Local Cerebral Glucose Utilization Is Increased in Acutely Adrenalectomized Rats

Kadekaro, Massako; Ito, Masanori; Gross, Paul M.

doi:10.1159/000124933

Cited by 156 publications

(70 citation statements)

References 39 publications

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“…For example, glucocorticoids have been shown to decrease local cerebral glucose utilization in vivo 27 and inhibit glucose transport in neurons in vitro. 28 By impairing glucose transport, glucocorticoids cause a subsequent ATP depletion and increased neuronal vulnerability to excitotoxicity (reviewed by Sapolsky 29 ).…”

Section: Discussionmentioning

confidence: 99%

Social Stress Exacerbates Focal Cerebral Ischemia in Mice

Sugo

Hurn

Morahan

et al. 2002

Stroke

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Background and Purpose-The purpose of the present study was to determine whether exposure to stress or elevated corticosterone concentrations in the days preceding cerebral ischemia exacerbates ischemic injury as assessed by histological and behavioral outcomes. Methods-For 7 consecutive days, male C57/BL6 mice were exposed to social stress for 45 minutes or injected with 1 mg/kg corticosterone or vehicle. The animals exposed to social stress were injected with either 1 mg/kg mifepristone, a glucocorticoid receptor antagonist, or the vehicle 30 minutes before stress. On the seventh day, all animals were trained in a passive avoidance task. Twenty-four hours after training, the animals were subjected to 60 minutes of intraluminal middle cerebral artery occlusion (MCAO) or sham surgery. At 72 hours of reperfusion, the animals were tested for retention of the passive avoidance task, and infarction size was determined. Results-Animals subjected to chronic social stress or treated with exogenous corticosterone before MCAO exhibited larger infarcts and reduced retention of passive avoidance compared with the nonstressed MCAO control. The effects of social stress on infarct volume and passive avoidance were reversed by pretreatment with mifepristone. There was no difference between stressed and control groups in physiological parameters or reduction of laser-Doppler flow signal during MCAO or reperfusion. Conclusions-Prior exposure to social stress increases infarction volume and exacerbates cognitive deficits associated with transient cerebral ischemia. The mechanism underlying the effects of stress on stroke outcome likely involves corticosterone acting through glucocorticoid receptors to increase subsequent ischemia-induced neuronal death. (Stroke.

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Section: Discussionmentioning

confidence: 99%

Social Stress Exacerbates Focal Cerebral Ischemia in Mice

Sugo

Hurn

Morahan

et al. 2002

Stroke

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“…The GC-induced mobilization of energy to muscle and away from other tissues, including the brain, is well understood as part of the adaptation to an acute, stressful emergency. This means, however, that corticosteroid receptor-rich regions such as the hippocampus (Jacobson et al, 1993) experience a decrease in glucose transport when GC levels are high (Kadekaro et al, 1988;Homer et al, 1990). To test the hypothesis that GCs exacerbate gpl2O neurotoxicity by reducing available energy, we measured the energy levels of rons and glia, the results are still highly relevant.…”

Section: The Cells In the Mitochondrial Potential Experimentsmentioning

confidence: 99%

“…However, the mechanism most relevant to the present study is GCs' ability to decrease glucose transport into hippocampal neurons, most likely by decreasing the number of glucose transporters at the membrane (Kadekaro et al, 1988;Homer et al, 1990). This has been shown to be associated with a faster decline in mitochondnal potentials and ATP concentrations during insults (Tombaugh and Sapolsky, 1990;Lawrence and Sapolsky, 1994); as a measure ofthe important consequences of these disruptive energetic effects of GCs, the steroids no longer exacerbate the toxicity of neurological insults when neurons are supplemented with excess energy (Virgin et al, 1991;.…”

mentioning

confidence: 97%

Energy Dependency of Glucocorticoid Exacerbation of gp120 Neurotoxicity

Brooke

Howard

Sapolsky

1998

Journal of Neurochemistry

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Abstract:The HIV envelope glycoprotein, gpl 20, a well documented neurotoxin, may be involved in AIDS-related dementia complex. gpl2O works through an NMDA receptor-and calcium-dependent mechanism to damage neurons. We have previously demonstrated that both natural and synthetic glucocorticoids (GCs) exacerbate gpl 20-induced neurotoxicity and calcium mobilization in hippocampal mixed cultures. GCs, steroid hormones secreted during stress, are now shown to work in conjunction with gpl 20 to decrease ATP levels and to work synergistically with gpl2O to decrease the mitochondrial potential in hippocampal cultures. Furthermore, energy supplementation blocked the ability of GCs to worsen gpl2O's effects on neuronal survival and calcium mobilization. A GC-induced reduction in glucose transport in hippocampal neurons, as previously documented, may contribute to this energetic dependency. These results may have clinical significance, considering the common treatment of severe cases of Pneumocystis carinii pneumonia, typical of HIV infection, with large doses of synthetic GCs. Key Words: Glucocorticoids-Stress-AIDS-related dementia-Neurotoxicity-Calcium-Hippocampus-gpl 20.

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“…In addition, an enhancement of daily food intake can also be seen with ventricular injections of ALDO (181). While measures of metabolic parameters have yet to be taken in studies with centrally administered steroids, such actions are likely in light of evidence that CORT's glucoregulatory effects, including the inhibition of glucose uptake and utilization, occur similarly in the brain as in the periphery (16,167,168,182).…”

Section: Differential Role Of Steroid Receptor Subtypes In Nutrient Imentioning

confidence: 99%

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

194

127

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The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle.Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 pg%) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-1 0 pg%) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further ( > 10 pg%) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle.Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term. Moreover, under conditions of obesity, diabetes and food restriction, steroid receptor function is greatly disturbed in association with chronic high circulating levels of CORT and abnormal glucose homeostasis. These disturbances in steroid action, along with dysfunction in brain neurochemical processes, very possibly contribute to the maintenance of hyperphagia and body weight gain in obese and diabetic ...

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Local Cerebral Glucose Utilization Is Increased in Acutely Adrenalectomized Rats

Cited by 156 publications

References 39 publications

Social Stress Exacerbates Focal Cerebral Ischemia in Mice

Social Stress Exacerbates Focal Cerebral Ischemia in Mice

Energy Dependency of Glucocorticoid Exacerbation of gp120 Neurotoxicity

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

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