Curcumin and exercise prevent depression via alleviating hippocampus injury and improve depressive-like behaviors in chronically stressed depression rats

Elaheh Ahmadi, Ali Pourmotabbed, Nilofar Aghaz, Seyed Ershad Nedaei, Mojgan Veisi, Zahra Salimi, Fatemeh Zarei, Cyrus Jalili, Farshad Moradpour, Motahareh Zeinivand

Abstract


Background and purpose: Depression is a growing public health concern worldwide, characterized by cognitive impairment and structural abnormalities of the hippocampus. Current antidepressant treatment sometimes causes the late onset of results and the much faster occurrence of side effects. For this reason, the interest in new treatment strategies including exercise and natural products such as curcumin has increased to treat depression. The present study investigated the role of curcumin and exercise in improving depressive-like behavior and hippocampal damage induced by mild unpredictable chronic stress in male rats.

Experimental approach: This study analyzed the effects of curcumin (100 mg/kg/day, P.O for 14 days) and exercise (treadmill running, 45 min/day for 14 days) on immobility behavior (forced swimming test), locomotor activity (open field test), anhedonia (sucrose preference test) and cell survival (Nissl staining) of the hippocampal CA3 region in chronically stressed depression rats.

Findings/Results: In the current study, curcumin treatment combined with exercise effectively improved immobility behavior, locomotor activity, and increased hippocampal cell survival resulted in preventing the development of hippocampus dysfunction and depressive-like behaviors.

Conclusion and implications: This study demonstrated a new prospect for treating depression. The current findings give researchers the confidence to continue the investigations on the effects of curcumin accompanied with exercise as a novel therapy for the treatment of depression.

 

 


Keywords


Chronic stress; Curcumin; Depressive behaviors; Exercise; Hippocampus injury.

Full Text:

PDF

References


Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJL, et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013;10(11):e1001547,1-12.DOI: 10.1371/journal.pmed.1001547.

Cao X, Zhou J, Liu J, Chen H, Zheng W. Aromatherapy in anxiety, depression, and insomnia: a bibliometric study and visualization analysis. Heliyon. 2023;9(7):e18380,1-13.DOI: 10.1016/j.heliyon.2023.e18380.

Sivertsen H, Bjørkløf GH, Engedal K, Selbæk G, Helvik AS. Depression and quality of life in older persons: a review. Dement Geriatr Cogn Disord. 2015;40(5-6):311-319.DOI: 10.1159/000437299.

Alshaya DS. Genetic and epigenetic factors associated with depression: an updated overview. Saudi J Biol Sci. 2022;29(8):103311,1-11.DOI: 10.1016/j.sjbs.2022.103311.

Cheng Q, Huang J, Xu L, Li Y, Li H, Shen Y, et al. Analysis of time-course, dose-effect, and influencing factors of antidepressants in the treatment of acute adult patients with major depression. Int J Neurophamacol. 2020;23(2):76-87.DOI: 10.1093/ijnp/pyz062.

Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report. Am J Psychiatry. 2006;163(11):1905-1917.DOI: 10.1176/ajp.2006.163.11.1905.

Zhang Y, Li L, Zhang J. Curcumin in antidepressant treatments: an overview of potential mechanisms, pre‐clinical/clinical trials and ongoing challenges. Basic Clin Pharmacol Toxicol. 2020;127(4):243-253.DOI: 10.1111/bcpt.13455.

Zhong X, Harris G, Smirnova L, Zufferey V, de Cássia da Silveira E Sá R, Russo FB, et al. Antidepressant paroxetine exerts developmental neurotoxicity in an iPSC-derived 3D human brain model. Front Cell Neurosci. 2020;14:25,1-11.DOI: 10.3389/fncel.2020.00025.

Fusar-Poli L, Vozza L, Gabbiadini A, Vanella A, Concas I, Tinacci S, et al. Curcumin for depression: a meta-analysis. Crit Rev Food Sci Nutr. 2020;60(15):2643-2653.DOI: 10.1080/10408398.2019.1653260.

Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, et al. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis. 2007;28(8):1765-1773.DOI: 10.1093/carcin/bgm123.

Wang R, Xu Y, Wu HL, Li YB, Li YH, Guo JB, et al. The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors. Eur J Pharmacol. 2008;578(1):43-50.DOI: 10.1016/j.ejphar.2007.08.045.

Chin KY. The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis. Drug Des Devel Ther. 2016;10: 3029-3042.DOI: 10.2147/DDDT.S117432.

Adahoun MA, Al-Akhras MAH, Jaafar MS, Bououdina M. Enhanced anti-cancer and antimicrobial activities of curcumin nanoparticles. Artif Cells Nanomed Biotechnol. 2017;45(1):98-107.DOI: 10.3109/21691401.2015.1129628.

Yan FS, Sun JL, Xie WH, Shen L, Ji HF. Neuroprotective effects and mechanisms of curcumin–Cu (II) and–Zn (II) complexes systems and their pharmacological implications. Nutrients. 2017;10(1):28,1-11.DOI: 10.3390/nu10010028.

