The antidepressant-like effect of NevGro® Forte in chronic unpredictable mild stress (CUMS) model of depression in rats
DOI:
https://doi.org/10.31117/neuroscirn.v6i4.261Keywords:
Depression, NevGro® Forte , Antidepressant, Neurogenesis, Chronic Unpredictable Mild Stress (CUMS)Abstract
Depression is a leading cause of disability worldwide and it is a major contributor to the overall global burden of disease. Almost 320 million individuals globally are left untreated with depression and it has the highest prevalence. Although there are multiple conventional antidepressant types available, patients are still left untreated due to inadequate pharmacological effectiveness as well as the high rate of remissions, side effects, and patients’ non-compliance. Therefore, this study aims to determine the therapeutic effects of NevGro® Forte. The NevGro® Forte that contains a combination of three types of mushrooms, Lignosus rhinocerotis, Ganoderma lucidum and Hericium erinaceus, has been reported to have the therapeutic potential for alleviating depressive symptoms. Sixty Sprague Dawley rats induced to chronic unpredictable mild stress (CUMS) protocol were orally treated with NevGro® Forte daily for 4 weeks. Histological analysis was performed to probe the role of neurogenesis in mediating the therapeutic effect of NevGro® Forte. Fluoxetine (FLX) was orally administered to validate the neurogenesis-dependent mechanism of NevGro® Forte. The present study exhibited that 4 weeks of NevGro® Forte treatment ameliorated the depressive symptoms in CUMS rat model. There is a significant improvement in body weight, brain’s weight, and increased thickness of the pyramidal layer in the hippocampus following the treatment of NevGro® Forte. Scanning electron microscopy also revealed decreased degeneration characterised by flattened with less dense surface composition in the hippocampus. This research shows a positive outcome of using NevGro® Forte in ameliorating depressive symptoms.
References
Adebiyi, O., Adigun, K., Folarin, O., Olopade, J., & Olayemi, F. (2020). Administration of ethanolic extract of Erythrophleum ivorense (A Chev.) stem bark to male Wistar rats alters brain areas involved in motor coordination, behavior, and memory. Journal of Ethnopharmacology, 253, 112650. https://doi.org/10.1016/j.jep.2020.112650
Ahmad, M. F. (2018). Ganoderma lucidum: Persuasive biologically active constituents and their health endorsement. Biomedicine & Pharmacotherapy, 107, 507–519. https://doi.org/10.1016/j.biopha.2018.08.036
Alemi, F., Min, H., Yousefi, M., Becker, L. K., Hane, C. A., Nori, V. S., & Wojtusiak, J. (2021). Effectiveness of common antidepressants: a post market release study. EClinical Medicine, 41, 101171. https://doi.org/10.1016/j.eclinm.2021.101171
Ali, S., Abd El Wahab, M., Ayuob, N., & Suliaman, M. (2017). The antidepressant-like effect of Ocimum basilicum in an animal model of depression. Biotechnic & Histochemistry, 92(6), 390–401. https://doi.org/10.1080/10520295.2017.1323276
American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). American Psychiatric Publishing.
