Bulletin of Experimental Biology and Medicine

, Volume 164, Issue 4, pp 425–429 | Cite as

Changes in Activity of Cysteine Cathepsins B and L in Brain Structures of Mice with Aggressive and Depressive-Like Behavior Formed under Conditions of Social Stress

  • S. Ya. Zhanaeva
  • A. A. Rogozhnikova
  • E. L. Alperina
  • M. M. Gevorgyan
  • G. V. Idov

We studied activity of lysosomal cysteine proteases, cathepsins B and L, in brain structures (frontal cortex, caudate nucleus, hippocampus, and hypothalamus) of C57Bl/6J mice with aggressive and depressive-like behavior formed under conditions of chronic social stress (repeated experience of victories and defeats within 20 days). Mice with depressive-like behavior showed increased activity of cathepsin В in the hypothalamus and nucleus caudatus and increased activity of cathepsin L in the hippocampus compared to control animals not subjected to agonistic confrontations. In mice with aggressive behavior, protease activity in the studied brain structures was not changed. In 4 h after immune system activation with LPS (250 μg/kg), cathepsin L activity in the hippocampus of control mice increased in comparison with mice receiving saline. In contrast to control animals, LPS caused a decrease in activity of the enzyme in the caudate nucleus and frontal cortex of aggressive mice and in the hippocampus of mice with depressive-like behavior.

Key Words

aggressive and depressive-like behavior chronic social stress brain structures cathepsins B and L 


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  1. 1.
    Avgustinovich DF, Marenina MK, Zhanaeva SY, Tenditnik MV, Katokhin AV, Pavlov KS, Sivkov AY, Vishnivetskaya GB, Lvova MN, Tolstikova TG, Mordvinov VA. Combined effects of social stress and liver fluke infection in a mouse model. Brain Behav. Immun. 2016;53:262-272.CrossRefPubMedGoogle Scholar
  2. 2.
    Brown GC, Vilalta A. How microglia kill neurons. Brain Res. 2015;1628(Pt B):288-297.CrossRefPubMedGoogle Scholar
  3. 3.
    Czibere L, Baur LA, Wittmann A, Gemmeke K, Steiner A, Weber P, Pütz B, Ahmad N, Bunck M, Graf C, Widner R, Kühne C, Panhuysen M, Hambsch B, Rieder G, Reinheckel T, Peters C, Holsboer F, Landgraf R, Deussing JM. Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice. PLoS One. 2011;6(8):e23604. doi: Scholar
  4. 4.
    Hook V, Funkelstein L, Wegrzyn J, Bark S, Kindy M, Hook G. Cysteine Cathepsins in the secretory vesicle produce active peptides: Cathepsin L generates peptide neurotransmitters and cathepsin B produces beta-amyloid of Alzheimer’s disease. Biochim. Biophys. Acta. 2012;1824(1):89-104.CrossRefPubMedGoogle Scholar
  5. 5.
    Karanges EA, Kashem MA, Sarker R, Ahmed EU, Ahmed S, Van Nieuwenhuijzen PS, Kemp AH, McGregor IS. Hippocampal protein expression is differentially affected by chronic paroxetine treatment in adolescent and adult rats: a possible mechanism of “paradoxical” antidepressant responses in young persons. Front. Pharmacol. 2013;4:86. doi: Scholar
  6. 6.
    Kölsch H, Ptok U, Majores M, Schmitz S, Rao ML, Maier W, Heun R. Putative association of polymorphism in the mannose 6-phosphate receptor gene with major depression and Alzheimer’s disease. Psychiatr. Genet. 2004;14(2):97-100.CrossRefPubMedGoogle Scholar
  7. 7.
    Kudryavtseva NN. The sensory contact model for the study of aggressive and submissive behaviors in male mice. Aggress. Behav. 1991;17(5):285-291.CrossRefGoogle Scholar
  8. 8.
    Moon HY, Becke A, Berron D, Becker B, Sah N, Benoni G, Janke E, Lubejko ST, Greig NH, Mattison JA, Duzel E, van Praag H. Running-induced systemic cathepsin B secretion is associated with memory function. Cell Metab. 2016;24(2):332-340.CrossRefPubMedGoogle Scholar
  9. 9.
    Pišlar A, Božić B, Zidar N, Kos J. Inhibition of cathepsin X reduces the strength of microglial-mediated neuroinflammation. Neuropharmacology. 2017;114:88-100.CrossRefPubMedGoogle Scholar
  10. 10.
    Pišlar A, Kos J. Cysteine cathepsins in neurological disorders. Mol. Neurobiol. 2014;49(2):1017-1030.CrossRefPubMedGoogle Scholar
  11. 11.
    Ramirez K, Fornaguera-Trías J, Sheridan JF. Stress-induced microglia activation and monocyte trafficking to the brain underlie the development of anxiety and depression. Curr. Top. Behav. Neurosci. 2017;31:155-172.CrossRefPubMedGoogle Scholar
  12. 12.
    Shigematsu N, Fukuda T, Yamamoto T, Nishioku T, Yamaguchi T, Himeno M, Nakayama KI, Tsukuba T, Kadowaki T, Okamoto K, Higuchi S, Yamamoto K. Association of cathepsin Edeficiency with the increased territorial aggressive response of mice. J. Neurochem. 2008;105(4):1394-1404.CrossRefPubMedGoogle Scholar
  13. 13.
    Tholen S, Biniossek ML, Gansz M, Ahrens TD, Schlimpert M, Kizhakkedathu JN, Reinheckel T, Schilling O. Double deficiency of cathepsins B and L results in massive secretome alterations and suggests a degradative cathepsin-MMP axis. Cell. Mol. Life Sci. 2014;71(5):899-916.CrossRefPubMedGoogle Scholar
  14. 14.
    Väänänen AJ, Salmenperä P, Hukkanen M, Miranda KM, Harjula A, Rauhala P, Kankuri E. Persistent susceptibility of cathepsin B to irreversible inhibition by nitroxyl (HNO) in the presence of endogenous nitric oxide. Free Radic. Biol. Med. 2008;45(6):749-755.CrossRefPubMedGoogle Scholar
  15. 15.
    Zhou R, Lu Y, Han Y, Li X, Lou H, Zhu L, Zhen X, Duan S. Mice heterozygous for cathepsin D deficiency exhibit maniarelated behavior and stress-induced depression. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2015;63:110-118.Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • S. Ya. Zhanaeva
    • 1
  • A. A. Rogozhnikova
    • 2
  • E. L. Alperina
    • 1
  • M. M. Gevorgyan
    • 1
  • G. V. Idov
    • 1
    • 2
  1. 1.Research Institute of Physiology and Fundamental MedicineNovosibirskRussia
  2. 2.Novosibirsk National Research State UniversityNovosibirskRussia

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