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Boophone disticha attenuates five day repeated forced swim-induced stress and adult hippocampal neurogenesis impairment in male Balb/c mice

  • Nkosiphendule Khuthazelani Xhakaza (School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand) ;
  • Pilani Nkomozepi (Department of Human Anatomy and Physiology, Faculty of Health Sciences, University of Johannesburg) ;
  • Ejekemi Felix Mbajiorgu (School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand)
  • Received : 2022.06.20
  • Accepted : 2022.09.06
  • Published : 2023.03.31

Abstract

Depression is one of the most common neuropsychiatric disorders and is associated with dysfunction of the neuroendocrine system and alterations in specific brain proteins. Boophone disticha (BD) is an indigenous psychoactive bulb that belongs to the Amaryllidacae family, which is widely used in Southern Africa to treat depression, with scientific evidence of potent antidepressant-like effects. The present study examined the antidepressant effects of BD and its mechanisms of action by measuring some behavioural parameters in the elevated plus maze, brain content of corticosterone, brain derived neurotropic factor (BDNF), and neuroblast differentiation in the hippocampus of Balb/c mice exposed to the five day repeated forced swim stress (5d-RFSS). Male Balb/c mice were subjected to the 5d-RFSS protocol to induce depressive-like behaviour (decreased swimming, increased floating, decreased open arm entry, decreased time spent in the open arms and decreased head dips in the elevated plus maze test) and treated with distilled water, fluoxetine and BD. BD treatment (10 mg/kg/p.o for 3 weeks) significantly attenuated the 5d-RFSS-induced behavioural abnormalities and the elevated serum corticosterone levels observed in stressed mice. Additionally, 5d-RFSS exposure significantly decreased the number of neuroblasts in the hippocampus and BDNF levels in the brain of Balb/c mice, while fluoxetine and BD treatment attenuated these changes. The antidepressant effects of BD were comparable to those of fluoxetine, but unlike fluoxetine, BD did not show any anxiogenic effects, suggesting better pharmacological functions. In conclusion, our study shows that BD exerted antidepressant-like effects in 5d-RFSS mice, mediated in part by normalizing brain corticosterone and BDNF levels.

Keywords

Acknowledgement

The authors would like to greatly appreciate the following South African institutions for funding the study: Thuthuka grant (TTK190215418278) of the National Research Foundation (NRF) and Sefako Makgatho Health Sciences University (D407).

References

  1. Vigo D, Thornicroft G, Atun R. Estimating the true global burden of mental illness. Lancet Psychiatry 2016;3:171-8.
  2. Zayka TO, Evdokimov DV, Sidorova YV, Abramets II, Nalotov SV. Antidepressant-like effects of substances with cerebroprotective activity. Biol Markers Guided Ther 2015;2:79-88.
  3. Anacker C. Fresh approaches to antidepressant drug discovery. Expert Opin Drug Discov 2014;9:407-21.
  4. Hornung OP, Heim CM. Gene-environment interactions and intermediate phenotypes: early trauma and depression. Front Endocrinol (Lausanne) 2014;5:14.
  5. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003;289:3095-105.
  6. Kharamin S, Razmeh S, Nabovvati M, Moradian K, Rahimi S, Orooji M, Taghavian L, Mand Maher MK. Evaluation of antidepressant-like effect Lavandulifolia stachys in the forced swimming test in comparison with imipramine and fluoxetine. Int J Plant Biol 2019;10:7458.
  7. Panwar R, Sivakumar M, Menon V, Vairappan B. Changes in the levels of comet parameters before and after fluoxetine therapy in major depression patients. Anat Cell Biol 2020;53:194-200.
  8. Bagdy G, Graf M, Anheuer ZE, Modos EA, Kantor S. Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635. Int J Neuropsychopharmacol 2001;4:399-408.
  9. Nutt DJ. Overview of diagnosis and drug treatments of anxiety disorders. CNS Spectr 2005;10:49-56.
  10. Birkett MA, Shinday NM, Kessler EJ, Meyer JS, Ritchie S, Rowlett JK. Acute anxiogenic-like effects of selective serotonin reuptake inhibitors are attenuated by the benzodiazepine diazepam in BALB/c mice. Pharmacol Biochem Behav 2011;98:544-51.
