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Glucocorticoids Inhibit Glucose Transport in Cultured Hippocampal Neurons and Glia
Abstract
A classical action of glucocorticoids (GCs) is to inhibit glucose uptake into various peripheral tissues. Two recent reports suggest that GCs do the same in the brain. Because of the in vivo nature of those studies, it was impossible to determine whether this inhibition occurred at the blood-brain barrier, and/or within neurons and glia themselves. In order to answer this and other mechanistic questions, we examined the effects of GCs on glucose transport in primary brain cultures. We established that uptake of 14C-2-deoxyglucose into hippocampal cultures was linear over a 15-min period and was inhibited by D-glucose and the uptake inhibitor cytochalasin B. Using this system, we found the following. (1) Both corticosterone and dexamethasone inhibited uptake into cultures containing both neurons and glia. (2) The effect was dose-dependent; steroid concentrations in the nanomolar range inhibited uptake from 20 to 33%. The effect was time-dependent, with more than 4 h of steroid exposure needed for inhibition. (3) Non-GC steroids did not inhibit uptake. (4) The GC inhibition seemed to be mediated by the type II (glucocorticoid) corticosteroid receptor. The effect was blocked by a type II, but not a type I (mineralocorticoid) receptor antagonist. Moreover, corticosterone inhibited only at concentrations well above the K d for the type I receptor. Finally, aldosterone inhibited transport when applied at concentrations that bound heavily to type II receptors. (5) Corticosterone did not inhibit uptake in hypothalamic, cerebellar or cortical cultures, despite the presence of corticosteroid receptors in these cultures. (6) GCs inhibited uptake in both neuron- and glia-enriched hippocampal cultures.
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“Cortisol administration reduces glucose transport into neurons (18)”
From Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly (2003) · cites this paper as [18]
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“Mechanisms by which this may occur include reduced energy metabolism that is initiated by an inhibition of glucose uptake processes (Horner et al. 1990).”
BackgroundAging in the Hippocampus: Interrelated Actions of Neurotrophins and Glucocorticoids
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“There is some evidence in hippocampal cell cultures and in peripheral tissues that glucocorticoids can inhibit glucose uptake into neurons and astrocytes (Munck, 1971; Horner et al., 1990; Virgin et al., 1991).”
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“This finding was inconsistent with the result of a (3)H-B binding assay in embryonic hippocampal cells (26) and”
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Response variability to glucose facilitation of cognitive enhancement
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Glucocorticoids Exacerbate the Deleterious Effects of gp120 in Hippocampal and Cortical Explants
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Metadata
- Authors
- Homer, H. C., Packan, D. R., & Sapolsky, R. M.
- Affiliations
- Stanford University (US)
- ORCID
- Sapolsky, Robert M.
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2008-04-03
- Volume
- 52
- Issue
- 1
- Pages
- 57-64
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W2056408203
- Cited by
- 331
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 7 · 2012: 7
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag006633-08)
- National Institute on Aging (AG-06633)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- glucocorticoids, glucose transport, glucose uptake, hippocampal neurons, glia, corticosterone, dexamethasone, aldosterone, mineralocorticoid receptor, 2-deoxyglucose, cytochalasin B, brain glucose metabolism
- MeSH terms
- Analysis of Variance, Animals, Biological Transport, Carbon Radioisotopes, Cells, Cultured, Deoxyglucose, Glucocorticoids, Glucose, Hippocampus, Immunohistochemistry, Neuroglia, Neurons, Rats, Inbred Strains, Receptors, Glucocorticoid, Rats
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