Skip to main content
SpringerLink
Log in

Brain Oxidative Damage Following Acute Immobilization and Mild Emotional Stress

  • Published:
International Journal of Stress Management

Abstract

We studied the role of free radicals on brain oxidative damage in rats after acute immobilization stress (restraint) and mild emotional stress (handling). To investigate brain oxidative damage, CuZn and Mn dependent superoxide dismutase (CuZn SOD, Mn SOD) activities, lipid peroxidation (TBARs), Na + K + ATPase activity, protein carbonyl (PrC), and reduced and oxidized glutathione (GSH, GSSG) levels were measured in the cerebral cortex (CTX), hippocampus (HIP), and striatum (ST) of the animals after the two different stress stimuli. Because stress produces abnormalities in the hypothalamic-pituitary-adrenal axis, the intensity of the two stress conditions were measured by plasmatic corticosteroid (COR) levels: particularly, COR levels doubled in handled rats and increased 15-fold in restrained animals. The SOD activities increased in CTX and decreased in HIP of the handled rats, while in ST a significant decrease in handled animals but an increase in restrained animals occurred. TBARs, GSH, and GSSG levels remained unchanged, while an index of glutathione redox decreased significantly in ST of handled animals and in CTX of restrained ones. Na + K + ATPase activity increased significantly in the HIP and ST of both groups of stressed rats. The stress induced a remarkable increase in PrC levels in all studied cerebral areas. These findings provide evidence to support the idea that stress produces oxidants but that the oxidative damage in stress differs in cerebral areas and could contribute to the degenerative mechanism of aging.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Anderson, M. (1985). Handbook of Methods for Oxygen Radical Research. CRC Press.

  • Axelrod, J., & Reimsine, T. D. (1984). Stress hormones: Their interaction and regulation. Science, 224, 452–459.

    Google Scholar 

  • Bolting, H. L., Simmon, K. A., & Hawkins, N. M. (1961). Studies on sodium-potassium-activated adenosine triphosphate. Archives of Biochemistry and Biophysics, 95, 416–423.

    Google Scholar 

  • Bolzan, A. D., Braun, A. O., Goya, R. G., & Bianchi, S. M. (1995). Hormonal modulation of antioxidant enzyme activities in young and old rats. Experimental Gerontology, 30, 169–175.

    Google Scholar 

  • Cholst, S. (1996). Cancer and stress. Medical Hypotheses, 46, 101–106.

    Google Scholar 

  • Chou, T. C., Lin, W. J., & Sapolsky, R. M. (1994). Glucocorticoids increase extracellular [3H] D-aspartate overflow in hippocampal cultures during cyanide-induced ischemia. Brain Research, 654, 8–14.

    Google Scholar 

  • Climent, I., Tsai, L., & Levine, R. L. (1989). Derivatization of gamma-glutamyl semialdehyde residues in oxidized proteins by fluoresceinamine. Analytical Biochemistry, 182, 226–232.

    Google Scholar 

  • Davies, M. (1970). Effects of interstimulus interval length and variability on startle-response habituation in the rat. Journal of Comprehensive Physiological Psychology, 72, 177–192.

    Google Scholar 

  • De Boer, S. F., Slangen, J. L., & Van der Gugten, J. (1988). Adaptation of plasma catecholamine and corticosterone responses to short-term repeated noise stress in rats. Physiological Behavioral, 44, 273–280.

    Google Scholar 

  • De Turck, K., & Vogel, W. H. (1980). Factors influencing plasma catecholamine levels in rats during immobilization. Pharmacology Biochemistry and Behavior, 13, 129–131.

    Google Scholar 

  • Flohé, L. & Otting, F. (1984). Superoxide dismutase assays. Methods in Enzymology, 105, 93–104.

    Google Scholar 

  • Gilbert, J. C., & Sawas, A. H. (1983). ATPase activities and lipid peroxidation in rat cerebral cortex synaptosomes. Archives of International Pharmacodynamics, 263, 189–196.

    Google Scholar 

  • Gilad, G. M., & Gilad, V. H. (1996). Brain polyamine stress response: Recurrence after repetitive stressor and inhibition by lithium. Journal of Neurochemistry, 67, 1992–1996.

    Google Scholar 

  • Godfraind, T., Koch, M. C., & Verbeke, N. (1974). The action of EGTA on the catecholamines stimulation of rat brain Na+-K+ ATPase. Biochemical Pharmacology, 23, 3505–3511.

    Google Scholar 

  • Groves, P. M. & Thompson, R. F. (1970). Habituation: A dual-process theory. Psychological Review, 77, 419–450.

    Google Scholar 

  • Gupta, A., & Hasan, M. (1988). Age-related changes in lipid profiles and lipid peroxidation in the CNS following restraint stress. Indian Journal of Medical Research, 87, 624–630.

    Google Scholar 

  • Kawabata, A., & Hata, T. (1993). Possible involvement of oxygen-derived free radicals in abnormal hemostasis by Sart stress (repeated cold stress) in laboratory animals. Thrombosis Research, 72, 321–331.

