Abstract
The paradox that increased levels of glucocorticoids can either enhance or suppress the organism's defense against stress, has been an obstacle to formulating a unified picture of glucocorticoid function. To clarify the glucocorticoid paradox, we examined male Sprague-Dawley rats exposed to immobilization stress and/or bilateral adrenalectomy (ADX), and measured oxidative damage to lipid, protein, and DNA, as well as monoamine neurotransmitter turnover. ADX, which is similar to stress, induces an increase in lipid peroxidation and protein oxidation, accompanied by increased monoamine neurotransmitter turnover in several regions of the brain of rats. The effect of ADX is greater than that induced by short-term immobilization stress. In addition, ADX enhances stress-induced oxidative damage and increase of monoamine neurotransmitter turnover. These results, together with our previous finding that long-term stress causes oxidative damage to the brain, suggest that stress levels of glucocorticoids, or levels lower than basal, cause oxidative damage. However, basal levels of glucocorticoids appear to buffer against oxidative damage. These findings provide possible mechanisms to understand the glucocorticoid paradox, and support the stress-oxidative hypothesis of aging acceleration.
Similar content being viewed by others
REFERENCES
Adachi, S., Kawamura, K., & Takemoto, K. (1993). Oxidative damage of nuclear DNA in liver of rats exposed to psychological stress. Cancer Research, 53, 4153–4155.
Andine, P., Orwar, O., Jacobson, I., Sandberg, M., & Hagberg, H. (1991). Changes in extracellular amino acids and spontaneous neuronal activity during ischemia and extended reflow in the CA1 of the rat hippocampus. Journal of Neurochemistry, 57, 222–229.
Bertini, R., Bianchi, M., & Ghezzi, P. (1988). Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor. Journal of Experimental Medicine, 167, 1708–1712.
Bodnoff, S. R., Humphreys, A. G., Lehman, J. C., Diamond, D. M., Rose, G. M., & Meaney, M. J. (1995). Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats. Journal of Neuroscience, 15, 61–69.
Bondy, S. C., & LeBel, C. P. (1993). The relationship between excitotoxicity and oxidative stress in the central nervous system. Free Radical Biology & Medicine, 14, 633–642.
Brackan, M., Shepard, M., & Collins, W. (1990). A randomized controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury. New England Journal of Medicine, 322, 1405–1411.
Burch, R. M., Connor, J. R., & Axelrod, J. (1988). Interleukin 1 amplifies receptor-mediated activation of phospholipase A2 in 3T3 fibroblasts. Proceedings of the National Academy of Science USA, 85, 6306–6309.
Carpenter, W. T., & Gruen, P. H. (1984). The limbic-hypothalmic-pituitary-adrenal system and human behavior. In L. L. Iversen, S. D. Iversen, & S. H. Snyder (Eds.), Handbook of psychopharmacology, (pp. 109–143). New York: Plenum.
Choi, D. W. (1988). Glutamate neurotoxicity and diseases of the nervous system. Neuron, 1, 623–634.
Choi, D. W. (1992a). Bench to bedside: The glutamate connection. Science, 258, 241–243.
Choi, D. W. (1992b). Excitotoxic cell death. Journal of Neurobiology, 23, 1261–1276.
Cohen, G. (1983). The pathobiology of Parkinson's disease: Biochemical aspects of dopamine neuron senescence. Journal of Neurol Transmission, 19(Suppl.), 89–103.
Coyle, J. T., & Puttfarcken, P. (1993). Oxidative stress, glutamate, and neurodegenerative disorders. Science, 262, 689–695.
Djouadi, F., Wijkhuisen, A., Bastin, J., Vilar, J., & Merlet-Benichou, C. (1993). Effect of glucocorticoids on mitochondrial oxidative enzyme and Na/K-ATPase activities in the rat proximal tubule and thick ascending limb of Henle. Renal Physiology & Biochemistry, 16, 249–256.
Dugan, L. L., & Choi, D. W. (1994). Excitotoxicity, free radicals, and cell membrane changes. Annual Neurology, S17–21.
Faulk, E. A., McCully, J. D., Tsukube, T., Hadlow, N. C., Krukenkamp, I. B., & Levitsky, S. (1995). Myocardial mitochondrial calcium accumulation modulates nuclear calcium accumulation and DNA fragmentation. Annals of Thoracal Surgery, 60, 338–344.
Feng, L., Xia, Y., Garcia, G. E., Hwang, D., & Wilson, C. B. (1995). Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide. Journal of Clinical Investigation, t95, 1669–1675.
Glavin, G. B. (1985). Stress and brain noradrenaline: A review. Neuroscience and Biobehavioral Review, 9, 233–243.
Glowinski, J., & Iverson, L. (1966). Regional studies of catecholamine in the rat brain. Journal of Neurochemistry, 13, 655–669.
