Skip to main content

Advertisement

Log in

The antidepressant effect of musk in an animal model of depression: a histopathological study

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

A Correction to this article was published on 23 November 2017

This article has been updated

Abstract

Depression is a significant public health concern all over the world, especially in modern communities. This study aims to assess the efficacy of musk in alleviating the behavioral, biochemical and histopathological changes induced by chronic unpredictable mild stress (CUMS) in an animal model of depression and to explore the underlying mechanism of this effect. Male Swiss albino mice were divided into four groups (n = 10): control, CUMS, CUMS+fluoxetine and CUMS+musk. At the end of the experiment, behavioral tests were administered and serum corticosterone and testosterone levels were assessed. Surface markers, proteins and gene expressions of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) in the hippocampus were assessed. The immunoexpression of glial fibrillary acidic protein, Ki67 and caspase-3 was also assessed. Data were analyzed using the Statistical Package for the Social Sciences and a P value of less than 0.05 was considered significant. Musk alleviated the behavioral changes caused by CUMS and reduced elevated corticosterone levels. It reduced CUMS-induced neuronal atrophy in the CA3 and dentate gyrus of the hippocampus and restored astrocytes. Musk reduced the neuro- and glial apoptosis observed in stressed mice in a manner comparable to that of fluoxetine. Musk induced these effects through up-regulating both BDNF and GR gene and protein expressions. Musk has an antidepressant-like effect in an animal model of depression, so it is advisable to assess its efficacy in people continually exposed to stressors.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Change history

  • 23 November 2017

    The original publication of this paper contains mistake. Below you will find the needed corrections:

References

  • Alonso R, Griebel G, Pavone G, Stemmelin J, Le Fur G, Soubrie P (2004) Blockade of CRF1 or V1B receptors reverses stress-induced suppression of neurogenesis in a mouse model of depression. Mol Psychiatry 9:278–286

    Article  CAS  PubMed  Google Scholar 

  • Baker-Herman TL, Fuller DD, Bavis RW, Zabka AG, Golder FJ, Doperalski NJ, Johnson RA, Watters JJ, Mitchell GS (2004) BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia. Nat Neurosci 7(1):48–55

    Article  CAS  PubMed  Google Scholar 

  • Banasr M, Duman RS (2008) Glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors. Biol Psychiatry 64:863–870

    Article  PubMed  PubMed Central  Google Scholar 

  • Banasr M, Dwyer JM, Duman RS (2011) Cell atrophy and loss in depression: reversal by antidepressant treatment. Curr Opin Cell Biol 23:730–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bancroft JD, Gamble M (2008) Theory and practice of histological techniques, 6th edn. Churchill Livingstone, Philadelphia

    Google Scholar 

  • Bataineh HN, Daradka T (2007) Effects of long-term use of fluoxetine on fertility parameters in adult male rats. Neuro Endocrinol Lett 28:321–327

    CAS  PubMed  Google Scholar 

  • Bowley MP, Drevets WC, Ongur D, Price JL (2002) Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry 52:404–412

    Article  PubMed  Google Scholar 

  • Bromet E, Andrade LH, Hwang I, Sampson NA, Alonso J, de Girolamo G, de Graaf R, Demyttenaere K, Hu C, Iwata N, Karam AN, Kaur J, Kostyuchenko S, Lépine JP, Levinson D, Matschinger H, Mora ME, Browne MO, Posada-Villa J, Viana MC, Williams DR, Kessler RC (2011) Cross-national epidemiology of DSM IV major depressive episode. BMC Med 9:90. doi:10.1186/1741-7015-9-90

    Article  PubMed  PubMed Central  Google Scholar 

  • Carobrez AP, Bertoglio LJ (2005) Ethological and temporal analyses of anxiety like behavior: the elevated plus-maze model 20 years on. Neurosci Biobehav Rev 29:1193–1205

    Article  CAS  PubMed  Google Scholar 

  • Castren E, Voikar V, Rantamaki T (2007) Role of neurotrophic factors in depression. Curr Opin Pharmacol 7:18–21

    Article  CAS  PubMed  Google Scholar 

  • Chen BH, Park JH, Cho JH, Kim IH, Shin BN, Ahn JH, Hwang SJ, Yan BC, Tae HJ, Lee JC, Bae EJ, Lee YL, Kim JD, Won MH, Kang IJ (2015) Ethanol extract of Oenanthe javanica increases cell proliferation and neuroblast differentiation in the adolescent rat dentate gyrus. Neural Regen Res 10(2):271–276