  11. Ramaekers JG. Antidepressants and driver impairment: empirical evidence from a standard on-the-road test. J Clin Psychiatry 2003;64:20-9.
  12. Sandager M, Nielsen ND, Stafford GI, van Staden J, Jager AK. Alkaloids from Boophane disticha with affinity to the serotonin transporter in rat brain. J Ethnopharmacol 2005;98:367-70.
  13. Gadaga LL, Tagwireyi D, Dzangare J, Nhachi CF. Acute oral toxicity and neurobehavioural toxicological effects of hydroethanolic extract of Boophone disticha in rats. Hum Exp Toxicol 2011;30:972-80.
  14. Pote W, Tagwireyi D, Chinyanga HM, Musara C, Pfukenyi DM, Nkomozepi P, Gadaga LL, Nyandoro G, Chifamba J. Long-term cardiovascular autonomic responses to aqueous ethanolic extract of Boophone disticha bulb in early maternally separated BALB/c mice. S Afr J Bot 2014;94:33-9.
  15. Pote W, Musarira S, Chuma D, Gadaga LL, Mwandiringana E, Tagwireyi D. Effects of a hydroethanolic extract of Boophone disticha bulb on anxiety-related behaviour in naive BALB/c mice. J Ethnopharmacol 2018;214:218-24.
  16. Pedersen ME, Szewczyk B, Stachowicz K, Wieronska J, Andersen J, Stafford GI, van Staden J, Pilc A, Jager AK. Effects of South African traditional medicine in animal models for depression. J Ethnopharmacol 2008;119:542-8.
  17. Cheesman L, Nair JJ, van Staden J. Antibacterial activity of crinane alkaloids from Boophone disticha (Amaryllidaceae). J Ethnopharmacol 2012;140:405-8.
  18. Nkomozepi P, Mazengenya P, Ihunwo AO. Age-related changes in Ki-67 and DCX expression in the BALB/ c mouse (Mus Musculus) brain. Int J Dev Neurosci 2019;72:36-47.
  19. Song NN, Huang Y, Yu X, Lang B, Ding YQ, Zhang L. Divergent roles of central serotonin in adult hippocampal neurogenesis. Front Cell Neurosci 2017;11:185.
  20. Malykhin NV, Coupland NJ. Hippocampal neuroplasticity in major depressive disorder. Neuroscience 2015;309:200-13.
  21. Mul JD, Zheng J, Goodyear LJ. Validity assessment of 5 day repeated forced-swim stress to model human depression in young-adult C57BL/6J and BALB/cJ mice. eNeuro 2016;3:ENEURO.0201-16.2016.
  22. Serchov T, Clement HW, Schwarz MK, Iasevoli F, Tosh DK, Idzko M, Jacobson KA, de Bartolomeis A, Normann C, Biber K, van Calker D. Increased signaling via adenosine A1 receptors, sleep deprivation, imipramine, and ketamine inhibit depressive-like behavior via induction of homer1a. Neuron 2015;87:549-62.
  23. Hodes GE, Hill-Smith TE, Lucki I. Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice. Neurosci Lett 2010;484:12-6.
  24. Pawluski JL, van Donkelaar E, Abrams Z, Houbart V, Fillet M, Steinbusch HW, Charlier TD. Fluoxetine dose and administration method differentially affect hippocampal plasticity in adult female rats. Neural Plast 2014;2014:123026.
  25. Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977;229:327-36.
  26. 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.
  27. PETA. Victories! PETA is ending near-drowning experiments on animals [Internet]. Norfolk, VA: People for the Ethical Treatment of Animals; c2020 [cited 2022 Jul 18]. Available from: https://www.peta.org/features/peta-ends-near-drowning-tests-small-animals.
  28. LASA. The forced swim test [Internet]. Hull: LASA; c2020 [cited 2022 Jul 22]. Available from: https://www.lasa.co.uk/the-forced-swim-test.