Halliwell, B. (1992). Reactive oxygen species and the central nervous system. Journal of Neurochemistry, 59, 1609–1623.
Hruza, L. L., & Pentland, A. P. (1993). Mechanisms of UV-induced inflammation. Journal of Investigative Dermatology, 100, 35S–41S.
Issa, A. M., Rowe, W., Gauthier, S., & Meaney, M. J. (1990). Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats. Journal of Neuroscience, 10, 3247–3254.
Itoh, T., Saito, T., Fujimura, M., Watanabe, S., & Saito, K. (1993). Restraint stress-induced changes in endogenous zinc release from the rat hippocampus. Brain Research, 618, 318–322.
Kabuto, H., Yokoi, I., & Mori, A. (1992). Monoamine metabolites, iron induced seizures, and the anticonvulsant effect of tannins. Neurochemical Research, 17, 585–590.
Kvetnansky, R., & Mikulaj, L. (1970). Adrenal and urinary catecholamines in rats during adaptation to repeated immobilization stress. Endocrinology, 87, 738–743.
Landfield, P. W., & Eldridge, J. C. (1994). Evolving aspects of the glucocorticoid hypothesis of brain aging: Hormonal modulation of neuronal calcium homeostasis. Neurobiology of Aging, 15, 579–588.
Levine, R. L., Williams, J. A., Stadtman, E. R., & Shacter, E. (1994). Carbonyl assays for determination of oxidatively modified proteins. Methods in Enzymology, 233, 346–363.
Liu, J., & Mori, A. (1993). Monoamine metabolism provides an antioxidant defense in the brain against oxidant-and free radical-induced damage. Archives of Biochemistry and Biophysics, 302, 118–127.
Liu, J., & Mori, A. (1994). Involvement of reactive oxygen species in emotional stress: A hypothesis based on the immobilization stress-induced oxidative damage and antioxidant defense changes in rat brain, and the effect of antioxidant treatment with reduced glutathione. International Journal of Stress Management, 1, 249–263.
Liu, J., Wang, X., & Mori, A. (1994). Immobilization stress-induced antioxidant defense changes in rat plasma: Effect of treatment with reduced glutathione. International Journal of Biochemistry, 26, 511–517.
Liu, J., Wang, X., Shigenaga, M. K., Yeo, H. C., Mori, A., & Ames, B. N. (1996a). Immobilization stress causes oxidative damage to lipid, protein, and DNA in the brain of rats. FASEB Journal, 10, 1532–1538.
Liu, J., Shigenaga, M. K., Mori, A., & Ames, B. N. (1996b). Free radicals and neurodegenerative diseases: Stress and oxidative damage. In L. Packer, M. Hiramatsu and T. Yoshikawa (Eds.), Free radicals and brain physiology and disorders (pp. 403–437). New York: Academic Press.
Lowy, M. T., Gault, L., & Yamamoto, B. K. (1993). Adrenalectomy attenuates stress-induced elevations in extracellular glutamate concentrations in the hippocampus. Journal of Neurochemistry, 61, 1957–1960.
Lowy, M. T., Wittenberg, L., & Novotney, S. (1994). Adrenalectomy attenuates kainic acid-induced spectrin proteolysis and heat shock protein 70 induction in hippocampus and cortex. Journal of Neurochemistry, 63, 886–894.
McNeill, T. H., Masters, J. N., & Finch, C. E. (1991). Effect of chronic adrenalectomy on neuron loss and distribution of sulfated glycoprotein-2 in the dentate gyrus of prepubertal rats. Experimental Neurology, 111, 140–144.
Moghaddam, B. (1993). Stress preferentially increases extraneuronal levels of excitatory amino acids in the prefrontal cortex: comparison to hippocampus and basal ganglia. Journal of Neurochemistry, 60, 1650–1657.
Mugridge, K. G., Perretti, M., Becherucci, C., & Parente, L. (1991). Persistent effects of interleukin-1 on smooth muscle preparations from adrenalectomized rats: implications for increased phospholipase-A2 activity via stimulation of 5-lipoxygenase. Journal of Pharmacology & Experimental Therapy, 256, 29–37.
Munck, A., Guyne, P., & Holbrook, N. (1984). Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocrine Review, 5, 25–44.
Pacak, K., Yadid, G. J., Lenders, J. W., Kopin, I. J., & Goldstein, D. S. (1993). In viv hypothalamic release and synthesis of catecholamines in spontaneously hypertensive rats. Hypertension, 22, 467–478.
Park, J.-Y. K., Shigenaga, M. K., & Ames, B. N. (1996). Induction of cytochrome P4501A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin or indolo(3,2-b)carbazole is associated with oxidative DNA damage. Proceedings of the National Academy of Science USA, 93, 2322–2327.
Platner, W. S. (1961). The effect of stress on the aging process. Missouri Medicine, 58, 373–376.
