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Chronic combined stress induces selective and long-lasting inflammatory response evoked by changes in corticosterone accumulation and signaling in rat hippocampus

Metabolic Brain Disease volume 31, pages 445–454 (2016)Cite this article

Abstract

Hippocampus is believed to be selectively vulnerable to stress. We hypothesized that this phenomenon may be mediated by relatively high vulnerability to neuroinflammation related to impairments of local glucocorticoid metabolism and signaling. We have evaluated inflammatory responses induced by acute or chronic combined stress in the cerebral cortex and hippocampus as well as circulating and brain corticosterone (CS) levels as well as expression of corticosterone target genes. The hippocampus showed higher stress-induced expression of the proinflammatory cytokine IL-1β as compared to the cerebral cortex. A month after the termination of the chronic stress, IL-1β mRNA in the cerebral cortex reached control level, while in the hippocampus it remained significantly increased. Under chronic stress, the maladaptive inflammatory response in hippocampus was accompanied by a significant increase in local CS levels, as compared to cerebral cortex. Under acute stress, the increased CS level induced changes in CS-regulated genes expression (CRF and IGF1), while this phenomenon was not observed after chronic stress. Thus, the hippocampus appears to be more vulnerable to stress-induced inflammation as compared to the neocortex and demonstrates persistent inflammatory response induced by chronic stress. Stress-induced maladaptive inflammatory response is associated with a selective increase in hippocampal CS accumulation and changes in CS signaling.

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Acknowledgments

The authors would like to thank Natalia Lazareva and Natalia Stepanicheva for excellent technical assistance as well as Alexander Yakovlev and Mikhail Onufriev for their help and valuable advice.

This study was supported by the Russian Science Foundation grant # 14-25-00136.

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    Authors and Affiliations

    1. Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia

      Aleksey Piskunov, Mikhail Stepanichev, Anna Tishkina, Margarita Novikova, Irina Levshina & Natalia Gulyaeva

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    1. Aleksey Piskunov
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    2. Mikhail Stepanichev
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    3. Anna Tishkina
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    6. Natalia Gulyaeva
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    Correspondence to Natalia Gulyaeva.

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    Aleksey Piskunov and Mikhail Stepanichev equally contributed to this study.

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    Piskunov, A., Stepanichev, M., Tishkina, A. et al. Chronic combined stress induces selective and long-lasting inflammatory response evoked by changes in corticosterone accumulation and signaling in rat hippocampus. Metab Brain Dis 31, 445–454 (2016). https://doi.org/10.1007/s11011-015-9785-7

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    • DOI: https://doi.org/10.1007/s11011-015-9785-7

    Keywords

    • Neuroinflammation
    • Hippocampus
    • Stress
    • Glucocorticoid
    • Corticosterone