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Region-specific changes in activities of cell death-related proteases and nitric oxide metabolism in rat brain in a chronic unpredictable stress model

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Abstract

Effects of a chronic combined unpredictable stress on activities of two cell death-related proteases, calpain and cathepsin B, were studied along with indices of nitrergic system in rat brain structures. Male Wistar rats were subjected to a 2-week-long combined stress (combination of unpaired flash light and moderate footshock associated with a white noise session). Stress resulted in a significant loss in the body and thymus weight and increased defecation in the open field test, though neither motor and exploratory activity, nor plasma corticosterone differed from the respective control levels. Decreased calpain activity and increased cathepsin B activity were demonstrated in the hippocampus of stressed rats (previously we have shown that caspase-3 activity was significantly suppressed in the brain of rats subjected to same type of stress). A significant reduction in the number of NOS-containing neurons was accompanied by a chronic stressinduced decline in NOS activity in the neocortex. Similar changes were observed in the hippocampus. However, levels of NO metabolites were elevated in both structures. Thus, stress-induced structural modifications in the brain may be mediated by disturbances in the nitrergic system and increased lysosomal proteolysis.

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Acknowledgments

This study was supported by a grant of Russian Academy of Sciences Presidium program “Fundamental Sciences for Medicine” and a grant of Division of Physiology and Fundamental Medicine Russian Academy of Sciences program “Integrative Physiology”.

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The authors declare that they have no conflicts of interest.

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  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

    Anna Tishkina, Alexey Rukhlenko, Mikhail Stepanichev, Irina Levshina, Natalia Pasikova, Mikhail Onufriev, Yulia Moiseeva, Alexey Piskunov & Natalia Gulyaeva

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  1. Anna Tishkina
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  2. Alexey Rukhlenko
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  3. Mikhail Stepanichev
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  4. Irina Levshina
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  5. Natalia Pasikova
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  6. Mikhail Onufriev
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  7. Yulia Moiseeva
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  9. Natalia Gulyaeva
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Correspondence to Natalia Gulyaeva.

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Tishkina, A., Rukhlenko, A., Stepanichev, M. et al. Region-specific changes in activities of cell death-related proteases and nitric oxide metabolism in rat brain in a chronic unpredictable stress model. Metab Brain Dis 27, 431–441 (2012). https://doi.org/10.1007/s11011-012-9328-4

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