Depressive disorders occur often jointly with anxiety disorders, which can cause serious health problems. The underlying mechanism is not fully understood. Figuring out the mechanism of depressive and anxiety disorders would benefit patients in future therapy. Brain-derived neurotrophic factor (BDNF) is a famous neurotrophin that modulates synaptic plasticity in the brain. It is generally believed that decreased BDNF levels are associated with depression. The purpose of this review is to elucidate the role of the BDNF-TrkB signaling pathway in different brain regions and its antidepressant effect, to provide scientific evidence for the treatment of anxiety and depression. The changes of the BDNF-TrkB signaling pathway before and after antidepressant treatment were compared by retrieving preclinical studies related to the BDNF-TrkB signaling pathway and classifying them according to different brain regions. It is found that the concentration of BDNF varies in different brain regions. The inhibition of the BDNF-TrkB pathway in the cortex, hippocampus, and amygdala and the activation of the BDNF-TrkB pathway in the anterior cingulate cortex (ACC), nucleus accumbens (NAc), and lateral habenula (LHb) is associated with anxiety and depression-like behaviors. Lacking BDNF or its receptor TrkB is not the cause of anxiety or depression, but affects the effect of antidepressant treatment. Increased BDNF can alleviate anxiety and depression. There are still other molecules that can regulate anxiety and depression-like behaviors by influencing the expression of BDNF or TrkB. The function of BDNF in the ACC, NAc, and LHb areas needs to be further explored.
| Published in | Clinical Neurology and Neuroscience (Volume 7, Issue 2) |
| DOI | 10.11648/j.cnn.20230702.11 |
| Page(s) | 18-30 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Depression, Anxiety, BDNF, TrkB, Mechanism, Pathway
| [1] | American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. |
| [2] | Helen Herrman, Vikram Patel, Christian Kieling, Michael Berk, Claudia Buchweitz, Pim Cuijpers, Toshiaki A Furukawa, Ronald C Kessler, Brandon A Kohrt, Mario Maj, Patrick McGorry, Charles F 3rd Reynolds, Myrna M Weissman, Dixon Chibanda, Christopher Dowrick, Louise M Howard, Christina W Hoven, Martin Knapp, Helen S Mayberg, Miranda Wolpert. (2022). Time for united action on depression: a Lancet-World Psychiatric Association Commission. Lancet, 399 (10328), 957-1022. doi: 10.1016/S0140-6736 (21)02141-3. |
| [3] | John W G Tiller. (2013). Depression and anxiety. Med J Aust, 199 (S6), S28-31. doi: 10.5694/mja12.10628. |
| [4] | G. B. D. Diseases, & Collaborators Injuries. (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. Lancet, 396 (10258), 1204-1222. doi: 10.1016/S0140-6736 (20)30925-9. |
| [5] | A J Ferrari, A J Somerville, A J Baxter, R Norman, S B Patten, T Vos, & H A Whiteford. (2013). Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. Psychol Med, 43 (3), 471-481. doi: 10.1017/S0033291712001511. |
| [6] | Jackson G Thorp, Zachary F Gerring, Lucia Colodro-Conde, Enda M Byrne, Sarah E Medland, Christel M Middeldorp, & Eske M Derks. (2023). The association between trauma exposure, polygenic risk and individual depression symptoms. Psychiatry Res, 321, 115101. doi: 10.1016/j.psychres.2023.115101. |
| [7] | Magdalena Gawrych, Ewelina Cichon, & Andrzej Kiejna. (2022). Depression among young adults - risks and protective factors in the COVID-19 pandemic. Postep Psychiatr Neurol, 31 (2), 52-61. doi: 10.5114/ppn.2022.118265. |
| [8] | Yuanyuan Xiao, Hailiang Ran, Die Fang, Yusan Che, Junwei Peng, Hao Sun, Xuemeng Liang, Lin Chen, Sifan Wang, & Jin Lu. (2022). Childhood maltreatment and depressive disorders in Chinese children and adolescents: A population-based case-control study. Asian J Psychiatr, 78, 103312. doi: 10.1016/j.ajp.2022.103312. |
| [9] | Covid- Mental Disorders Collaborators. (2021). Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet, 398 (10312), 1700-1712. doi: 10.1016/S0140-6736 (21) 02143-7. |
| [10] | Gabriel R Fries, Valeria A Saldana, Johannes Finnstein, & Theo Rein. (2023). Molecular pathways of major depressive disorder converge on the synapse. Mol Psychiatry, 28 (1), 284-297. doi: 10.1038/s41380-022-01806-1. |
