Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: implications for glucocorticoid neurotoxicity.
Glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, can damage the hippocampus and impair its capacity to survive coincident neurological insults. This GC endangerment of the hippocampus is energetic in nature, as it can be prevented when neurons are supplemented with additional energy substrates. This energetic endangerment might arise from the ability of GCs to inhibit glucose transport into both hippocampal neurons and astrocytes. The present study explores the GC inhibition in astrocytes. (1) GCs inhibited glucose transport approximately 15-30% in both primary and secondary hippocampal astrocyte cultures. (2) The parameters of inhibition agreed with the mechanisms of GC inhibition of glucose transport in peripheral tissues: A minimum of 4 h of GC exposure were required, and the effect was steroid specific (i.e., it was not triggered by estrogen, progesterone, or testosterone) and tissue specific (i.e., it was not triggered by GCs in cerebellar or cortical cultures). (3) Similar GC treatment caused a decrease in astrocyte survival during hypoglycemia and a decrease in the affinity of glutamate uptake. This latter observation suggests that GCs might impair the ability of astrocytes to aid neurons during times of neurologic crisis (i.e., by impairing their ability to remove damaging glutamate from the synapse).
Virgin
C E
CE
Department of Biological Sciences, Stanford University, CA 94305.
Ha
T P
TP
Packan
D R
DR
Tombaugh
G C
GC
Yang
S H
SH
Horner
H C
HC
Sapolsky
R M
RM
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000493:pharmacokinetics*; D005971:Glutamates / Q000493:pharmacokinetics*; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009420:Nervous System / Q000187:drug effects
D005938:Glucocorticoids; D005971:Glutamates; D018698:Glutamic Acid; D005947:Glucose; D003345:Corticosterone