Farris SG, Abrantes AM, Uebelacker LA, Weinstock LM, Battle CL. Exercise as a nonpharmacological treatment for depression. Psychiatr Ann. 2019;49(1):6-10.DOI: 10.3928/00485713-20181204-01.

Harvey SB, Øverland S, Hatch SL, Wessely S, Mykletun A, Hotopf M. Exercise and the prevention of depression: results of the HUNT cohort study. Am J Psychiatry. 2018;175(1):28-36.DOI: 10.1176/appi.ajp.2017.16111223.

Swain D, Nanda P, Das H. Impact of yoga intervention on menopausal symptoms‐specific quality of life and changes in hormonal level among menopausal women. J Obstet Gynaecol Res. 2021;47(10):3669-3676.DOI: 10.1111/jog.14939.

Ho CWH, Chan SC, Wong JS, Cheung WT, Chung DWS, Lau TFO. Effect of aerobic exercise training on Chinese population with mild to moderate depression in Hong Kong. Rehabil Res Pract. 2014;2014:627376,1-8.DOI: 10.1155/2014/627376.

Liu W, Xue X, Xia J, Liu J, Qi Z. Swimming exercise reverses CUMS-induced changes in depression-like behaviors and hippocampal plasticity-related proteins. J Affect Disord. 2018;227:126-135.DOI: 10.1016/j.jad.2017.10.019.

Lopresti AL, Drummond PD. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: a randomised, double-blind, placebo-controlled study. J Affect Disord. 2017;207:188-196.DOI: 10.1016/j.jad.2016.09.047.

Giollabhui NM. Inflammation and depression: research designs to better understand the mechanistic relationships between depression, inflammation, cognitive dysfunction, and their shared risk factors. Brain Behav Immun Health. 2021;15:100278,1-7.DOI: 10.1016/j.bbih.2021.100278.

Eisch AJ, Petrik D. Depression and hippocampal neurogenesis: a road to remission? Science. 2012; 338(6103):72-75.DOI: 10.1126/science.1222941.

Zavvari F, Nahavandi A. Fluoxetine increases hippocampal neural survival by improving axonal transport in stress-induced model of depression male rats. Physiol Behav. 2020;227:113140,1-8.DOI: 10.1016/j.physbeh.2020.113140.

Attari F, Sharifi N, Movassaghi S, Aligholi H, AlLzamir T, Hassanzadeh G. Neuroprotective effects of curcumin against transient global ischemia are dose and area dependent. Arch Neurosci. 2016;3(2):1-8.DOI:10.5812/archneurosci.32600.

Grønli J, Murison R, Fiske E, Bjorvatn B, Sørensen E, Portas CM, et al. Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions. Physiol Behav. 2005;84(4):571-577.DOI: 10.1016/j.physbeh.2005.02.007.

Fahey B, Barlow S, Day JS, O'Mara SM. Interferon-α-induced deficits in novel object recognition are rescued by chronic exercise. Physiol Behav. 2008;95(1-2):125-129.DOI: 10.1016/j.physbeh.2008.05.008.

Slattery DA, Cryan JF. Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc. 2012;7(6):1009-1014.DOI: 10.1038/nprot.2012.044.

Alamri HS, Mufti R, Sabir DK, Abuderman AA, Dawood AF, ShamsEldeen AM, et al. Forced swimming-induced depressive-like behavior and anxiety are reduced by chlorpheniramine via suppression of oxidative and inflammatory mediators and activating the Nrf2-BDNF signaling pathway. Curr Issue Mol Biol. 2023;45(8):6449-6465.DOI: 10.3390/cimb45080407.

Fang W, Xiao N, Zeng G, Bi D, Dai X, Mi X, et al. APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline. Transl Psychiatry. 2021;11(1):603,1-2.DOI: 10.1038/s41398-021-01721-z.

Nakagawa H, Matsunaga D, Ishiwata T. Effect of heat acclimation on anxiety-like behavior of rats in an open field. J Therm Biol. 2020;87:102458,1-5.DOI: 10.1016/j.jtherbio.2019.102458.

Himanshu, Dharmila, Sarkar D, Nutan. A review of behavioral tests to evaluate different types of anxiety and anti-anxiety effects. Clin Psychopharmacol Neurosci. 2020;18(3):341-351.DOI: 10.9758/cpn.2020.18.3.341.

Berrio JP, Kalliokoski O. Rethinking data treatment: the sucrose preference threshold for anhedonia in stress-induced rat models of depression. J Neurosci Methods. 2023;395:109910,1-11.DOI: 10.1016/j.jneumeth.2023.109910.

Farooq RK, Isingrini E, Tanti A, Le Guisquet AM, Arlicot N, Minier F, et al. Is unpredictable chronic mild stress (UCMS) a reliable model to study depression-induced neuroinflammation? Behav Brain Res. 2012;231(1):130-137.DOI: 10.1016/j.bbr.2012.03.020.