| [11] | Yiyi Li, Fang Li, Dongdong Qin, Hongyu Chen, Jianhao Wang, Jiabei Wang, Shafei Song, Chao Wang, Yamei Wang, Songyan Liu, Dandan Gao, & Zhi-Hao Wang. (2022). The role of brain derived neurotrophic factor in central nervous system. Front Aging Neurosci, 14, 986443. doi: 10.3389/fnagi.2022.986443. |
| [12] | Daniele Cavaleri, Federico Moretti, Alessandra Bartoccetti, Stefano Mauro, Cristina Crocamo, Giuseppe Carra, & Francesco Bartoli. (2023). The role of BDNF in major depressive disorder, related clinical features, and antidepressant treatment: Insight from meta-analyses. Neurosci Biobehav Rev, 149, 105159. doi: 10.1016/j.neubiorev.2023.105159. |
| [13] | Mia Thompson Ray, Cynthia Shannon Weickert, Eugene Wyatt, & Maree J Webster. (2011). Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. J Psychiatry Neurosci, 36 (3), 195-203. doi: 10.1503/jpn.100048. |
| [14] | J-P Guilloux, G Douillard-Guilloux, R Kota, X Wang, A M Gardier, K Martinowich, G C Tseng, D A Lewis, & E. Sibille. (2012). Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol Psychiatry, 17 (11), 1130-1142. doi: 0.1038/mp.2011.113. |
| [15] | Giovanni Martinotti, Mauro Pettorruso, Domenico De Berardis, Paola Annunziata Varasano, Gabriella Lucidi Pressanti, Valeria De Remigis, Alessandro Valchera, Valerio Ricci, Marco Di Nicola, Luigi Janiri, Giovanni Biggio, & Massimo Di Giannantonio. (2016). Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms. Int J Neuropsychopharmacol, 19 (5). doi: 0.1093/ijnp/pyw003. |
| [16] | Luisella Bocchio-Chiavetto, Roberta Zanardini, Marco Bortolomasi, Maria Abate, Matilde Segala, Mario Giacopuzzi, Marco Andrea Riva, Eleonora Marchina, Patrizio Pasqualetti, Jorge Perez, & Massimo Gennarelli. (2006). Electroconvulsive Therapy (ECT) increases serum Brain Derived Neurotrophic Factor (BDNF) in drug resistant depressed patients. Eur Neuropsychopharmacol, 16 (8), 620-624. doi: 0.1016/j.euroneuro.2006.04.010. |
| [17] | B Chen, D Dowlatshahi, G M MacQueen, J F Wang, & L T Young. (2001). Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry, 50 (4), 260-265. doi: 0.1016/s0006-3223 (01)01083-6. |
| [18] | Zhiwei Guan, & Jidong Fang. (2006). Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats. Brain Behav Immun, 20 (1), 64-71. doi: 0.1016/j.bbi.2005.04.005. |
| [19] | C R Yang, Y Y Bai, C S Ruan, F H Zhou, F Li, C Q Li, & X F Zhou. (2017). Injection of Anti-proBDNF in Anterior Cingulate Cortex (ACC) Reverses Chronic Stress-Induced Adverse Mood Behaviors in Mice. Neurotox Res, 31 (2), 298-308. doi: 0.1007/s12640-016-9687-4. |
| [20] | M Nibuya, S Morinobu, & R S Duman. (1995). Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci, 15 (11), 7539-7547. doi: 0.1523/JNEUROSCI.15-11-07539.1995. |
| [21] | Yafei Ji, Jie Luo, Jiuseng Zeng, Yang Fang, Rong Liu, Fei Luan, & Nan Zeng. (2021). Xiaoyao Pills Ameliorate Depression-like Behaviors and Oxidative Stress Induced by Olfactory Bulbectomy in Rats via the Activation of the PIK3CA-AKT1-NFE2L2/BDNF Signaling Pathway. Front Pharmacol, 12, 643456. doi: 0.3389/fphar.2021.643456. |
| [22] | Indira Mendez-David, Laurent Tritschler, Zeina El Ali, Marie-Helene Damiens, Marc Pallardy, Denis J David, Saadia Kerdine-Romer, & Alain M Gardier. (2015). Nrf2-signaling and BDNF: A new target for the antidepressant-like activity of chronic fluoxetine treatment in a mouse model of anxiety/depression. Neurosci Lett, 597, 121-126. doi: 0.1016/j.neulet.2015.04.036. |
| [23] | Chun Yang, Yukihiko Shirayama, Ji-Chun Zhang, Qian Ren, & Kenji Hashimoto. (2015). Regional differences in brain-derived neurotrophic factor levels and dendritic spine density confer resilience to inescapable stress. Int J Neuropsychopharmacol, 18 (7), pyu121. doi: 0.1093/ijnp/pyu121. |
| [24] | Lucia Recinella, Annalisa Chiavaroli, Giustino Orlando, Claudio Ferrante, Serena Veschi, Alessandro Cama, Guya Diletta Marconi, Francesca Diomede, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew V Schally, Luigi Brunetti, & Sheila Leone. (2021). Effects of growth hormone-releasing hormone receptor antagonist MIA-602 in mice with emotional disorders: a potential treatment for PTSD. Mol Psychiatry, 26 (12), 7465-7474. doi: 0.1038/s41380-021-01228-5. |
