012
Researchers identify Key Behavioral Protein
(Ivanhoe Newswire) -- Behavioral flexibility allows us to modify our behaviors to adjust to circumstances that are similar, but not identical, to previous experiences. Now, a protein necessary for individuals to maintain that flexibility has been identified.
The findings may offer new insights into addressing autism and schizophrenia, both of which are known for impaired behavioral inflexibility. Our behavioral flexibility allows us to make necessary changes and, then, successfully complete our task. It is driven, in part, by protein synthesis, which produces experience-dependent changes in neural function and behavior.
However, this process is impaired for many, preventing an adjustment in behavior when faced with different circumstances. In the Cell Reports study, the researchers sought to understand how protein synthesis is regulated during behavioral flexibility.
To do so, they focused on the kinase PERK, an enzyme that regulates protein synthesis. PERK is known to modify eIF2alpha, a factor that is required for proper protein synthesis. Their experiments involved comparing normal lab mice, which possessed the enzyme, with those that lacked it.
The mice were asked to navigate a water maze, which involved elevating themselves onto a platform in order to get out of the water. Both the normal mice and those lacking PERK learned to complete this task.
However, in the second stage of the study, the mice's behavioral flexibility was tested by moving the maze's platform to a different location, requiring them to respond to change in the terrain. The normal mice successfully located the platform, whereas those lacking PERK were unable to locate the platform or took significantly longer to do so.
A second experiment was conducted which showed the same results. The researchers sought additional support for their conclusion that the absence of PERK may contribute to impaired behavioral flexibility in human neurological disorders. To do so, they conducted postmortem analyses of human frontal cortex samples from patients afflicted with schizophrenia, who often exhibit behavioral inflexibility, and unaffected individuals. The samples from the control group showed normal levels of PERK while those from the schizophrenic patients had significantly reduced levels of the protein.
"A rapidly expanding list of neurological disorders and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Fragile X syndrome, have already been linked to aberrant protein synthesis," Eric Klann, a professor in NYU's Center for Neural Science and one of the study's co-authors, was quoted saying. "Our results show the significance of PERK in maintaining behavioral flexibility and how its absence might be associated with schizophrenia. Further studies clarifying the specific role of PERK-regulated protein synthesis in the brain may provide new avenues to tackle such widespread and often debilitating neurological disorders."
Source: Cell Reports, May 2012