  29. Sewell F, Waterson I, Jones D, Tricklebank MD, Ragan I. Preclinical screening for antidepressant activity - shifting focus away from the Forced Swim Test to the use of translational biomarkers. Regul Toxicol Pharmacol 2021;125:105002.
  30. Nalloor R, Bunting K, Vazdarjanova A. Predicting impaired extinction of traumatic memory and elevated startle. PLoS One 2011;6:e19760.
  31. Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2007;2:322-8.
  32. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012;9:671-5.
  33. Zhang L, Li J, Lin A. Assessment of neurodegeneration and neuronal loss in aged 5XFAD mice. STAR Protoc 2021;2:100915.
  34. Neergaard JS, Andersen J, Pedersen ME, Stafford GI, Staden JV, Jager AK. Alkaloids from Boophone disticha with affinity to the serotonin transporter. S Afr J Bot 2009;75:371-4.
  35. Dulawa SC, Holick KA, Gundersen B, Hen R. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology 2004;29:1321-30.
  36. Mezadri TJ, Batista GM, Portes AC, Marino-Neto J, Lino-deOliveira C. Repeated rat-forced swim test: reducing the number of animals to evaluate gradual effects of antidepressants. J Neurosci Methods 2011;195:200-5.
  37. Detke MJ, Rickels M, Lucki I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology (Berl) 1995;121:66-72.
  38. Page ME, Detke MJ, Dalvi A, Kirby LG, Lucki I. Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology (Berl) 1999;147:162-7.
  39. Handley SL, McBlane JW. An assessment of the elevated X-maze for studying anxiety and anxiety-modulating drugs. J Pharmacol Toxicol Methods 1993;29:129-38.
  40. Rocher C, Spedding M, Munoz C, Jay TM. Acute stress-induced changes in hippocampal/prefrontal circuits in rats: effects of antidepressants. Cereb Cortex 2004;14:224-9. Erratum in: Cereb Cortex 2004;14:352.
  41. Lee T, Jarome T, Li SJ, Kim JJ, Helmstetter FJ. Chronic stress selectively reduces hippocampal volume in rats: a longitudinal magnetic resonance imaging study. Neuroreport 2009;20:1554-8.
  42. Malhi GS, Das P, Outhred T, Dobson-Stone C, Irwin L, Gessler D, Bryant R, Mannie Z. Effect of stress gene-by-environment interactions on hippocampal volumes and cortisol secretion in adolescent girls. Aust N Z J Psychiatry 2019;53:316-25.
  43. Moica T, Gligor A, Moica S. The relationship between cortisol and the hippocampal volume in depressed patients - a MRI pilot study. Proced Technol 2016;22:1106-12.
  44. Rahman MM, Callaghan CK, Kerskens CM, Chattarji S, O'Mara SM. Early hippocampal volume loss as a marker of eventual memory deficits caused by repeated stress. Sci Rep 2016;6:29127.
  45. Zimmerman ME, Ezzati A, Katz MJ, Lipton ML, Brickman AM, Sliwinski MJ, Lipton RB. Perceived stress is differentially related to hippocampal subfield volumes among older adults. PLoS One 2016;11:e0154530.
  46. Pham K, Nacher J, Hof PR, McEwen BS. Repeated restraint stress suppresses neurogenesis and induces biphasic PSANCAM expression in the adult rat dentate gyrus. Eur J Neurosci 2003;17:879-86.
  47. Mirescu C, Gould E. Stress and adult neurogenesis. Hippocampus 2006;16:233-8.
  48. Mareckova K, Marecek R, Bencurova P, Klanova J, Dusek L, Brazdil M. Perinatal stress and human hippocampal volume: findings from typically developing young adults. Sci Rep 2018;8:4696.
  49. Maguire EA, Woollett K, Spiers HJ. London taxi drivers and bus drivers: a structural MRI and neuropsychological analysis. Hippocampus 2006;16:1091-101.
  50. Leuner B, Gould E. Structural plasticity and hippocampal function. Annu Rev Psychol 2010;61:111-40, C1-3.
  51. Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T, Suzuki H. Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proc Natl Acad Sci U S A 2010;107:8434-9.
  52. Ohira K, Miyakawa T. Chronic treatment with fluoxetine for more than 6 weeks decreases neurogenesis in the subventricular zone of adult mice. Mol Brain 2011;4:10.