Ayuob, N. N., & Balgoon, M. J. (2018). Histological and molecular techniques utilized to investigate animal models of depression. An updated review. Microscopy Research and Technique, 81(10), 1143–1153. https://doi.org/10.1002/jemt.23105
Ba, D. M., Gao, X., Al-Shaar, L., Muscat, J. E., Chinchilli, V. M., Beelman, R. B., & Richie, J. P. (2021). Mushroom intake and depression: A population-based study using data from the US National Health and Nutrition Examination Survey (NHANES), 2005–2016. Journal of Affective Disorders, 294, 686–692. https://doi.org/10.1016/j.jad.2021.07.080
Banasr, M., Dwyer, J. M., & Duman, R. S. (2011). Cell atrophy and loss in depression: reversal by antidepressant treatment. Current Opinion in Cell Biology, 23(6), 730–737. https://doi.org/10.1016/j.ceb.2011.09.002
Barch, D. M., Tillman, R., Kelly, D., Whalen, D., Gilbert, K., & Luby, J. L. (2019). Hippocampal volume and depression among young children. Psychiatry Research: Neuroimaging, 288, 21–28. https://doi.org/10.1016/j.pscychresns.2019.04.012
Benkert, O., Szegedi, A., & Kohnen, R. (2000). Mirtazapine compared with paroxetine in major depression. The Journal of Clinical Psychiatry, 61(9), 656–663. https://doi.org/10.4088/jcp.v61n0911
Beurel, E., Toups, M., & Nemeroff, C. B. (2020). The bidirectional relationship of depression and inflammation: double trouble. Neuron, 107(2), 234–256. https://doi.org/10.1016/j.neuron.2020.06.002
Bremner, J. D., Narayan, M., Anderson, E. R., Staib, L. H., Miller, H. L., & Charney, D. S. (2000). Hippocampal volume reduction in major depression. American Journal of Psychiatry, 157(1), 115–118. https://doi.org/10.1176/ajp.157.1.115
Burstein, O., & Doron, R. (2018). The unpredictable chronic mild stress protocol for inducing anhedonia in mice. Journal of Visualized Experiments, 140, e58184. https://doi.org/10.3791/58184
Cherubini, E., & Miles, R. (2015). The CA3 region of the hippocampus: how is it? What is it for? How does it do it? Frontiers in Cellular Neuroscience, 9, 19. https://doi.org/10.3389/fncel.2015.00019
Chong, P. S., Fung, M. L., Wong, K. H., & Lim, L. W. (2019). Therapeutic potential of hericium erinaceus for depressive disorder. International Journal of Molecular Sciences, 21(1), 163. https://doi.org/10.3390/ijms21010163
Chong, P. S., Poon, C. H., Roy, J., Tsui, K. C., Lew, S. Y., Phang, M. W. L., Tan, R. J. Y., Cheng, P. G., Fung, M. L., Wong, K. H., & Lim, L. W. (2021). Neurogenesis-dependent antidepressant-like activity of Hericium erinaceus in an animal model of depression. Chinese Medicine, 16(1), 132.
https://doi.org/10.1186/s13020-021-00546-8
Dhikav, V., & Anand, K. (2012). Hippocampus in health and disease: An overview. Annals of Indian Academy of Neurology, 15(4), 239. https://doi.org/10.4103/0972-2327.104323
Dudek, K. A., Dion‐Albert, L., Kaufmann, F. N., Tuck, E., Lebel, M., & Menard, C. (2019). Neurobiology of resilience in depression: immune and vascular insights from human and animal studies. European Journal of Neuroscience, 53(1), 183–221. https://doi.org/10.1111/ejn.14547
Frisbee, J. C., Brooks, S. D., Stanley, S. C., & D’Audiffret, A. C. (2015). An unpredictable chronic mild stress protocol for instigating depressive symptoms, behavioral changes and negative health outcomes in rodents. Journal of Visualized Experiments, 106, e53109. https://doi.org/10.3791/53109
Jonas, P., & Lisman, J. (2014). Structure, function, and plasticity of hippocampal dentate gyrus microcircuits. Frontiers in Neural Circuits, 8, 107. https://doi.org/10.3389/fncir.2014.00107
Kim, Y. K., & Park, S. C. (2021). An alternative approach to future diagnostic standards for major depressive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 105, 110133. https://doi.org/10.1016/j.pnpbp.2020.110133
