15 Apr Important Protein Pathway In Brain Plasticity Identified
MedicalResearch.com Interview with:
Erwin G. Van Meir, PhD
Professor, Departments of Neurosurgery and Hematology & Medical Oncology Leader, Winship Cancer Institute Cancer Cell Biology Program
Founding Director, Graduate Program in Cancer Biology
Director, Laboratory for Molecular Neuro-Oncology
Emory University School of Medicine Atlanta GA 30322
Medical Research: What is the background for this study? What are the main findings?
Dr. Van Meir: In this study we queried the role of the BAI1 protein in normal physiology. To do this we generated a transgenic mouse, which lacks the expression of the Bai1 gene. The mice had no obvious anomalies and reproduced according to mendelian rules. Since BAI1 is strongly expressed in the brain, including in neurons, we wondered whether they might have some cognitive defect that would only be revealed under specific testing conditions. We had the mice perform in an experiment that tests their ability to orient themselves in space and memorize the location of a hidden platform in a water maze. This experiment clearly demonstrated that the Bai1 deficient mice had deficits in spatial learning and memory. We then further probed the electrophysiological, anatomical and biochemical basis of this abnormal physiologic behavior and showed that hippocampal neurons had abnormal synaptic plasticity, reduced thickness of the post synaptic density and that this was associated with an increased degradation of a key PSD protein called PSD-95.
Medical Research: What should clinicians and patients take away from your report?
Dr. Van Meir: This is basic research that helps define the role of an abundantly expressed protein in the brain. However, the type of neurological deficits we uncovered in these mice are also observed in a number of human diseases. A number of psychiatric and neurological conditions, including schizophrenia and autism display dysregulation of dendritic spines and synaptic plasticity. Thus the BAI1 pathway represents a novel target for therapeutics in the treatment of such disorders. The good news was that we were able to restore the abnormal electrophysiological response in the hippocampal neurons of the mice through viral gene therapy. This means that a defect occurring during development can still be corrected later in life providing hope for patients that such conditions are not irreversible, and that therapeutic strategies will become possible in the future.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Van Meir: Our study is a milestone in our understanding of the function of BAI1 in the brain, especially in the hippocampus. Further studies will have to examine whether the protein plays important roles in other parts of the brain. Also, a lot is still to be learned about the molecular signals emanating from the BAI1 receptor, what ligands bind to it and what molecular partners are involved in the transmitting the downstream molecular signaling.
Citation:
Dan Zhu, Chenchen Li, Andrew M. Swanson, Rosa M. Villalba, Jidong Guo, Zhaobin Zhang, Shannon Matheny, Tatsuro Murakami, Jason R. Stephenson, Sarah Daniel, Masaki Fukata, Randy A. Hall, Jeffrey J. Olson, Gretchen N. Neigh, Yoland Smith, Donald G. Rainnie, Erwin G. Van Meir. BAI1 regulates spatial learning and synaptic plasticity in the hippocampus. Journal of Clinical Investigation, 2015; DOI: 10.1172/JCI74603
Last Updated on April 15, 2015 by Marie Benz MD FAAD