Could an astrocyte receptor explain some of the memory deficits of Alzheimer’s disease? So suggest scientists in the January 26 Nature Neuroscience. Researchers led by Lennart Mucke of Gladstone Institute of Neurological Disease, San Francisco, report that in people with advancing AD, astrocytes ramp up production of the G protein-coupled adenosine receptor A2A (see image). First author Anna Orr presented the findings at the 2014 Society for Neuroscience annual meeting in Washington, D.C. (see Dec 2014 conference news).
The scientists found that knocking out the A2A receptor from astrocytes improved memory in young and old mice. Deleting A2A elevated expression of the immediate-early gene Arc in the dentate gyrus and cortex. The Arc protein facilitates long-term memory. The conditional A2A knockout also improved memory in 16-month-old transgenic mice expressing the human amyloid precursor protein. Conversely, stimulating Gs-coupled signaling in astrocytes of the hippocampus in 2-month-old mice blocked spatial memories formed in the Morris water maze.
How does the A2A receptor modulate memory? The researchers propose it might be involved in the process of actively forgetting. They suggest astrocytic A2A receptors could be therapeutic targets in AD.—Gwyneth Dickey Zakaib
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