Curcumin attenuates development of depressive-like behavior in male rats after spinal cord injury: involvement of NLRP3 inflammasome
Keywords:Spinal Cord Injuries, Depression, Curcumin, Hippocampus, Inflammasome
Objectives: The purpose of this study is investigating curcumin role in mood alterations in male rats after spinal cord injury through focusing on the involvement of NLRP3 inflammasome.
Methods: Fourteen adualt male Wistar rats (220–250 g) were divided to five animal groups (n = 8 per group): Control: healthy animals which received normal saline for 14 days; spinal cord injury: spinal cord injury-induced animals which received normal saline for 14 days; spinal cord injury + curcumin (20, 40, and 80 mg/kg/ i.p): spinal cord injury-induced animals treated with 3 doses of curcumin for 14 days. To assess the mood of animals, the elevated plus maze test, forced swimming test, tail suspension test, and open field test were performed. Graph-pad prism software was used for data analysis. Statistical analysis was done by one-way ANOVA with Tukey’s post hoc test. P < 0.05 was statistically significant.
Results: Treatment with curcumin with two doses of 40 and 80 mg/kg increased open arm time and decreased close arm time as compared to the spinal cord injury group. The administration of curcumin (40 mg/kg and 80 mg/kg) enhanced the altered behaviors. Spinal cord injury caused an increase in the protein levels NLRP3, ASC and Casp1 in the hippocampus of animals as compared to the sham group. Curcumin regulated the protein levels of NLRP3, ASC and Casp1 in the hippocampus of animals.
Conclusion: Depression is prevalent in person with spinal cord injury and our findings indicated that curcumin appears to constitute a suitable agent to reduce neuroinflammation and through it, relieve a depressive-like state.
Alizadeh A, Dyck SM, Karimi-Abdolrezaee S. Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms. Front Neurol. 2019;10:282.
Choobineh H, Kazemi M, Gilani MAS, Heydari T, Shokri S, Bazrafkan M, et al. Testosterone reduces spinal cord injury-induced effects on male reproduction by preventing CADM1 Defect. Cell Journal (Yakhteh). 2018;20(2):138.
Rabinstein AA. Traumatic spinal cord injury. Neurological emergencies. 2020:271-80.
Farkas GJ, Pitot MA, Berg AS, Gater DR. Nutritional status in chronic spinal cord injury: a systematic review and meta-analysis. Spinal Cord. 2019;57(1):3-17.
Gholaminejhad M, Jameie SB, Abdi M, Abolhassani F, Mohammed I, Hassanzadeh G. All-Trans Retinoic Acid–Preconditioned Mesenchymal Stem Cells Improve Motor Function and Alleviate Tissue Damage After Spinal Cord Injury by Inhibition of HMGB1/NF-κB/NLRP3 Pathway Through Autophagy Activation. Journal of Molecular Neuroscience. 2022;72(5):947-62.
Su X-Q, Wang X-Y, Gong F-T, Feng M, Bai J-J, Zhang R-R, et al. Oral treatment with glycyrrhizin inhibits NLRP3 inflammasome activation and promotes microglial M2 polarization after traumatic spinal cord injury. Brain Res Bull. 2020;158:1-8.
Bloom O, Herman PE, Spungen AM. Systemic inflammation in traumatic spinal cord injury. Exp Neurol. 2020;325:113143.
Bazrafkan M, Nikmehr B, Shahverdi A, Hosseini SR, Hassani F, Poorhassan M, et al. Lipid peroxidation and its role in the expression of NLRP1a and NLRP3 genes in testicular tissue of male rats: a model of spinal cord injury. Iranian Biomedical Journal. 2018;22(3):151.
Ghaffari N, Hassanzadeh G, Nowrouzi A, Gholaminejhad M, Mokhtari T, Seifali R. Antioxidative and anti-inflammatory effects of Cichorium intybus L. seed extract in ischemia/reperfusion injury model of rat spinal cord. J Contemp Med Sci. 2018;4:2415.
Ren H, Chen X, Tian M, Zhou J, Ouyang H, Zhang Z. Regulation of inflammatory cytokines for spinal cord injury repair through local delivery of therapeutic agents. Advanced Science. 2018;5(11):1800529.
Jiao J, Zhao G, Wang Y, Ren P, Wu M. MCC950, a selective inhibitor of NLRP3 inflammasome, reduces the inflammatory response and improves neurological outcomes in mice model of spinal cord injury. Frontiers in molecular biosciences. 2020;7:37.
Noori L, Arabzadeh S, Mohamadi Y, Mojaverrostami S, Mokhtari T, Akbari M, et al. Intrathecal administration of the extracellular vesicles derived from human Wharton’s jelly stem cells inhibit inflammation and attenuate the activity of inflammasome complexes after spinal cord injury in rats. Neuroscience research. 2021;170:87-98.