Roth, R. H., Tam, S. Y., Ida, Y., Yang, J. X., & Deutch, A. Y. (1988). Stress and the mesocorticolimbic dopamine systems. Annals of NewYork Academy of Science, 537, 138–147.
Rowe, B., Ronzio, R. A., & Wellner, V. P. (1970). Glutamine synthetase (Sheep brain). Methods in Enzymology, 17a, 900–910.
Roy, E. J., Lynn, D. M., & Bemm, C. W. (1990). Individual variations in hippocampal dentate degeneration following adrenalectomy. Behavioral and Neural Biology, 54, 330–336.
Sapolsky, R. M., Stein, B. B., & Armanini, M. P. (1991). Long-term adrenalectomy causes loss of dentate gyrus and pyramidal neurons in the adult hippocampus. Experimental Neurology, 114, 246–249.
Shigenaga, K. M., Aboujaoude, E. N., Chen, Q., & Ames, B. N. (1994). Assays of oxidative DNA damage biomaker 8-oxo-2′-deoxyguanosine and 8-oxoguanine in nuclear DNA and biological fluids by high performance liquid chromatography with electrochemical detection. Methods in Enzymology, 234, 16–33.
Sloviter, R. S., Valiquette, G., Abrams, G. M., Ronk, E. C., Sollas, A. L., Paul, L. A., & Neubort, S. (1989). Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy. Science, 243, 535–538.
Smith, C. D., Carney, J. M., Starke, R. P., Oliver, C. N., Stadtman, E. R., Floyd, R. A., & Markesbery, W. R. (1991). Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proceedings of the National Academy of Science USA, 88, 10540–10543.
Solito, E., & Parente, L. (1989). Modulation of phospholipase A2 activity in human fibroblasts. British Journal of Pharmacology, 96, 656–660.
Stadtman, E. R. (1992). Protein oxidation and aging. Science, 257, 1220–1224.
Stein, B. A., & Sapolsky, R. M. (1988). Chemical adrenalectomy reduces hippocampal damage induced by kainic acid. Brain Research, 473, 175–180.
Stein, B. B., & Sapolsky, R. M. (1992). Stress, glucocorticoids, and aging. Aging (Milano), 4, 197–210.
Tanaka, M., Kohno, Y., Nakagawa, R., Ida, Y., Iimori, K., Hoaki, Y., Tsuda, A., & Nagasaki, N. (1982a). Naloxone enhances stress-induced increases in noradrenaline turnover in specific brain regions in rats. Life Science, 30, 1663–1669.
Tanaka, M., Kohno, Y., Nakagawa, R., Ida, Y., Takeda, S., & Nagasaki, N. (1982b). Time-related differences in noradrenaline turnover in rat brain regions by stress. Pharmacology, Biochemistry & Behavior, 16, 315–319.
Tanaka, M., Y., K., Nakagawa, R., Ida, Y., Takeda, S., Nagasaki, N., & Noda, Y. (1983). Regional characteristics of stress-induced increases in brain noradrealine release in rats. Pharmacology Biochemistry & Behavior, 19, 543–547.
Vetrugno, G. C., Lachuer, J., Perego, C., Miranda, E., De Simoni, M. G., & Tappaz, M. (1993). Lack of glucocorticoids sustains the stress-induced release of noradrenaline in the anterior hypothalamus. Neuroendocrinology, 57, 835–842.
Weidenfeld, J., Lysy, J., & Shohami, E. (1987). The effect of dexamethasone on prostaglandin synthesis in various brain areas of the rats. Journal of Neurochemistry, 48, 1351–1356.
Weininger, O. (1956). The effect of early experience on behavior and growth characteristics. Journal Comprehensive Physiology and Psychology, 49, 1–9.
Weiss, J., Goodman, P., Losito, B., Corrigan, S., Charry, J., & Bailey, W. (1981). Behavioral depression produced by an uncontrollable stressor: Relationship to norepinephrine, dopamine, and serotonin levels in various regions of rat brain. Brain Research Review, 3, 167–205.
Wiechelman, K., Braun, R., & Fitzpatrick, J. (1988). Investigation of the bicinchoninic acid protein assay: Identification of the groups responsible for color formation. Analytical Biochemistry, 175, 231–237.
Yeo, H. C., Helbock, H. J., Chyu, D. W., & Ames, B. N. (1994). Assay of malondehyde in biological fluids by gas chromatography-mass spectrometry. Analytical Biochemistry, 220, 391–396.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Liu, J., Yokoi, I., Doniger, S.J. et al. Adrenalectomy Causes Oxidative Damage and Monoamine Increase in the Brain of Rats and Enhances Immobilization Stress-Induced Oxidative Damage and Neurotransmitter Changes. International Journal of Stress Management 5, 39–56 (1998). https://doi.org/10.1023/A:1022954820224
Issue Date:
DOI: https://doi.org/10.1023/A:1022954820224