    Article  PubMed  PubMed Central  Google Scholar 

  • Chioca LR, Ferro MM, Baretta IP, Oliveira SM, Silva CR, Ferreira J, Losso EM, Andreatini R (2013) Anxiolytic-like effect of lavender essential oil inhalation in mice: participation of serotonergic but notGABAA/benzodiazepine neurotransmission. J Ethnopharmacol 147(2):412–8. doi:10.1016/j.jep.2013.03.028

    Article  CAS  PubMed  Google Scholar 

  • Chourbaji S, Brandwein C, Gass P (2011) Altering BDNF expression by genetics and/or environment: impact for emotional and depression-like behaviour in laboratory mice. Neurosci Biobehav Rev 35(3):599–611. doi:10.1016/j.neubiorev.2010.07.003

    Article  CAS  PubMed  Google Scholar 

  • Doron R, Lotan D, Einat N, Yaffe R, Winer A, Marom I, Meron G, Kately N, Rehavi M (2014) A novel herbal treatment reduces depressive-like behaviors and increases BDNF levels in the brain of stressed mice. Life Sci 94(2):151–7. doi:10.1016/j.lfs.2013.10.025

    Article  CAS  PubMed  Google Scholar 

  • Ducottet C, Belzung C (2004) Behavior in the elevated plus-maze predicts coping after subchronic mild stress in mice. Physiol Behav 81:417–26

    Article  CAS  PubMed  Google Scholar 

  • Duman R (2004) Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromol Med 5:11–26

    Article  CAS  Google Scholar 

  • Egan M, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M et al (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112:257–269

    Article  CAS  PubMed  Google Scholar 

  • Fukayama MY, Easterday OD, Serafino PA, Renskers KJ, North-Root H, Schrankel KR (1999) Subchronic inhalation studies of complex fragrance mixtures in rats and hamsters. Toxicol Lett 111(1-2):175–87

    Article  CAS  PubMed  Google Scholar 

  • Fukui H, Komaki R, Okui M, Toyoshima K, Kuda K (2007) The effects of odor on cortisol and testosterone in healthy adults. Neuro Endocrinol Lett 28(4):433–7

    CAS  PubMed  Google Scholar 

  • Grippo AJ, Sullivan NR, Damjanoska KJ, Crane JW, Carrasco GA, Shi J, Chen Z, Garcia F, Muma NA, Van de Kar LD (2005) Chronic mild stress induces behavioural and physiological changes, and may alter serotonin 1A receptor function, in male and cycling female rats. Psychopharmacology (Berlin) 179:769–780

    Article  CAS  Google Scholar 

  • Hardy MP, Gao HB, Dong Q, Ge R, Wang Q, Chai WR, Feng X, Sottas C (2005) Stress hormone and male reproductive function. Cell Tissue Res 322(1):147–53

    Article  CAS  PubMed  Google Scholar 

  • Ji Q, Li ZG, Tang YS, Mo YP, Yao HJ, Saiyin CK (2014) Effect of electroacupuncture intervention on learning-memory ability and injured hippocampal neurons in depression rats. Zhen Ci Yan Jiu 39(2):136–41

    Google Scholar 

  • Keller J, Flores B, Gomez RG, Solvason HB, Kenna H, Williams GH et al (2006) Cortisol circadian rhythm alterations in psychotic major depression. Biol Psychiatry 60(3):275–81

    Article  CAS  PubMed  Google Scholar 

  • Khan IA, Abourashed EA (2010) Leung’s encyclopedia of common natural ingredients. Wiley, Hoboken, pp 455–465

    Google Scholar 

  • Kilpatrick L, Cahill L (2003) Modulation of memory consolidation for olfactory learning by reversible inactivation of the basolateral amygdala. Behav Neurosci 117:184–188

    Article  PubMed  Google Scholar 

  • Kim YK, Na KS, Myint AM, Leonard BE (2016) The role of proinflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuropsychopharmacol Biol Psychiatry 64:277–84. doi:10.1016/j.pnpbp.2015.06.008

    Article  CAS  PubMed  Google Scholar 

  • Lamers F, Vogelzangs N, Merikangas KR, de Jonge P, Beekman AT, Penninx BW (2013) Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Mol Psychiatry 18(6):692–9

    Article  CAS  PubMed  Google Scholar 

  • Li LF, Yang J, Ma SP, Qu R (2013) Magnolol treatment reversed the glial pathology in an unpredictable chronic mild stress-induced rat model of depression. Eur J Pharmacol 711:42–49