Nikmehr B, Abolhassani F, Hassanzadeh G, Shahverdi A, Bazrafkan M, Hezavehei M, et al., editors. Impaired fertility in a rat model of spinal cord injury and the role of inflammasome complex. HUMAN REPRODUCTION; 2018: OXFORD UNIV PRESS GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND.
Post M, Van Leeuwen C. Psychosocial issues in spinal cord injury: a review. Spinal cord. 2012;50(5):382-9.
Elliott TR, Frank RG. Depression following spinal cord injury. Arch Phys Med Rehabil. 1996;77(8):816-23.
Williams R, Murray A. Prevalence of depression after spinal cord injury: a meta-analysis. Arch Phys Med Rehabil. 2015;96(1):133-40.
Kennedy P, Rogers BA. Anxiety and depression after spinal cord injury: a longitudinal analysis. Archives of physical medicine and rehabilitation. 2000;81(7):932-7.
Budh CN, Österåker A-L. Life satisfaction in individuals with a spinal cord injury and pain. Clin Rehabil. 2007;21(1):89-96.
Putzke JD, Richards JS, Hicken BL, DeVivo MJ. Predictors of life satisfaction: a spinal cord injury cohort study. Arch Phys Med Rehabil. 2002;83(4):555-61.
Luedtke K, Bouchard SM, Woller SA, Funk MK, Aceves M, Hook MA. Assessment of depression in a rodent model of spinal cord injury. J Neurotrauma. 2014;31(12):1107-21.
Fullerton DT, Harvey RF, Klein MH, Howell T. Psychiatric disorders in patients with spinal cord injuries. Arch Gen Psychiatry. 1981;38(12):1369-71.
Brakel K, Hook MA. SCI and depression: does inflammation commandeer the brain? Exp Neurol. 2019;320:112977.
Maldonado-Bouchard S, Peters K, Woller SA, Madahian B, Faghihi U, Patel S, et al. Inflammation is increased with anxiety-and depression-like signs in a rat model of spinal cord injury. Brain Behav Immun. 2016;51:176-95.
Berk M, Williams LJ, Jacka FN, O’Neil A, Pasco JA, Moylan S, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013;11(1):1-16.
Nerurkar L, Siebert S, McInnes IB, Cavanagh J. Rheumatoid arthritis and depression: an inflammatory perspective. The Lancet Psychiatry. 2019;6(2):164-73.
Capuron L, Fornwalt FB, Knight BT, Harvey PD, Ninan PT, Miller AH. Does cytokine-induced depression differ from idiopathic major depression in medically healthy individuals? J Affect Disord. 2009;119(1-3):181-5.
Sonsin-Diaz N, Gottesman RF, Fracica E, Walston J, Windham BG, Knopman DS, et al. Chronic systemic inflammation is associated with symptoms of late-life depression: the ARIC study. The American Journal of Geriatric Psychiatry. 2020;28(1):87-98.
Straub RH. Interaction of the endocrine system with inflammation: a function of energy and volume regulation. Arthritis Res Ther. 2014;16(1):1-15.
Manley K, Han W, Zelin G, Lawrence DA. Crosstalk between the immune, endocrine, and nervous systems in immunotoxicology. Current Opinion in Toxicology. 2018;10:37-45.
Leonard BE, Myint A. The psychoneuroimmunology of depression. Human Psychopharmacology: clinical and experimental. 2009;24(3):165-75.
Ferguson AR, Hook MA, Garcia G, Bresnahan JC, Beattie MS, Grau JW. A simple post hoc transformation that improves the metric properties of the BBB scale for rats with moderate to severe spinal cord injury. J Neurotrauma. 2004;21(11):1601-13.
Bethea JR. Spinal cord injury-induced inflammation: a dual-edged sword. Prog Brain Res. 2000;128:33-42.
Brakel K, Aceves M, Garza A, Yoo C, Escobedo Jr G, Panchani N, et al. Inflammation increases the development of depression behaviors in male rats after spinal cord injury. Brain, Behavior, & Immunity-Health. 2021;14:100258.
Dantzer R, O'connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nature reviews neuroscience. 2008;9(1):46-56.
Stepanichev M, Dygalo NN, Grigoryan G, Shishkina GT, Gulyaeva N. Rodent models of depression: neurotrophic and neuroinflammatory biomarkers. BioMed research international. 2014;2014.
Sakamoto S, Zhu X, Hasegawa Y, Karma S, Obayashi M, Alway E, et al. Inflamed brain: Targeting immune changes and inflammation for treatment of depression. Psychiatry Clin Neurosci. 2021;75(10):304-11.