Kittimongkolsuk, P., Pattarachotanant, N., Chuchawankul, S., Wink, M., & Tencomnao, T. (2021). Neuroprotective effects of extracts from tiger milk mushroom Lignosus rhinocerus against glutamate-induced toxicity in HT22 hippocampal neuronal cells and neurodegenerative diseases in Caenorhabditis elegans. Biology, 10(1), 30. https://doi.org/10.3390/biology10010030
Konttinen, H., van Strien, T., Männistö, S., Jousilahti, P., & Haukkala, A. (2019). Depression, emotional eating and long-term weight changes: a population-based prospective study. International Journal of Behavioral Nutrition and Physical Activity, 16(1), 28. https://doi.org/10.1186/s12966-019-0791-8
Lew, S. Y., Teoh, S. L., Lim, S. H., Lim, L. W., & Wong, K. H. (2020). Discovering the potentials of medicinal mushrooms in combating depression – A review. Mini-Reviews in Medicinal Chemistry, 20(15), 1518–1531. https://doi.org/10.2174/1389557520666200526125534
Liu, C., Gu, J. Y., Han, J. H., Yan, F. L., Li, Y., Lv, T. T., Zhao, L. Q., Shao, Q. J., Feng, Y. Y., Zhang, X. Y., & Wang, C. H. (2017). Enriched environment combined with fluoxetine ameliorates depression-like behaviors and hippocampal SYP expression in a rat CUS model. Brain Research Bulletin, 135, 33–39. https://doi.org/10.1016/j.brainresbull.2017.09.009
Meng, P., Zhu, Q., Yang, H., Liu, D., Lin, X., Liu, J., Fan, J., Liu, X., Su, W., Liu, L., Wang, Y., & Cai, X. (2019). Leonurine promotes neurite outgrowth and neurotrophic activity by modulating the GR/SGK1 signaling pathway in cultured PC12 cells. NeuroReport, 30(4), 247–254. https://doi.org/10.1097/wnr.0000000000001180
Micheli, L., Ceccarelli, M., D’Andrea, G., & Tirone, F. (2018). Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise. Brain Research Bulletin, 143, 181–193. https://doi.org/10.1016/j.brainresbull.2018.09.002
Niida, R., Yamagata, B., Matsuda, H., Niida, A., Uechi, A., Kito, S., & Mimura, M. (2018). Regional brain volume reductions in major depressive disorder and bipolar disorder: An analysis by voxel‐based morphometry. International Journal of Geriatric Psychiatry, 34(1), 186–192. https://doi.org/10.1002/gps.5009
Nolan, M., Roman, E., Nasa, A., Levins, K. J., O’Hanlon, E., O’Keane, V., & Willian Roddy, D. (2020). Hippocampal and amygdalar volume changes in major depressive disorder: A targeted review and focus on stress. Chronic Stress, 4, 247054702094455. https://doi.org/10.1177/2470547020944553
Park, L. T., & Zarate, C. A. (2019). Depression in the primary care setting. New England Journal of Medicine, 380(6), 559–568. https://doi.org/10.1056/nejmcp1712493
Patsalos, O., Keeler, J., Schmidt, U., Penninx, B. W. J. H., Young, A. H., & Himmerich, H. (2021). Diet, obesity, and depression: A systematic review. Journal of Personalized Medicine, 11(3), 176. https://doi.org/10.3390/jpm11030176
Planchez, B., Surget, A., & Belzung, C. (2019). Animal models of major depression: drawbacks and challenges. Journal of Neural Transmission, 126(11), 1383–1408. https://doi.org/10.1007/s00702-019-02084-y
Polesza k, E., Wośko, S., Sławińska, K., Wyska, E., Szopa, A., ŚWiąder, K., Wróbel, A., Szponar, J., Doboszewska, U., Wlaź, P., Wlaź, A., & Serefko, A. (2020). Influence of the endocannabinoid system on the antidepressant activity of bupropion and moclobemide in the behavioural tests in mice. Pharmacological Reports, 72(6), 1562–1572. https://doi.org/10.1007/s43440-020-00088-0
Qiao, H., An, S. C., Ren, W., & Ma, X. M. (2014). Progressive alterations of hippocampal CA3-CA1 synapses in an animal model of depression. Behavioural Brain Research, 275, 191–200. https://doi.org/10.1016/j.bbr.2014.08.040
