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Nat Neurosci. 2015 Mar;18(3):423-34. doi: 10.1038/nn.3930. Epub 2015 Jan 26.

Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory.

Author information

1
1] Gladstone Institute of Neurological Disease, San Francisco, California, USA. [2] Department of Neurology, University of California, San Francisco, California, USA.
2
1] Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA. [2] Division of Endocrinology and Metabolism, Department of Medicine, and the Institute for Human Genetics, University of California, San Francisco, California, USA.
3
Gladstone Institute of Neurological Disease, San Francisco, California, USA.
4
1] Department of Neuroscience, University of California, San Diego, La Jolla, California, USA. [2] Department of Pathology, University of California, San Diego, La Jolla, California, USA.
5
1] Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA. [2] Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA.

Abstract

Astrocytes express a variety of G protein-coupled receptors and might influence cognitive functions, such as learning and memory. However, the roles of astrocytic Gs-coupled receptors in cognitive function are not known. We found that humans with Alzheimer's disease (AD) had increased levels of the Gs-coupled adenosine receptor A2A in astrocytes. Conditional genetic removal of these receptors enhanced long-term memory in young and aging mice and increased the levels of Arc (also known as Arg3.1), an immediate-early gene that is required for long-term memory. Chemogenetic activation of astrocytic Gs-coupled signaling reduced long-term memory in mice without affecting learning. Like humans with AD, aging mice expressing human amyloid precursor protein (hAPP) showed increased levels of astrocytic A2A receptors. Conditional genetic removal of these receptors enhanced memory in aging hAPP mice. Together, these findings establish a regulatory role for astrocytic Gs-coupled receptors in memory and suggest that AD-linked increases in astrocytic A2A receptor levels contribute to memory loss.

PMID:
25622143
PMCID:
PMC4340760
DOI:
10.1038/nn.3930
[Indexed for MEDLINE]
Free PMC Article

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