Glucocorticoid receptor signaling in astrocytes is required for aversive memory formation
Transl Psychiatry. 2018-11-28; 8(1):
DOI: 10.1038/s41398-018-0300-x
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Stress elicits the release of glucocorticoids (GCs) that regulate energy
metabolism and play a role in emotional memory. Astrocytes express glucocorticoid
receptors (GR), but their contribution to cognitive effects of GC’s action in the
brain is unknown. To address this question, we studied how astrocyte-specific
elimination of GR affects animal behavior known to be regulated by stress. Mice
with astrocyte-specific ablation of GR presented impaired aversive memory
expression in two different paradigms of Pavlovian learning: contextual fear
conditioning and conditioned place aversion. These mice also displayed
compromised regulation of genes encoding key elements of the glucose metabolism
pathway upon GR stimulation. In particular, we identified that the glial, but not
the neuronal isoform of a crucial stress-response molecule, Sgk1, undergoes
GR-dependent regulation in vivo and demonstrated the involvement of SGK1 in
regulation of glucose uptake in astrocytes. Together, our results reveal
astrocytes as a central element in GC-dependent formation of aversive memory and
suggest their relevance for stress-induced alteration of brain glucose
metabolism. Consequently, astrocytes should be considered as a cellular target of
therapies of stress-induced brain diseases.
DOI: 10.1038/s41398-018-0300-x
PMCID: PMC6261947
PMID: 30487639 [Indexed for MEDLINE]