Rădulescu, I., Drăgoi, A., Trifu, S., & Cristea, M. (2021). Neuroplasticity and depression: Rewiring the brain’s networks through pharmacological therapy (Review). Experimental and Therapeutic Medicine, 22(4). https://doi.org/10.3892/etm.2021.10565
Ryu, S., Kim, H. G., Kim, J. Y., Kim, S. Y., & Cho, K. O. (2018). Hericium erinaceus extract reduces anxiety and depressive behaviors by promoting hippocampal neurogenesis in the adult mouse brain. Journal of Medicinal Food, 21(2), 174–180. https://doi.org/10.1089/jmf.2017.4006
Santomauro, D. F., Mantilla Herrera, A. M., Shadid, J., Zheng, P., Ashbaugh, C., Pigott, D. M., Abbafati, C., Adolph, C., Amlag, J. O., Aravkin, A. Y., Bang-Jensen, B. L., Bertolacci, G. J., Bloom, S. S., Castellano, R., Castro, E., Chakrabarti, S., Chattopadhyay, J., Cogen, R. M., Collins, J. K., . . . Ferrari, A. J. (2021). Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. The Lancet, 398(10312), 1700–1712. https://doi.org/10.1016/s0140-6736(21)02143-7
Scheggi, S., De Montis, M. G., & Gambarana, C. (2018). Making sense of rodent models of anhedonia. International Journal of Neuropsychopharmacology, 21(11), 1049–1065. https://doi.org/10.1093/ijnp/pyy083
Tang, M., Huang, H., Li, S., Zhou, M., Liu, Z., Huang, R., Liao, W., Xie, P., & Zhou, J. (2019). Hippocampal proteomic changes of susceptibility and resilience to depression or anxiety in a rat model of chronic mild stress. Translational Psychiatry, 9(1), 260. https://doi.org/10.1038/s41398-019-0605-4
Umschweif, G., Greengard, P., & Sagi, Y. (2019). The dentate gyrus in depression. European Journal of Neuroscience, 53(1), 39–64. https://doi.org/10.1111/ejn.14640
Van Dijk, M. T., Cha, J., Semanek, D., Aw, N., Gameroff, M. J., Abraham, E., Wickramaratne, P. J., Weissman, M. M., Posner, J., & Talati, A. (2021). Altered dentate gyrus microstructure in individuals at high familial risk for depression predicts future symptoms. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 6(1), 50–58. https://doi.org/10.1016/j.bpsc.2020.06.006
Vrany, E. A., Hawkins, M. A., Wu, W., & Stewart, J. C. (2018). Depressive symptoms and weight loss behaviors in U.S. adults. Eating Behaviors, 29, 107–113. https://doi.org/10.1016/j.eatbeh.2018.03.006
Vos, T., Lim, S. S., Abbafati, C., Abbas, K. M., Abbasi, M., Abbasifard, M., Abbasi-Kangevari, M., Abbastabar, H., Abd-Allah, F., Abdelalim, A., Abdollahi, M., Abdollahpour, I., Abolhassani, H., Aboyans, V., Abrams, E. M., Abreu, L. G., Abrigo, M. R. M., Abu-Raddad, L. J., Abushouk, A. I., . . . Murray, C. J. L. (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet, 396(10258), 1204–1222. https://doi.org/10.1016/s0140-6736(20)30925-9
WHO. (2019). Depression. Retrieved October 21, 2023, from https://www.who.int/health-topics/depression#tab=tab_1
WHO. (2022, March 2). COVID-19 pandemic triggers 25% increase in prevalence of anxiety and depression worldwide. Retrieved October 21, 2023, from https://www.who.int/news/item/02-03-2022-covid-19-pandemic-triggers-25-increase-in-prevalence-of-anxiety-and-depression-worldwide
Wyska, E. (2019). Pharmacokinetic considerations for current state-of-the-art antidepressants. Expert Opinion on Drug Metabolism & Toxicology, 15(10), 831–847. https://doi.org/10.1080/17425255.2019.1669560
Zheng, R., Zhang, Y., Yang, Z., Han, S., & Cheng, J. (2021). Reduced brain gray matter volume in patients with first-episode major depressive disorder: A quantitative meta-analysis. Frontiers in Psychiatry, 12, 671348. https://doi.org/10.3389/fpsyt.2021.671348
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Copyright (c) 2023 Zakirah Zainal Abidin, Juwita Junit, Muhammad Danial Che Ramli, Syntyche Seow Ling Sing, Poh Guat Cheng, Zolkapli Eshak, Mohamad Anuar Ahad, Hussin Muhammad

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