  53. Ohira K, Hagihara H, Miwa M, Nakamura K, Miyakawa T. Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset. Mol Brain 2019;12:69.
  54. Shuto T, Kuroiwa M, Sotogaku N, Kawahara Y, Oh YS, Jang JH, Shin CH, Ohnishi YN, Hanada Y, Miyakawa T, Kim Y, Greengard P, Nishi A. Obligatory roles of dopamine D1 receptors in the dentate gyrus in antidepressant actions of a selective serotonin reuptake inhibitor, fluoxetine. Mol Psychiatry 2020;25:1229-44.
  55. Encinas JM, Vaahtokari A, Enikolopov G. Fluoxetine targets early progenitor cells in the adult brain. Proc Natl Acad Sci U S A 2006;103:8233-8.
  56. Wang JW, David DJ, Monckton JE, Battaglia F, Hen R. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci 2008;28:1374-84.
  57. Boldrini M, Santiago AN, Hen R, Dwork AJ, Rosoklija GB, Tamir H, Arango V, John Mann J. Hippocampal granule neuron number and dentate gyrus volume in antidepressant-treated and untreated major depression. Neuropsychopharmacology 2013;38:1068-77.
  58. Samuels BA, Anacker C, Hu A, Levinstein MR, Pickenhagen A, Tsetsenis T, Madronal N, Donaldson ZR, Drew LJ, Dranovsky A, Gross CT, Tanaka KF, Hen R. 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response. Nat Neurosci 2015;18:1606-16.
  59. Turcotte-Cardin V, Vahid-Ansari F, Luckhart C, Daigle M, Geddes SD, Tanaka KF, Hen R, James J, Merali Z, Beique JC, Albert PR. Loss of adult 5-HT1A autoreceptors results in a paradoxical anxiogenic response to antidepressant treatment. J Neurosci 2019;39:1334-46.
  60. Klempin F, Babu H, De Pietri Tonelli D, Alarcon E, Fabel K, Kempermann G. Oppositional effects of serotonin receptors 5-HT1a, 2, and 2c in the regulation of adult hippocampal neurogenesis. Front Mol Neurosci 2010;3:14.
  61. Arnold SA, Hagg T. Serotonin 1A receptor agonist increases species- and region-selective adult CNS proliferation, but not through CNTF. Neuropharmacology 2012;63:1238-47.
  62. Mendez-David I, David DJ, Darcet F, Wu MV, Kerdine-Romer S, Gardier AM, Hen R. Rapid anxiolytic effects of a 5-HT4 receptor agonist are mediated by a neurogenesis-independent mechanism. Neuropsychopharmacology 2014;39:1366-78.
  63. Browne CA, Hanke J, Rose C, Walsh I, Foley T, Clarke G, Schwegler H, Cryan JF, Yilmazer-Hanke D. Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction. Stress 2014;17:471-83.
  64. Habr SF, Macrini DJ, Florio JC, Bernardi MM. Repeated forced swim stress has additive effects in anxiety behavior and in cathecolamine levels of adult rats exposed to deltamethrin. Neurotoxicol Teratol 2014;46:57-61.
  65. Gong S, Miao YL, Jiao GZ, Sun MJ, Li H, Lin J, Luo MJ, Tan JH. Dynamics and correlation of serum cortisol and corticosterone under different physiological or stressful conditions in mice. PLoS One 2015;10:e0117503.
  66. Wasinski F, Estrela GR, Arakaki AM, Bader M, Alenina N, Klempin F, Araujo RC. Maternal forced swimming reduces cell proliferation in the postnatal dentate gyrus of mouse offspring. Front Neurosci 2016;10:402.
  67. Emiliano S, Ana Cecilia L, Karen B, Guillermo H, Nancy R. Effect of prenatal stress and forced swimming acute stress on adult rat's skeletal muscle and liver MDA levels. MOJ Anat Physiol 2019;6:266-31.
  68. Safari MA, Koushkie Jahromi M, Rezaei R, Aligholi H, Brand S. The effect of swimming on anxiety-like behaviors and corticosterone in stressed and unstressed rats. Int J Environ Res Public Health 2020;17:6675.