Strawbridge R, Arnone D, Danese A, Papadopoulos A, Vives AH, Cleare A. Inflammation and clinical response to treatment in depression: a meta-analysis. Eur Neuropsychopharmacol. 2015;25(10):1532-43.
Lestari ML, Indrayanto G. Curcumin. Profiles of drug substances, excipients and related methodology. 2014;39:113-204.
Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75(4):787-809.
Hussain Z, Thu HE, Amjad MW, Hussain F, Ahmed TA, Khan S. Exploring recent developments to improve antioxidant, anti-inflammatory and antimicrobial efficacy of curcumin: A review of new trends and future perspectives. Materials science and engineering: C. 2017;77:1316-26.
Zu J, Wang Y, Xu G, Zhuang J, Gong H, Yan J. Curcumin improves the recovery of motor function and reduces spinal cord edema in a rat acute spinal cord injury model by inhibiting the JAK/STAT signaling pathway. Acta Histochem. 2014;116(8):1331-6.
Kavakli HS, Koca C, Alici O. Antioxidant effects of curcumin in spinal cord injury in rats. Ulus Travma Acil Cerrahi Derg. 2011;17(1):14-8.
Ebrahimi B, Estaji M, Rajabzadeh A. The effect of different doses of glibenclamide on blood glucose and islet volume in diabetic rats. Navid No. 2019;21(68):10-8.
Ebrahimi B, Azizi H, Sarkarizi HK, Bahrami-Taghanaki H, Rajabzadeh A. Comparing The Effect Of Electroacupuncture And Glibenclamide On Blood Glucose Level And Histological Markers Of Pancreas In Streptozotocin-Induced Diabetic Rats. Alternative Therapies in Health & Medicine. 2020;26.
Xie Z, Huang S, Xie S, Zhou W, Li C, Xing Z, et al. Potential correlation between depression-like behavior and the mitogen-activated protein kinase pathway in the rat hippocampus following spinal cord injury. World Neurosurgery. 2021;154:e29-e38.
Ereshefsky L, Sloan D. Drug-drug interactions with the use of psychotropic medications. CNS Spectr. 2009;14(8):1-8.
Ramaholimihaso T, Bouazzaoui F, Kaladjian A. Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review. Frontiers in Psychiatry. 2020:1302.
Zhang W-y, Guo Y-j, Han W-x, Yang M-q, Wen L-p, Wang K-y, et al. Curcumin relieves depressive-like behaviors via inhibition of the NLRP3 inflammasome and kynurenine pathway in rats suffering from chronic unpredictable mild stress. International Immunopharmacology. 2019;67:138-44.
Fan C, Song Q, Wang P, Li Y, Yang M, Liu B, et al. Curcumin protects against chronic stress-induced dysregulation of neuroplasticity and depression-like behaviors via suppressing IL-1β pathway in rats. Neuroscience. 2018;392:92-106.
Xu Y, Ku B-S, Yao H-Y, Lin Y-H, Ma X, Zhang Y-H, et al. The effects of curcumin on depressive-like behaviors in mice. European journal of pharmacology. 2005;518(1):40-6.
Lin M-S, Lee Y-H, Chiu W-T, Hung K-S. Curcumin provides neuroprotection after spinal cord injury. Journal of Surgical Research. 2011;166(2):280-9.
Wang Y-F, Zu J-N, Li J, Chen C, Xi C-Y, Yan J-L. Curcumin promotes the spinal cord repair via inhibition of glial scar formation and inflammation. Neuroscience letters. 2014;560:51-6.
Yuan J, Zou M, Xiang X, Zhu H, Chu W, Liu W, et al. Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar. Journal of Surgical Research. 2015;195(1):235-45.
Limcharoen T, Muangnoi C, Wasana PWD, Vajragupta O, Rojsitthisak P, Towiwat P. Improved antiallodynic, antihyperalgesic and anti-inflammatory response achieved through potential prodrug of curcumin, curcumin diethyl diglutarate in a mouse model of neuropathic pain. European Journal of Pharmacology. 2021;899:174008.
Yu J-J, Pei L-B, Zhang Y, Wen Z-Y, Yang J-L. Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Journal of clinical psychopharmacology. 2015;35(4):406-10.
Jin W, Botchway BO, Liu X. Curcumin can activate the Nrf2/HO-1 signaling pathway and scavenge free radicals in spinal cord injury treatment. Neurorehabilitation and Neural Repair. 2021;35(7):576-84.
Yardım A, Kandemir FM, Çomaklı S, Özdemir S, Caglayan C, Kucukler S, et al. Protective effects of curcumin against paclitaxel-induced spinal cord and sciatic nerve injuries in rats. Neurochemical Research. 2021;46(2):379-95.
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