    Article  CAS  PubMed  Google Scholar 

  • Li M, Fu Q, Li Y, Li S, Xue J, Ma S (2014) Emodin opposes chronic unpredictable mild stress induced depressive-like behavior in mice by upregulating the levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor. Fitoterapia 98:1–10

    Article  CAS  PubMed  Google Scholar 

  • Lin DL, Chang HC, Huang SH (2004) Characterization of allegedly musk-containing medicinal products in Taiwan. J Forensic Sci 49(6):1187–93

    Article  CAS  PubMed  Google Scholar 

  • Liu D, Xie K, Yang X, Gu J, Ge L, Wang X, Wang Z (2014) Resveratrol reverses the effects of chronic unpredictable mild stress on behavior, serum corticosterone levels and BDNF expression in rats. Behav Brain Res 264:9–16. doi:10.1016/j.bbr.2014.01.039

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Namba T, Liu J, Suzuki R, Shioda S, Seki T (2010) Glial fibrillary acidic protein-expressing neural progenitors give rise to immature neurons via early intermediate progenitors expressing both glial fibrillary acidic protein and neuronal markers in the adult hippocampus. Neuroscience.166(1):241–51. doi:10.1016/j.neuroscience.2009.12.026

  • Lucassen PJ, Fuchs E, Czéh B (2004) Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex. Biol Psychiatry 8:789–796

    Article  Google Scholar 

  • Makhlouf NA, El-Beshbishy RA, Abousetta A (2014) Ginkgo modulates noise-induced hippocampal damage in male albino rats: a light and electron microscopic study. Egypt J Histol 37(1):159–174. doi:10.1097/01.EHX.0000444078.17248.ab

    Article  Google Scholar 

  • Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20(24):9104–10

    CAS  PubMed  Google Scholar 

  • Manji HK, Duman RS (2001) Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics. Psychopharmacol Bull 35:45–49

    Google Scholar 

  • Mazur A, Booth A (1998) Testosterone and dominance in men. Behav Brain Sci 21:353–397

    Article  CAS  PubMed  Google Scholar 

  • McEwen BS, Magarinos AM (2001) Stress and hippocampal plasticity: implications for the pathophysiology of affective disorders. Hum Psychopharmacol 16:S7–S19

    Article  CAS  PubMed  Google Scholar 

  • Mineur YS, Belzung C, Crusio WE (2006) Effects of unpredictable chronic mild stress on anxiety and depression-like behavior in mice. Behav Brain Res 175:43–50

    Article  PubMed  Google Scholar 

  • Mizuki D, Matsumoto K, Tanaka K, Le Thi X, Fujiwara H, Ishikawa T, Higuchi Y (2014) Antidepressant-like effect of Butea superba in mice exposed to chronic mild stress and its possible mechanism of action. J Ethnopharmacol 156:16–25. doi:10.1016/j.jep.2014.08.014

    Article  PubMed  Google Scholar 

  • Monteggia L (2007) Elucidating the role of brain-derived neurotrophic factor in the brain. Am J Psychiatry 164:1790

    Article  PubMed  Google Scholar 

  • Nemeroff CB (2007) The burden of severe depression: a review of diagnostic challenges and treatment alternatives. J Psychiatr Res 41:189–206

    Article  PubMed  Google Scholar 

  • Oh SR, Lee JP, Chang SY, Shin DH, Ahn KS, Min BS, Lee HK (2002) Androstane alkaloids from musk of Moschus moschiferus. Chem Pharm Bull 50:663–664

    Article  CAS  PubMed  Google Scholar 

  • Pavesi E, Canteras NS, Carobrez AP (2011) Acquisition of Pavlovian fear conditioning using β-adrenoceptor activation of the dorsal premammillary nucleus as an unconditioned stimulus to mimic live predator-threat exposure. Neuropsychopharmacology 36:926–939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paxinos G, Watson C (1998) The rat hippocampus in stereotaxic coordinates. Academic, San Diego

    Google Scholar 

  • Ridder S, Chourbaji S, Hellweg R, Urani A, Zacher C, Schmid W, Zink M, Hörtnagl H, Flor H, Henn FA, Schütz G, Gass P (2005) Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. J Neurosci 25(26):6243–50

    Article  CAS  PubMed  Google Scholar 

  • Rodgers M, Asaria M, Walker S, McMillan D, Lucock M, Harden M, Palmer S, Eastwood A (2012) The clinical effectiveness and cost-effectiveness of low-intensity psychological interventions for the secondary prevention of relapse after depression: a systematic review. Health Technol Assess 16(28):1–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sahay A, Drew MR, Hen R (2007) Dentate gyrus neurogenesis and depression. Prog Brain Res 163:697–722

    Article  CAS  PubMed  Google Scholar 

  • Sakr HF, Abbas AM, Elsamanoudy AZ, Ghoneim FM (2015) Effect of fluoxetine and resveratrol on testicular functions and oxidative stress in a rat model of chronic mildstress-induced depression. J Physiol Pharmacol 66(4):515–27

    CAS  PubMed  Google Scholar 

  • Schmidt NB, Keough ME, Hunter LR, Funk AP (2008) Physical illness and treatment of anxiety disorders: a review. In: Zvolensky MJ, Smits J (eds) Series in anxiety and related disorders: anxiety in health behaviors and physical illness. Springer, New York, pp 341–366

    Chapter  Google Scholar 

  • Seifi Z, Beikmoradi A, Oshvandi K, Poorolajal J, Araghchian M, Safiaryan R (2014) The effect of lavender essential oil on anxiety level in patients undergoing coronary artery bypass graft surgery: a double-blinded randomized clinical trial. Iran J Nurs Midwifery Res 19(6):574–80

    PubMed  PubMed Central  Google Scholar 

  • Song C, Leonard BE (2005) The olfactory bulbectomized rat as a model of depression. Neurosci Biobehav Rev 29:627–647

    Article  PubMed  Google Scholar 

  • Szymánska M, Budziszewska B, Jaworska-Feil L et al (2009) The effect of antidepressant drugs on the HPA axis activity, glucocorticoid receptor level and FKBP51 concentration in prenatally stressed rats. Psychoneuroendocrinology 34(6):822–832

    Article  PubMed  Google Scholar 

  • Vollmayr B, Henn FA (2003) Stress models of depression. Clin Neurosci Res 3:245–251

    Article  Google Scholar 

  • Wang WJ, Zhong M, Guo Y, Zhou LE, Cheng GF, Zhu XY (2003) Effects of musk glucoprotein on chemotaxis of polymorphonuclear leukocytes in vivo and in vitro. Zhongguo Zhong Yao Za Zhi 28(1):59–62

    PubMed  Google Scholar 

  • Warner-Schmidt JL, Duman RS (2006) Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 16(3):239–49

    Article  CAS  PubMed  Google Scholar 

  • Webster MJ, Knable MB, Johnston-Wilson N, Nagata K, Inagaki M, Yolken RH (2001) Immunohistochemical localization of phosphorylated glial fibrillary acidic protein in the prefrontal cortex and hippocampus from patients with schizophrenia, bipolar disorder, and depression. Brain Behav Immun 15:388–400

    Article  CAS  PubMed  Google Scholar 

  • Willner P (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 134(4):319–29

    Article  CAS  PubMed  Google Scholar 

  • Willner P, Scheel-Krüger J, Belzung C (2013) The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev 37(10 Pt 1):2331–71. doi:10.1016/j.neubiorev.2012.12.007

    Article  CAS  PubMed  Google Scholar 

  • Yu HY, Yin ZJ, Yang SJ, Ma SP (2014) Baicalin reverse AMPA receptor expression and neuron apoptosis in chronic unpredictable mild stress rats. Biochem Biophys Res Commun 451(4):467–72. doi:10.1016/j.bbrc.2014.07.041

    Article  CAS  PubMed  Google Scholar 

  • Zunszain PA, Anacker C, Cattaneo A, Carvalho LA, Pariante CM (2011) Glucocorticoids, cytokines and brain abnormalities in depression. Prog Neuropsychopharmacol Biol Psychiatry 35(3):722–9

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This project was funded by the Deanship of Scientific research (DSR), King Abdulaziz University, Jeddah, under grant no. (512/140/1434). The authors, therefore, acknowledge with thanks DSR for their technical and financial support. We would also like to thank Miss Hanaa, the technician at the preclinical research unit, King Fahed medical research center, KAU, for caring for the mice during the experiment.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nasra Naeim Ayuob.

Additional information

A correction to this article is available online at https://doi.org/10.1007/s00441-017-2742-5.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ayuob, N.N., Ali, S.S., Suliaman, M. et al. The antidepressant effect of musk in an animal model of depression: a histopathological study. Cell Tissue Res 366, 271–284 (2016). https://doi.org/10.1007/s00441-016-2468-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-016-2468-9

Keywords

Navigation