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Effects of Chronic Neurogenic Stress on Behavior of Rats and Contents of Sphingolipids in Their Brain and Peripheral Tissues

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Neurophysiology Aims and scope

We studied the contents of ceramide and sphingomyelin (SM) in the hippocampus, neocortex, and peripheral tissues of rats and the behavior characteristics of these animals in the open field at different times after the induction of chronic neurogenic stress. The experiments were carried out on young Wistar rats weighing 180–220 g, with a mean level of behavioral mobility. Within the poststress period, animals demonstrated significant suppression of manifestations of motor and orientational/research activities, and intensification of autonomic manifestations of fear and anxiety (with a delay of leaving the field center). One day after termination of stressing, the content of ceramide in the hippocampus increased against the background of a drop in the SM level, but this did not occur in the neocortex, liver, and blood serum. The contents of phosphatidylcholine and phosphatidylethanolamine in the brains of animals exposed to stress did not change. Eight days after stressing, the level of ceramide in the brain structures and blood serum was significantly higher than in the control. These data suggest that the action of chronic neurogenic stress leads to activation of metabolism of sphingolipids and intensification of production of ceramide in the brain and blood serum. Accumulation of ceramide in the serum within a remote period after termination of the action of stress can serve as a marker of the stable development of a state of emotional tension accompanied by typical signs of depression-like behavior.

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References

  1. B. Ramstedt and J. P. Slotte, “Sphingolipids and the formation of sterol-enriched ordered membrane domains,” Biochim. Biophys. Acta, 1758, No. 12, 1945-1956 (2006).

    Article  CAS  PubMed  Google Scholar 

  2. T. G. Oliveira, R. B. Chan, F. V. Bravo, et al., “The impact of chronic stress on the rat brain lipidome,” Mol. Psychiat. (2015), doi:10.1038/mp.2015.14.

  3. E. Gulbins, M. Palmada, M. Reichel, et al., “Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs,” Nat. Med., 19, No. 7, 934-938 (2013).

    Article  CAS  PubMed  Google Scholar 

  4. V. Krishnan and E. J. Nestler, “The molecular neurobiology of depression,” Nature, 455, No. 7215, 894-902 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. L. Santarelli, M. Saxe, C. Gross, et al., “Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants,” Science, 301, No. 5634, 805-809 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. J. Kornhuber, J. Muehlbacher, S. Trapp, et al., “Identification of novel functional inhibitors of acid sphingomyelinase,” PloS One, 6, No. 8, e23852 (2011), doi:10.1371/journal.pone.0023852.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. J. Kornhuber, P. Tripal, M. Reichel, et al., “Functional Inhibitors of acid sphingomyelinase (FIASMAs): a novel pharmacological group of drugs with broad clinical applications,” Cell. Physiol. Biochem., 26, No. 1, 9-20 (2010).

    Article  CAS  PubMed  Google Scholar 

  8. H.-C. Su, C.-T. Ma, C.-F. Lin, et al., “The acid sphingomyelinase inhibitors block interferon-α-induced serotonin uptake via a COX-2/Akt/ERK/STAT-dependent pathway in T cells,” Int. Immunopharmacol., 11, No. 11, 1823-1831 (2011).

    Article  CAS  PubMed  Google Scholar 

  9. Z. Nahas, Y. Jiang, Y. H. Zeidan, et al., “Anti-ceramidase LCL385 acutely reduces BCL-2 expression in the hippocampus but is not associated with an increase of learned helplessness in rats,” Behav. Brain Res., 197, No. 1, 41-44 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. G. Anderson and M. Maes, “Reconceptualizing adult neurogenesis: role for sphingosine-1-phosphate and fibroblast growth factor-1 in co-ordinating astrocyteneuronal precursor interactions,” CNS Neurol. Disord. Drug Targets, 13, No. 1, 126-136 (2014).

    Article  CAS  PubMed  Google Scholar 

  11. S. Jang, S. H. Suh, H. S. Yoo, et al., “Changes in iNOS, GFAP and NR1 expression in various brain regions and elevation of sphingosine-1-phosphate in serum after immobilized stress,” Neurochem. Res., 33, No. 5, 842-851 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. N. Akahoshi, Y. Ishizaki, H. Yasuda, et al., “Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2,” Epilepsy Behav., 22, No. 4, 659-665 (2011).

    Article  PubMed  Google Scholar 

  13. J. Bureš, O. Burešova, and J. P. Huston, Techniques and Basic Experiments for the Study of Brain and Behavior [in Russian],Vyssh. Shkola, Moscow (1991).

  14. V. M. Shevereva, “Pecularities of the formation and reversibility of emotional disorders in rats at neurogenic stress,” Neirofiziologya/Neurophysiology, 35, No. 2, 147-158 (2003).