    Google Scholar 

  • Kovacheva-Ivanova, S., Bakalova, R., Kagan, V., & Georgriev, G. (1992). Activation of lipid peroxidation and changes in vitamin E contents in the lungs under oxidative stress. Biulleten Eksperimentalnoi Biologii Meditsiny, 113, 132–134.

    Google Scholar 

  • Kovacheva-Ivanova, S., Bakalova, R., & Ribarov, S. R. (1994). Immobilisation stress enhances lipid peroxidation in rat lungs. General Physiology and Biophysics, 13, 469–482.

    Google Scholar 

  • Kovachich, G. B., & Mishra, O. P. (1981). Partial inactivation of Na+,K+-ATPase in cortical brain slices incubated in normal Krebs-Ringer phosphate medium at 1 and 10 atm oxygen pressure. Journal of Neurochemistry, 36, 333–335.

    Google Scholar 

  • Kukreja, R. C., Weaver, A. B., & Hess, M. L. (1990). Sarcolemmal Na+K+ ATPase: Inactivation by neutrophil-derived free radicals and oxidants. American Journal of Physiology, 259, 1330–1336.

    Google Scholar 

  • Kvetnansky, R., Kopin, I. J., & Saavedra, J. M. (1978). Changes in epinephrine in individual hypothalamic nuclei after immobilization stress. Brain Research, 155, 387–390.

    Google Scholar 

  • Kvetnansky, R., McCarty, R., Thoa, N. B., Lake, C. R., & Kopin, I. J. (1979). Sympatho-adrenal responses of spontaneously hypertensive rats in immobilization stress. American Journal of Physiology, 236, 457–462.

    Google Scholar 

  • Landfield, P. W., Waymire, J., & Lynch, G. (1978). Hippocampal aging and adrenocorticoids: A quantitative correlation. Science, 202, 1098–1102.

    Google Scholar 

  • Levine, R. L., Garland, D., Oliver, C. N., Amici, A., Climent, I., Lenz, A. G., Ahn, B. W., Shaltiel, S., & Stadtman, E. R. (1990). Determination of carbonyl content in oxidatively modified proteins. Methods in Enzymology, 186, 464–478.

    Google Scholar 

  • 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 defence changes in rat brain and the effect of antioxidant treatment with reduced glutathione. International Journal of Stress Management, 1, 249–263.

    Google Scholar 

  • Liu, J., Wang, X., & Mori, A. (1994). Immobilisation stress-induced antioxidants defence changes in rat plasma: Effect of treatment with reduced glutathione. International Journal of Biochemistry, 26, 611–617.

    Google Scholar 

  • Liu, J., Wang, X., Shigenaga, M. K., Yeo, H. C., Mori, A., & Ames, B. (1996a). Immobilisation stress causes oxidative damage to lipid, protein & DNA in the brain rats. The FASEB Journal, 10, 1532–1538.

    Google Scholar 

  • Liu, J., Shigenada, M. K., Mori, A., & Ames, B. (1996b). Free radicals and neurodegenerative diseases: Stress and oxidative damage. In Free Radicals in Brain Physiology and Disorders (pp. 403–437). New York: Academic Press.

    Google Scholar 

  • Liu, J., Wang, X., & Mori, A. (1996c). Antioxidant mechanism of the antistress effects of Yi-Zhi-Yi-Shou, an extract prepared from a prescription of traditional Chinese medicines. In A. Mori, & T. Satoab (Eds.), Molecular Aspects of Asian Medicines. New York: PJD Publications Limited.

    Google Scholar 

  • Lowry, O. H., Rosenbrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with Folin phenol reagent. Journal of Biological Chemistry, 193, 265–275.

    Google Scholar 

  • McCarty, R., & Kopin, J. J. (1978). Alteration in plasma catecholamine and behavior during acute stress in spontaneously hypertensive and W-K-normotensive rats. Live Science, 22, 997–1006.

    Google Scholar 

  • Meaney, M. J., Aitken, D. H., Bhatnagar, S., & Sapolsky, R. M. (1991). Postnatal handling attenuates certain neuroendocrine, anatomical, and cognitive dysfunction associated with aging in female rats. Neurobiology of Aging, 12, 31–38.

    Google Scholar 

  • Mennini, T., Gobbi, M., Perin, L., & Salmona, M. (1988). Chloride Channels and Their Modulation by Neurotrasmitters and Drugs. New York: Raven Press.

    Google Scholar 

  • Natelson, B. (1983). Stress, predisposition, and the onset of serious disease: Implication about psychosomatic etiology. Neuroscience and Behavioral Review, 7, 511–527.

    Google Scholar 

  • Natelson, B. H., Creighton, D., McCarty, R., Tapp, W. N., Pitman, D., & Ottenweller, J. E. (1987). Adrenal hormonal indices of stress in laboratory rats. Physiological Behavioral, 39, 117–125.

    Google Scholar 

  • Ohkawa, H., Ohishi, N., & Yagi, K. (1951). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95, 351–358.

