 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 6, 2240-2244, Copyright © 1986 by Society for Neuroscience
Glucocorticoid toxicity in the hippocampus: reversal by supplementation with brain fuels
RM Sapolsky
Glucocorticoids (GCs) can damage neurons of the hippocampus, the principal
target tissue in the brain for the hormone. Hippocampal neuron loss during
aging in the rat is accelerated by prolonged GC exposure and decelerated by
adrenalectomy. GCs appear to damage these neurons indirectly by inducing a
state of vulnerability and thus impairing their capacity to survive a
variety of metabolic challenges. As such, high physiological concentrations
of the steroid increase hippocampal damage induced by an antimetabolite
toxin, an excitotoxin, or hypoxia-ischemia. Conversely, adrenalectomy
attenuates the damage caused by these insults. This study suggests that GCs
endanger hippocampal neurons by impairing their energy metabolism. Neurons
are extremely vulnerable to such disruption, all the insults potentiated by
GCs either impair energy production or pathologically increase energy
consumption, and GCs inhibit glucose utilization in the hippocampus.
Administration of different brain fuels--glucose, mannose, fructose, or the
ketone beta-hydroxybutyrate--reduced hippocampal damage induced by
coadministration of GCs and either of 2 different neurotoxins (kainic acid
and 3-acetylpyridine). This appeared to be due to a reduction in the
damaging synergy between GCs and the toxin; as evidence, a dose of mannose
that attenuated damage induced by kainic acid plus GCs failed to reduce
damage induced by the same dose of kainic acid alone. Glucose (whose
utilization is noncompetitively inhibited by GCs) and fructose (which does
not readily penetrate the blood-brain barrier) were less effective at
reducing damage than the other 2 fuels.
This article has been cited by other articles:
|
|
|
|
 
P. Casolini, M. R. Domenici, C. Cinque, G. S. Alema, V. Chiodi, M. Galluzzo, M. Musumeci, J. Mairesse, A. R. Zuena, P. Matteucci, et al.
Maternal Exposure to Low Levels of Corticosterone during Lactation Protects the Adult Offspring against Ischemic Brain Damage
J. Neurosci.,
June 27, 2007;
27(26):
7041 - 7046.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Lucassen, M. B. Muller, F. Holsboer, J. Bauer, A. Holtrop, J. Wouda, W. J. G. Hoogendijk, E. R. De Kloet, and D. F. Swaab
Hippocampal Apoptosis in Major Depression Is a Minor Event and Absent from Subareas at Risk for Glucocorticoid Overexposure
Am. J. Pathol.,
February 1, 2001;
158(2):
453 - 468.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Krugers, S. Maslam, J. Korf, M. Joels, and F. Holsboer
The Corticosterone Synthesis Inhibitor Metyrapone Prevents Hypoxia/Ischemia-Induced Loss of Synaptic Function in the Rat Hippocampus Editorial Comment
Stroke,
May 1, 2000;
31(5):
1162 - 1172.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Sapolsky, L. M. Romero, and A. U. Munck
How Do Glucocorticoids Influence Stress Responses? Integrating Permissive, Suppressive, Stimulatory, and Preparative Actions
Endocr. Rev.,
February 1, 2000;
21(1):
55 - 89.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. M. Magarinos, J. M. G. Verdugo, and B. S. McEwen
Chronic stress alters synaptic terminal structure in hippocampus
PNAS,
December 9, 1997;
94(25):
14002 - 14008.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. de Leon, T. McRae, H. Rusinek, A. Convit, S. De Santi, C. Tarshish, J. Golomb, N. Volkow, K. Daisley, N. Orentreich, et al.
Cortisol Reduces Hippocampal Glucose Metabolism in Normal Elderly, but Not in Alzheimer's Disease
J. Clin. Endocrinol. Metab.,
October 1, 1997;
82(10):
3251 - 3259.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Harvey, G. Healing, I. Major, M. McFarlane, K. Purdy, O. Olatunde, M. Garcia Conesa, D. Everett, and A. Cockburn
Glucocorticoid amelioration of nephrotoxicity: a study of cephaloridine- methylprednisolone interaction in the rat
Human and Experimental Toxicology,
July 1, 1995;
14(7):
554 - 561.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. Evans
The steroid and thyroid hormone receptor superfamily
Science,
May 13, 1988;
240(4854):
889 - 895.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Meaney, D. Aitken, C van Berkel, S Bhatnagar, and R. Sapolsky
Effect of neonatal handling on age-related impairments associated with the hippocampus
Science,
February 12, 1988;
239(4841):
766 - 768.
[Abstract]
[PDF]
|
|
|
|
Compound via MeSH
