Protein affecting development of learning ability identified
α-chimaerin exhibits a wide range of effects on brain functions
There are more than 100 billion neurons in our brains. They elongate neurites and connect with each other and form neuronal circuits, serving high-level functions such as memory, learning, reasoning, problem solving, and language. It is thought that these neuronal circuits are formed during development and support brain functions in adulthood; however, what molecules are involved through what mechanism has been unknown. A group of researchers paid attention to α-chimaerin, a protein, and examined how and when isoforms of this protein affected brain function.
• Division of Neurogenetics, National Institute of Genetics -- IWATA Ryohei (Fellow), IWASATO Takuji (Professor)
• Brain Science Institute, Riken -- ITOHARA Shigeyoshi (Senior Team Leader)
• United Graduate School of Child Development, Osaka University -- HASHIMOTO Ryota (Associate Professor)
There are two types of α-chimaerin: α1 isoform (α1-chimaerin) and α2 isoform (α2-chimaerin). This group made genetically modified mice and conducted behavioral experiments using those mice. Their results showed that mice in which both types of α-chimaerin were not functioning were as much as 20 times more active than normal mice. The learning of these mice was enhanced in adulthood. The learning ability of mice in which only α1 isoform was lacking and that of mice in which α1 and α2 isoforms were lacking in adulthood were normal. That is, α2-chimaerin played a key role in learning ability during development.
This group also examined, in healthy people, the relationship between α-chimaerin gene type (Single-nucleotide polymorphisms (SNPs)) and characters and abilities. It was found that in persons having a specific type of base near α2-chimaerin gene, a certain tendency to autism was observed and their arithmetic ability was high.
These findings suggest: (1) α-chimaerin is responsible for controlling a wide range of brain functions such as amount of activity and learning function, (2) α-chimaerin during development affects learning function in adulthood, and (3) α-chimaerin is related to individual difference of brain function in humans. This group's achievement will be helpful in clarifying how α-chimaerin is related to learning disabilities and mental diseases as well as to how such conditions develop.
A major concern in neuroscience is how cognitive ability in adulthood is affected and regulated by developmental mechanisms. The molecular bases of cognitive development are not well understood. We provide evidence for the involvement of the α2 isoform of Rac-specific guanosine triphosphatase (GTPase)-activating protein (RacGAP) α-chimaerin (chimerin) in this process. We generated and analyzed mice with global and conditional knockouts of α-chimaerin and its isoforms (α1-chimaerin and α2-chimaerin) and found that α-chimaerin plays a wide variety of roles in brain function and that the roles of α1-chimaerin and α2-chimaerin are distinct. Deletion of α2-chimaerin, but not α1-chimaerin, beginning during early development results in an increase in contextual fear learning in adult mice, whereas learning is not altered when α2-chimaerin is deleted only in adulthood. Our findings suggest that α2-chimaerin acts during development to establish normal cognitive ability in adulthood.
To learn more about this research, please view the full research report entitled " RacGAP α2-Chimaerin Function in Development Adjusts Cognitive Ability in Adulthood " at this page of the Cell Reports website.
Related links :
• Molecular Psychiatry Research Group, Department of Psychiatry, Graduate School of Medicine, Osaka University
• Molecular Research Center for Children's Mental Development, United Graduate School of Child Development Medicine , Osaka University
• Department of Psychiatry, Graduate School of Medicine, Osaka University