Rahchamani M, Movassaghi S, Kermaniha Z, Sharifi N. Effect of propofol on hippocampal CA2 and CA3 cells in rat model of ischemic/reperfusion. Medical Sciences Journal. 2022;32(4):389-397.DOI: 10.52547/iau.32.4.389.

Fang Y, Guo H, Wang Q, Liu C, Ge S, Yan B. The role and mechanism of NLRP3 inflammasome-mediated astrocyte activation in dehydrocorydaline against CUMS-induced depression. Front Pharmacol. 2022;13:1008249,1-15.DOI: 10.3389/fphar.2022.1008249.

Price RB, Duman R. Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model. Mol Psychiatry. 2020;25(3):530-543.DOI: 10.1038/s41380-019-0615-x.

Jin X, Zhu L, Lu S, Li C, Bai M, Xu E, et al. Baicalin ameliorates CUMS-induced depression-like behaviors through activating AMPK/PGC-1α pathway and enhancing NIX-mediated mitophagy in mice. Eur J Pharmacol. 2023;938:175435.DOI: 10.1016/j.ejphar.2022.175435.

Micheli L, Ceccarelli M, D’Andrea G, Tirone F. Depression and adult neurogenesis: positive effects of the antidepressant fluoxetine and of physical exercise. Brain Res Bull. 2018;143:181-193.

DOI: 10.1016/j.brainresbull.2018.09.002.

Cobb JA, Simpson J, Mahajan GJ, Overholser JC, Jurjus GJ, Dieter L, et al. Hippocampal volume and total cell numbers in major depressive disorder. J Psychiatr Res. 2013;47(3):299-306.DOI: 10.1016/j.jpsychires.2012.10.020.

Qiao H, An SC, Ren W, Ma XM. Progressive alterations of hippocampal CA3-CA1 synapses in an animal model of depression. Behav Brain Res. 2014;275:191-200.DOI: 10.1016/j.bbr.2014.08.040.

Ortiz JB, Conrad CD. The impact from the aftermath of chronic stress on hippocampal structure and function: is there a recovery? Front Neuroendocrinol. 2018;49:114-123.DOI: 10.1016/j.yfrne.2018.02.005.

Fan C, Song Q, Wang P, Li Y, Yang M, Yu SY. Neuroprotective effects of curcumin on IL-1β-induced neuronal apoptosis and depression-like behaviors caused by chronic stress in rats. Front Cell Neurosci. 2018;12:516,1-17.DOI: 10.3389/fncel.2018.00516.

Li C, Wang Q, Luo L, Xu X, Liu T, Yang D, et al. Effects of exercise on inflammation and apoptosis of hippocampal neurons in post-stroke depression. Chinese Journal of Physical Medicine and Rehabilitation. 2020;12:577-582.

da Silva Marques JG, Antunes FTT, da Silva Brum LF, Pedron C, de Oliveira IB, de Barros Falcão Ferraz A, et al. Adaptogenic effects of curcumin on depression induced by moderate and unpredictable chronic stress in mice. Behav Brain Res. 2021;399:113002,1-28.DOI: 10.1016/j.bbr.2020.113002.

Fitzgerald PJ, Yen JY, Watson BO. Stress-sensitive antidepressant-like effects of ketamine in the mouse forced swim test. PloS One. 2019;14(4):e0215554,1-17.DOI: 10.1371/journal.pone.0215554.

Kara NZ, Stukalin Y, Einat H. Revisiting the validity of the mouse forced swim test: systematic review and meta-analysis of the effects of prototypic antidepressants. Neurosci Biobehav Rev. 2018;84:1-11.DOI: 10.1016/j.neubiorev.2017.11.003.

Markov DD. Sucrose preference test as a measure of anhedonic behavior in a chronic unpredictable mild stress model of depression: outstanding issues. Brain Sci. 2022;12(10):1287,1-20.DOI: 10.3390/brainsci12101287.

Gueye AB, Vendruscolo LF, de Avila C, Le Moine C, Darnaudéry M, Cador M. Unlimited sucrose consumption during adolescence generates a depressive-like phenotype in adulthood. Neuropsychopharmacology. 2018;43(13):2627-2635.DOI: 10.1038/s41386-018-0025-9.

Horsey EA, Maletta T, Turner H, Cole C, Lehmann H, Fournier NM. Chronic jet lag simulation decreases hippocampal neurogenesis and enhances depressive behaviors and cognitive deficits in adult male rats. Front Behav Neurosci. 2020;13:272,1-14.DOI: 10.3389/fnbeh.2019.00272.

Rubab S, Naeem K, Rana I, Khan N, Afridi M, Ullah I, et al. Enhanced neuroprotective and antidepressant activity of curcumin-loaded nanostructured lipid carriers in lipopolysaccharide-induced depression and anxiety rat model. Int J Pharm. 2021;603:120670,1-13.DOI: 10.1016/j.ijpharm.2021.120670.


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.