  69. Aihara M, Ida I, Yuuki N, Oshima A, Kumano H, Takahashi K, Fukuda M, Oriuchi N, Endo K, Matsuda H, Mikuni M. HPA axis dysfunction in unmedicated major depressive disorder and its normalization by pharmacotherapy correlates with alteration of neural activity in prefrontal cortex and limbic/paralimbic regions. Psychiatry Res 2007;155:245-56.
  70. Knorr U, Vinberg M, Gether U, Winkel P, Gluud C, Wetterslev J, Kessing LV. The effect of escitalopram versus placebo on perceived stress and salivary cortisol in healthy first-degree relatives of patients with depression-a randomised trial. Psychiatry Res 2012;200:354-60.
  71. Hernandez ME, Mendieta D, Perez-Tapia M, Bojalil R, EstradaGarcia I, Estrada-Parra S, Pavon L. Effect of selective serotonin reuptake inhibitors and immunomodulator on cytokines levels: an alternative therapy for patients with major depressive disorder. Clin Dev Immunol 2013;2013:267871.
  72. Ruhe HG, Khoenkhoen SJ, Ottenhof KW, Koeter MW, Mocking RJ, Schene AH. Longitudinal effects of the SSRI paroxetine on salivary cortisol in Major Depressive Disorder. Psychoneuroendocrinology 2015;52:261-71.
  73. Inder WJ, Prickett TC, Mulder RT, Donald RA, Joyce PR. Reduction in basal afternoon plasma ACTH during early treatment of depression with fluoxetine. Psychopharmacology (Berl) 2001;156:73-8.
  74. Paile-Hyvarinen M, Wahlbeck K, Eriksson JG. Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: a single-blind randomised placebo controlled trial. BMC Fam Pract 2003;4:7.
  75. Hinkelmann K, Moritz S, Botzenhardt J, Muhtz C, Wiedemann K, Kellner M, Otte C. Changes in cortisol secretion during antidepressive treatment and cognitive improvement in patients with major depression: a longitudinal study. Psychoneuroendocrinology 2012;37:685-92.
  76. Aydemir O, Deveci A, Taneli F. The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:261-5.
  77. Castren E, Rantamaki T. The role of BDNF and its receptors in depression and antidepressant drug action: reactivation of developmental plasticity. Dev Neurobiol 2010;70:289-97.
  78. Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 2011;10:209-19.
  79. Guilloux JP, Douillard-Guilloux G, Kota R, Wang X, Gardier AM, Martinowich K, Tseng GC, Lewis DA, Sibille E. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol Psychiatry 2012;17:1130-42.
  80. Tripp A, Oh H, Guilloux JP, Martinowich K, Lewis DA, Sibille E. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. Am J Psychiatry 2012;169:1194-202.
  81. Wu LM, Hu MH, Tong XH, Han H, Shen N, Jin RT, Wang W, Zhou GX, He GP, Liu YS. Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF) in mouse ovaries: relationship to oocytes developmental potential. PLoS One 2012;7:e52331.
  82. Phillips C. Brain-derived neurotrophic factor, depression, and physical activity: making the neuroplastic connection. Neural Plast 2017;2017:7260130.
  83. Monteggia LM, Luikart B, Barrot M, Theobold D, Malkovska I, Nef S, Parada LF, Nestler EJ. Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biol Psychiatry 2007;61:187-97.
  84. Lindholm JS, Castren E. Mice with altered BDNF signaling as models for mood disorders and antidepressant effects. Front Behav Neurosci 2014;8:143.
  85. Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 1995;15:7539-47.
  86. Nibuya M, Nestler EJ, Duman RS. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 1996;16:2365-72.
  87. Maya Vetencourt JF, Sale A, Viegi A, Baroncelli L, De Pasquale R, O'Leary OF, Castren E, Maffei L. The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science 2008;320:385-8.
  88. Castren E. Neurotrophins and psychiatric disorders. Handb Exp Pharmacol 2014;220:461-79.
  89. Castren E, Kojima M. Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiol Dis 2017;97(Pt B):119-26.