    Google Scholar 

  • Oliver, C. N., Ahn, B. W., Moerman, E. J., Goldstein, S., & Stadtman, E. R. (1987). Age-related changes in oxidized proteins. Journal of Biological Chemistry, 262, 5488–5491.

    Google Scholar 

  • Pacifici, R. E., & Davies, K. J. A. (1990). Protein degradation as an index of oxidative stress. Methods in Enzymology, 186, 485–502.

    Google Scholar 

  • Paré, W. S. (1965). The effect of chronic environmental stress on premature aging in the rat. Journal of Gerontology, 20, 78–84.

    Google Scholar 

  • Plotsky, P., Bruhn, T., & Vale, W. (1985). Evidence for multifactors regulation of the adrenocorticotropin secretory response to hemodynamic stimuli. Endocrinology, 116, 633–639.

    Google Scholar 

  • Saavedra, J. M., Kvetnansky, R., & Kopin, I. J. (1979). Adrenaline, noradrenaline and dopamine levels in specific brain stem areas of acutely immobilized rats. Brain Research, 160, 271–280.

    Google Scholar 

  • Sapolsky, R. M. A. (1985). Mechanism for glucocorticoid toxicity in the hippocampus: Increased neuronal vulnerability to metabolic insults. Journal of Neuroscience, 5, 1228–1232.

    Google Scholar 

  • Schaefer, A., Seregi, A., & Komlos, M. (1974). Ascorbic acid-like effect of the soluble fraction of rat brain on adenosine triphosphatase and its relation to catecholamines and chelating agents. Biochemical Pharmacology, 23, 2257–2271.

    Google Scholar 

  • Seredenin, S. B., Badyshtov, B. A., & Ergov, D. I. (1992). Contents of lipid peroxidation products in inbred mice with different types of emotional stress reaction. Biulleten Eksperimentalnoi Biologii Meditsiny, 108, 46–48.

    Google Scholar 

  • Shvets, V. N., & Davydov, V. V. (1993). State of induced lipid peroxidation in the heart of mature and aged rats under stress. Ukrainskij Biokhimiceskij Zhurnal, 65, 91–96.

    Google Scholar 

  • Siems, W., Mueller, M., & Garbe, S. (1987). Damage of erithrocytes by activated oxygen generated in hypoxic rat liver. Free Radical Research Communications, 4, 31–39.

    Google Scholar 

  • Smith, C. D., Carney, J. M., Starke-Reed, P. E., 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's disease. Proceedings of National Academy of Sciences of the United States of America, 88, 10540–10543.

    Google Scholar 

  • Sosnovsky, A. S., Tsvetkova, M. A., Uzunnova, P. I., Glbova, T. D., Peneva, V. I., Sokolova, T. I., Ribarov, S. R., & Nikolov, N. A. (1992). Lipid peroxidation in emotional stress in rats: correlation with parameters of open field behavior. Biulleten Eksperimentalnoi Biologii Meditsiny, 113, 19–21.

    Google Scholar 

  • Sosnovsky, A. S., Balashova, T. S., & Kubatiev, A. A. (1993). Behavioral cluster and the rat brain antioxidants enzymes in immobilisation stress. Neurosciences-Japan, 19, 141–149.

    Google Scholar 

  • Stadtman, E. R. (1992). Protein oxidation and aging. Science, 257, 1220–1224.

    Google Scholar 

  • Starke-Reed, P. E., & Oliver, C. N. (1989). Protein oxidation and proteolysis during aging and oxidative stress. Archives of Biochemistry and Biophysics, 275, 559–567.

    Google Scholar 

  • Thompson, R. F., Berry, S. D., Rinaldi, P. C., & Berger, T. W. (1979). Habituation and the orienting reflex: The dual process theory revised. In H. D. Kimmel, E. H. Van Olst, & J. F. Orlebeke (Eds.), The Orienting Reflex in Humans (pp. 21–61). Hillsdale, NJ: Lawrence Erlbaum Associates.

    Google Scholar 

  • Tombaugh, G. C., Yang, S. H., Swanson, R. A., & Sapolsky, R. M. (1992). Glucocorticoids exacerbate hypoxic and hypoglycemic hippocampal injury in vitro: Biochemical correlates and a role for astrocytes. Journal of Neurochemistry, 59, 137–146.

    Google Scholar 

  • Yoshimura, K. (1973). Activation of Na+-K+ activated ATPase in rat brain by catecholamine. Journal of Biochemistry, 74, 389–391.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmacology, University of Pavia, Pavia, Italy

    Fulvio Marzatico, Laura Bertorelli, Orietta Pansarasa & Paola Guallini

  2. Institute of Physiology, University of Modena, Modena, Italy

    Carla Torri & Giuseppe Biagini

Authors
  1. Fulvio Marzatico
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Bertorelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Orietta Pansarasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paola Guallini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carla Torri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giuseppe Biagini
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marzatico, F., Bertorelli, L., Pansarasa, O. et al. Brain Oxidative Damage Following Acute Immobilization and Mild Emotional Stress. International Journal of Stress Management 5, 223–236 (1998). https://doi.org/10.1023/A:1022969828885

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022969828885

Search

Navigation