    Google Scholar 

  15. E. G. Bligh and W. J. Dyer, “A rapid method of total lipid extraction and purification,” Can. J. Biochem. Physiol., 37, No. 8, 911-917 (1959).

    Article  CAS  PubMed  Google Scholar 

  16. G. R. Bartlett, “Phosphorus assay in column chromatography,” J. Biol. Chem., 234, No. 3, 466-468 (1959).

    CAS  PubMed  Google Scholar 

  17. S. Sathishkumar, B. Boyanovsky, A. Karakashian, et al., “Elevated sphingomyelinase activity and ceramide concentration in serum of patients undergoing high dose spatially fractionated radiation treatment: implications for endothelial apoptosis,” Cancer Biol. Ther., 4, No. 9, 979-986 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. N. N. Dubrovina, “Extinction of fear memory in animal models of depression,” Usp. Fiziol. Nauk, 42, No. 1, 53-66 (2011).

    CAS  PubMed  Google Scholar 

  19. D. F. Avgustinovich, O. V. Alekseyenko, I. V. Bakshtanovskaya, et al., “Dynamic changes in serotonergic and dopaminergic activity in the brain during the development of anxiety-related depression: An experimental study,” Usp. Fiziol. Nauk, 35, No. 4, 19-40 (2004).

    CAS  PubMed  Google Scholar 

  20. V. M. Sheveryova, “ Effect of chronic emotional stress on the behavior of rats with different levels of motor activity in the “open field” test,” Fiziol. Zh., 51, No. 1, 94-105 (2011).

    Google Scholar 

  21. V. N. Semagin, A. V. Zukhar’, and M. A. Kulikov, Type of the Nervous System: Resistivity to Stress and the Reproduction Function, Nauka, Moscow (1988).

  22. R. Faria, M. M. Santana, C. A. Aveleira, et al., “Alterations in phospholipidomic profile in the brain of mouse model of depression induced by chronic unpredictable stress,” Neuroscience, 273, 1-11 (2014).

    Article  CAS  PubMed  Google Scholar 

  23. A. M. Troen, W. H. Chao, N. A. Crivello, et al., “Cognitive impairment in folate-deficient rats corresponds to depleted brain phosphatidylcholine and is prevented by dietary methionine without lowering plasma homocysteine,” J. Nutr., 138, No. 12, 2502-2509 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. T. M. Michel, D. Pülschen, and J. Thome, “The role of oxidative stress in depressive disorders,” Current Pharm. Des., 18, No. 36, 5890-5899 (2012).

    Article  CAS  Google Scholar 

  25. A. H. Miller, “Depression and immunity: a role for T cells?” Brain, Behav., Immunol., 24, No. 1, 1-8 (2010).

    CAS  Google Scholar 

  26. D. Wheeler, E. Knapp, V. V. Bandaru, et al., “Tumor necrosis factor-alpha-induced neutral sphingomyelinase-2 modulates synaptic plasticity by controlling the membrane insertion of NMDA receptors,” J. Neurochem., 109, No. 5, 1237-1249 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. N. Sanvicens and T. G. Cotter, “Ceramide is the key mediator of oxidative stress-induced apoptosis in retinal photoreceptor cells,” J. Neurochem., 98, No. 5, 1432-1444 (2006).

    Article  CAS  PubMed  Google Scholar 

  28. N. A. Babenko, L. K. Hassouneh, V. S. Kharchenko, et al., “Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells,” Age, 34, No. 4, 905-915 (2012).

    Article  CAS  PubMed  Google Scholar 

  29. N. A. Babenko and E. G. Shakhova, “Long-term food restriction prevents aging-associated sphingolipid turnover dysregulation in the brain,” Arch. Gerontol., Geriat., 58, No. 3, 420-426 (2014).

    Article  Google Scholar 

  30. N. A. Babenko and O. G. Shakhova, “Effect of an inhibitor of sphingomyelinases, N-acetylcysteine, on cognitive functions in old rats,” Neurophysiology, 46, No. 2, 180-182 (2014).

    Article  CAS  Google Scholar 

  31. R. W. Jenkins, D. Canals, and Y. A. Hannun, “Roles and regulation of secretory and lysosomal acid sphingomyelinase,” Cell. Signal., 21, No. 6, 836-846 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. S. M. Hammad, J. P. Truman, M. Al Gadban, et al., “Altered blood sphingolipidomics and elevated plasma inflammatory cytokines in combat veterans with posttraumatic stress disorder,” Neurobiol. Lipids, 10, 2 (2012).

    PubMed  Google Scholar 

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Babenko, N.A., Shevereva, V.M. & Gar’kavenko, V.V. Effects of Chronic Neurogenic Stress on Behavior of Rats and Contents of Sphingolipids in Their Brain and Peripheral Tissues. Neurophysiology 48, 346–353 (2016). https://doi.org/10.1007/s11062-017-9608-z

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  • DOI: https://doi.org/10.1007/s11062-017-9608-z

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