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2017 Grants - Orr
Defining Astrocytic-Neuronal Transcriptional Alterations in Memory Loss
Anna G. Orr, Ph.D.
Joan & Sanford I. Weill Medical College of Cornell University
New York, New York
2017 Alzheimer’s Association Research Grant (AARG)
Can specialized brain cells, astrocytes, play a major role in promoting memory loss in dementia?
Astrocytes make up a large majority of the cells found in the brain, and they normally help support the function of neurons (or nerve cells). In Alzheimer’s disease, however, the chemical interactions between astrocytes and neurons become abnormal. These damaged “astrocytic-neuronal” interactions are likely associated with the development of Alzheimer’s, though scientists do not know exactly why.
In preliminary studies, Anna G. Orr, Ph.D., and colleagues found that people with Alzheimer’s disease and mice with Alzheimer’s-like brain changes had elevated levels of a protein receptor called adenosine A2A in some of their astrocytes. Protein receptors act as “docking sites” for receiving chemical messages from other cells. The researchers then found that by genetically eliminating this receptor in their mice, they could enhance the animals’ memory. They also found that abnormal receptor function in astrocytes could affect neuronal genes that are vital for memory. Taken together, these findings suggest that receptor dysfunction plays a vital role in altering astrocytic-neuronal communication — which may, in turn, alter memory-associated genes and lead to declines in memory function.
For their grant, Dr. Orr and colleagues plan to clarify the role of astrocytic-neuronal interactions in memory loss and dementia. This work will focus, in part, on how unusual astrocyte receptor activity disturbs transcription in nerve cell genes. Transcription is the process by which a gene is "activated" so that a cell begins producing the protein encoded by the gene. Dr. Orr’s team will conduct its experiments with both Alzheimer’s-like mice and with brain tissue from people who died of Alzheimer’s.
The results of this effort could improve our understanding of how astrocytes interact with neurons and contribute to Alzheimer’s disease and other dementias. These abnormal receptor interactions could possibly be novel therapeutic targets to treat dementia.