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Researchers identify protein necessary for behavioral flexibility - Pharma Raw Material by fdhjkl rfghjtkl





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Researchers identify protein necessary for behavioral flexibility - Pharma Raw Material by
Article Posted: 02/20/2013
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Researchers identify protein necessary for behavioral flexibility - Pharma Raw Material


 
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Researchers have identified a protein necessary to maintainbehavioral flexibility, which allows us to modify our behaviors toadjust to circumstances that are similar, but not identical, toprevious experiences. Their findings, which appear in the journalCell Reports, may offer new insights into addressing autism and schizophrenia - afflictions marked by impaired behavioral flexibility. Our stored memories from previous experiences allow us to repeatcertain tasks. For instance, after driving to a particularlocation, we recall the route the next time we make that trip.However, sometimes circumstances change - one road on the route istemporarily closed - and we need to make adjustments to reach ourdestination.

Our behavioral flexibility allows us to make suchchanges and, then, successfully complete our task. It is driven, inpart, by protein synthesis, which produces experience-dependentchanges in neural function and behavior. However, this process is impaired for many, preventing anadjustment in behavior when faced with different circumstances. Inthe Cell Reports study, the researchers sought to understand howprotein synthesis is regulated during behavioral flexibility. To do so, they focused on the kinase PERK, an enzyme that regulatesprotein synthesis.

PERK is known to modify eIF2alpha, a factor thatis required for proper protein synthesis. Their experimentsinvolved comparing normal lab mice, which possessed the enzyme,with those that lacked it. In their study, the mice were asked to navigate a water maze, whichincluded elevating themselves onto a platform to get out of thewater. Normal mice and those lacking PERK learned to complete thistask.

However, in a second step, the researchers tested the mice'sbehavioral flexibility by moving the maze's platform to anotherlocation, thereby requiring them to respond to a change in theterrain. Here, the normal mice located the platform, but thoselacking PERK were unable to do so or took significantly more timeto complete the task. A second experiment offered a different test of the role of PERK inaiding behavioral flexibility. In this measure, both normal andmutant mice heard an audible tone that was followed by a mild footshock.

At this stage, all of the mice developed a normal fearresponse - freezing at the tone in anticipation of the foot shock.However, the researchers subsequently removed the foot shock fromthe procedure and the mice heard only the tone. Eventually, thenormal mice adjusted their responses so they did not freeze afterhearing the tone. However, the mutant mice continued to respond asif they expected a foot shock to follow. The researchers sought additional support for their conclusion thatthe absence of PERK may contribute to impaired behavioralflexibility in human neurological disorders. To do so, theyconducted postmortem analyses of human frontal cortex samples frompatients afflicted with schizophrenia, who often exhibit behavioralinflexibility, and unaffected individuals.

The samples from thecontrol group showed normal levels of PERK while those from theschizophrenic patients had significantly reduced levels of theprotein. "A rapidly expanding list of neurological disorders andneurodegenerative diseases, including Alzheimer's disease , Parkinson's disease , and Fragile X syndrome, have already been linked to aberrantprotein synthesis," explained Eric Klann, a professor in NYU'sCenter for Neural Science and one of the study's co-authors. "Ourresults show the significance of PERK in maintaining behavioralflexibility and how its absence might be associated withschizophrenia. Further studies clarifying the specific role ofPERK-regulated protein synthesis in the brain may provide newavenues to tackle such widespread and often debilitatingneurological disorders." Additional References Citations.

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