A new international study led by the Research Institute of the McGill University Health Centre (RI-MUHC) suggests it may be. Their research has identified a molecule that improves brain function and memory recall is improved. Published in the latest issue of Cell Reports, the study has implications for neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorders and Alzheimer’s disease.
“Our findings show that the brain has a key protein called FXR1P (Fragile X Related Protein 1) that limits the production of molecules necessary for memory formation,” says RI-MUHC neuroscientist Keith Murai, the study’s senior author and Associate Professor in the Department of Neurology and Neurosurgery at McGill University. “When this brake-protein is suppressed, the brain is able to store more information.”
Murai and his colleagues used a mouse model to study how changes in brain cell connections produce new memories. When FXR1P was selectively removed from certain parts of the brain, new molecules were produced. They strengthened connections between brain cells, which correlated with improved memory and recall in the mice.
“If we can identify compounds that control the braking potential of FXR1P, we may be able to alter the amount of brain activity or plasticity. For example, in autism, one may want to decrease certain brain activity and in Alzheimer’s disease, we may want to enhance the activity. By manipulating FXR1P, we may eventually be able to adjust memory formation and retrieval, thus improving the quality of life of people suffering from brain diseases.”
The study is described in an open-access paper in Cell Reports. Funding was provided by he Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada, and U.S. National Institutes of Health.
Abstract of FXR1P Limits Long-Term Memory, Long-Lasting Synaptic Potentiation, and De Novo GluA2 Translation
Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in nonneuronal cells and colocalizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase long-term potentiation (L-LTP), and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5′ UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 that is incorporated at potentiated synapses. This study uncovers a mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity.