Skip to main content

Advertisement

Log in

The Association of Major Depressive Disorder with Activation of NLRP3 Inflammasome, Lipid Peroxidation, and Total Antioxidant Capacity

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Increasing number of studies indicates that chronic inflammation and oxidative stress play an essential role in pathophysiology and some symptoms of major depressive disorder (MDD). In the present study, the inflammasome activity and oxidative stress status in untreated and antidepressant-treated MDD patients were compared to the healthy group. Blood samples were taken from 20 MDD patients receiving treatment, 20 first-episode MDD patients not receiving treatment, and 20 healthy controls. The expression level of NLRP3 and caspase-1 was measured by real-time PCR and the serum TAC and MDA were examined in the patients and the control groups. The results showed that the mRNA level of NLRP3 and caspase-1 genes was significantly elevated in MDD groups compared with that in the healthy volunteers (P < 0.005). The expression level of NLRP3 and caspase-1 has slightly decreased in the treated group compared with that in the untreated one, but it was not a meaningful decrease. Moreover, the serum MDA was significantly higher and TAC statistically was lower in untreated MDD patients compared with those in the healthy control group (P = 0.001, P = 0.001). It can be concluded that NLRP3 inflammasome is upregulated in MDD patients. Statistically significant reduction in the level of TAC along with increased lipid peroxidation was detectable in MDD patient’s plasma. In contrast, there was no significant difference between the treated and non-treated groups in terms of oxidative stress (P = 0.6, P = 0.1). Our results suggested that inflammasome signaling pathway is a therapeutic potential for MDD.

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

Similar content being viewed by others

References

  • Alcocer-Gómez, E., de Miguel, M., Casas-Barquero, N., Núñez-Vasco, J., Sánchez-Alcazar, J. A., Fernández-Rodríguez, A., & Cordero, M. D. (2014). NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain, behavior, and immunity, 36, 111–117.

  • Alcocer-Gómez E, Casas-Barquero N, Williams MR, Romero-Guillena SL, Cañadas-Lozano D, Bullón P et al (2017) Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in major depressive disorder. Pharmacol Res 121:114–121

    Article  Google Scholar 

  • Bilici M, Efe H, Köroğlu MA, Uydu HA, Bekaroğlu M, Değer O (2001) Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord 64(1):43–51

    Article  CAS  Google Scholar 

  • Chaurasia SS, Lim RR, Parikh BH, Wey YS, Tun BB, Wong TY et al (2018) The NLRP3 inflammasome may contribute to pathologic neovascularization in the advanced stages of diabetic retinopathy. Sci Rep 8(1):2847

    Article  Google Scholar 

  • Chen H, Zhang X, Liao N, Mi L, Peng Y, Liu B et al (2018) Enhanced expression of NLRP3 inflammasome-related inflammation in diabetic retinopathy. Invest Ophthalmol Vis Sci 59(2):978–985

    Article  CAS  Google Scholar 

  • Cumurcu BE, Ozyurt H, Etikan I, Demir S, Karlidag R (2009) Total antioxidant capacity and total oxidant status in patients with major depression: impact of antidepressant treatment. Psychiatry Clin Neurosci 63(5):639–645

    Article  CAS  Google Scholar 

  • Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010). A meta-analysis of cytokines in major depression. Biological psychiatry, 67(5), 446–457.

  • Fann DYW, Lim YA, Cheng YL et al (2018) Mol Neurobiol 55:1082. https://doi.org/10.1007/s12035-017-0394-9

    Article  CAS  PubMed  Google Scholar 

  • Hannestad J, DellaGioia N, Bloch M (2011) The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 36(12):2452

    Article  CAS  Google Scholar 

  • Iwata M, Ota KT, Duman RS (2013) The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav Immun 31:105–114

    Article  CAS  Google Scholar 

  • Jo EK, Kim JK, Shin DM, Sasakawa C (2016) Molecular mechanisms regulating NLRP3 inflammasome activation. Cellular & molecular immunology 13(2):148–159. https://doi.org/10.1038/cmi.2015.95

    Article  CAS  Google Scholar 

  • Kessler RC, Birnbaum H, Bromet E, Hwang I, Sampson N, Shahly V (2010) Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R). Psychol Med 40(2):225–237

    Article  CAS  Google Scholar 

  • Khanzode SD, Dakhale GN, Khanzode SS, Saoji A, Palasodkar R (2003) Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep 8(6):365–370

    Article  CAS  Google Scholar 

  • Kunz M, Gama CS, Andreazza AC, Salvador M, Ceresér KM, Gomes FA et al (2008) Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 32(7):1677–1681

    Article  CAS  Google Scholar 

  • Leo R, Di GL, Tesauro M, Razzini C, Forleo GB, Chiricolo G et al (2006) Association between enhanced soluble CD40 ligand and proinflammatory and prothrombotic states in major depressive disorder: pilot observations on the effects of selective serotonin reuptake inhibitor therapy. The Journal of clinical psychiatry 67(11):1760–1766

    Article  CAS  Google Scholar 

  • Marim FM, Franco M, Gomes M, Miraglia MC, Giambartolomei GH, Oliveira SC (2017) The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection. Semin Immunopathol 39(2):215–223

    Article  CAS  Google Scholar 

  • Miller AH, Raison CL (2016) The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol 16(1):22–34

    Article  CAS  Google Scholar 

  • Patel A (2013) The role of inflammation in depression. Psychiatr Danub 25(Suppl 2):S216–S223

    PubMed  Google Scholar 

  • Resler G, Lavie R, Campos J, Mata S, Urbina M, García A et al (2008) Effect of folic acid combined with fluoxetine in patients with major depression on plasma homocysteine and vitamin B12, and serotonin levels in lymphocytes. Neuroimmunomodulation 15(3):145–152

    Article  CAS  Google Scholar 

  • Sajadi SMA, Mirzaei V, Hassanshahi G, Khorramdelazad H, Daredor HY, Hosseini SMH et al (2013) Decreased expressions of Toll-like receptor 9 and its signaling molecules in chronic hepatitis B virus–infected patients. Arch Pathol Lab Med 137(11):1674–1679

    Article  CAS  Google Scholar 

  • Sarandol A, Sarandol E, Eker SS, Erdinc S, Vatansever E, Kirli S (2007) Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative–antioxidative systems. Hum Psychopharmacol Clin Exp 22(2):67–73

    Article  CAS  Google Scholar 

  • Slavich GM, Irwin MR (2014) From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychological Bulletin 140(3):774–815

    Article  Google Scholar 

  • Varghese GP, Folkersen L, Strawbridge RJ, Halvorsen B, Yndestad A, Ranheim T et al (2016) NLRP3 inflammasome expression and activation in human atherosclerosis. J Am Heart Assoc 5(5):e003031

    Google Scholar 

  • Wang Y, Xu Y, Sheng H, Ni X, Lu J (2016) Exercise amelioration of depression-like behavior in OVX mice is associated with suppression of NLRP3 inflammasome activation in hippocampus. Behav Brain Res 307:18–24. https://doi.org/10.1016/j.bbr.2016.03.044

    Article  CAS  PubMed  Google Scholar 

  • Yao JK, Leonard S, Reddy R (2006) Altered glutathione redox state in schizophrenia. Disease markers 22(1, 2):83–93

    Article  CAS  Google Scholar 

  • Zhu W, Cao F-S, Feng J, Chen H-W, Wan J-R, Lu Q, Wang J (2017) NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide. Neuroscience 343:77–84

    Article  CAS  Google Scholar 

Download references

Funding

The author(s) disclosed the receipt of the following financial support for the research: This work was supported by Birjand University of Medical Sciences (grant number 4464).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gholamreza Anani Sarab.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Taene, A., Khalili-Tanha, G., Esmaeili, A. et al. The Association of Major Depressive Disorder with Activation of NLRP3 Inflammasome, Lipid Peroxidation, and Total Antioxidant Capacity. J Mol Neurosci 70, 65–70 (2020). https://doi.org/10.1007/s12031-019-01401-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-019-01401-0

Keywords

Navigation