| [25] | Ji-chun Zhang, Jin Wu, Yuko Fujita, Wei Yao, Qian Ren, Chun Yang, Su-xia Li, Yukihiko Shirayama, & Kenji Hashimoto. (2014). Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation. Int J Neuropsychopharmacol, 18 (4). doi: 0.1093/ijnp/pyu077. |
| [26] | Parvaneh Mohseni-Moghaddam, Manijeh Dogani, Motahare Hatami, Samira Roohollahi, Azam Amiresmaeli, & Nayereh Askari. (2022). A behavioral and molecular study; ameliorated anxiety-like behavior and cognitive dysfunction in a rat model of chronic unpredictable stress treated with oregano extract. Brain Behav, 12 (8), e2727. doi: 0.1002/brb3.2727. |
| [27] | Sinead M Gibney, Barry McGuinness, Christine Prendergast, Andrew Harkin, & Thomas J Connor. (2013). Poly I: C-induced activation of the immune response is accompanied by depression and anxiety-like behaviours, kynurenine pathway activation and reduced BDNF expression. Brain Behav Immun, 28, 170-181. doi: 0.1016/j.bbi.2012.11.010. |
| [28] | Qin Ru, Qi Xiong, Mei Zhou, Lin Chen, Xiang Tian, Huqiao Xiao, Chaoying Li, & Ying Li. (2019). Withdrawal from chronic treatment with methamphetamine induces anxiety and depression-like behavior in mice. Psychiatry Res, 271, 476-483. doi: 0.1016/j.psychres.2018.11.072. |
| [29] | Adnan Khan, Bushra Shal, Muhammad Naveed, Bakht Nasir, Nadeem Irshad, Hussain Ali, & Salman Khan. (2020). Matrine alleviates neurobehavioral alterations via modulation of JNK-mediated caspase-3 and BDNF/VEGF signaling in a mouse model of burn injury. Psychopharmacology (Berl), 237 (8), 2327-2343. doi: 0.1007/s00213-020-05537-5. |
| [30] | Basma Youssef, Kholoud S Ramadan, Shaimaa ElShebiney, & Ehab A Ibrahim. (2022). Antidepressant-like effects of aqueous extracts of miswak (Salvadora persica) and date palm (Phoenix dactylifera) on depression-like behaviors using CUMS model in male rats. J Food Biochem, 46 (8), e14164. doi: 0.1111/jfbc.14164. |
| [31] | Lanwei Hou, Yirui Qi, Hongwei Sun, Gang Wang, Qi Li, Yanyu Wang, Zuoji Zhang, Zhongde Du, & Lin Sun. (2018). Applying ketamine to alleviate the PTSD-like effects by regulating the HCN1-related BDNF. Prog Neuropsychopharmacol Biol Psychiatry, 86, 313-321. doi: 0.1016/j.pnpbp.2018.03.019. |
| [32] | Fei Guo, Bing Zhang, Zhiwen Fu, Yuqin Ma, Yu Gao, Fuyi Shen, Chenggang Huang, & Yang Li. (2016). The rapid antidepressant and anxiolytic-like effects of YY-21 involve enhancement of excitatory synaptic transmission via activation of mTOR signaling in the mPFC. Eur Neuropsychopharmacol, 26 (7), 1087-1098. doi: 0.1016/j.euroneuro.2016.05.006. |
| [33] | Chia-Yu Chang, How-Ran Guo, Wan-Chen Tsai, Kai-Lin Yang, Li-Chuan Lin, Tain-Junn Cheng, & Jiunn-Jye Chuu. (2015). Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression. Biomed Res Int, 2015, 159015. doi: 0.1155/2015/159015. |
| [34] | Raffaella Alo, Maria Mele, Gilda Fazzari, Ennio Avolio, & Marcello Canonaco. (2015). Exposure to sub-chronic unpredictable stress accounts for antidepressant-like effects in hamsters treated with BDNF and CNQX. Brain Res Bull, 118, 65-77. doi: 0.1016/j.brainresbull.2015.09.007. |
| [35] | P A Lapchak, D M Araujo, & F. Hefti. (1993). Systemic interleukin-1 beta decreases brain-derived neurotrophic factor messenger RNA expression in the rat hippocampal formation. Neuroscience, 53 (2), 297-301. doi: 0.1016/0306-4522 (93)90196-m. |
| [36] | Ying Yu, Zhaokun Shi, Dan Xu, Ying Li, Jun Qin, Zhaohui Zhang, & Hui Wang. (2020). Prenatal ethanol exposure increases susceptibility to depression- and anxiety-like behavior in adult female offspring and its underlying mechanism. Reprod Toxicol, 96, 36-46. doi: 0.1016/j.reprotox.2020.05.015. |
| [37] | Ga-Young Choi, Hyun-Bum Kim, Eun-Sang Hwang, Seok Lee, Min-Ji Kim, Ji-Young Choi, Sung-Ok Lee, Sang-Seong Kim, & Ji-Ho Park. (2017). Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats. Mediators Inflamm, 2017, 6280925. doi: 0.1155/2017/6280925. |
| [38] | Paulo Wagner Linhares Lima Filho, Adriano Jose Maia Chaves Filho, Charliene Freire Xavier Vieira, Tatiana de Queiroz Oliveira, Michelle Verde Ramo Soares, Paloma Marinho Juca, Joao Quevedo, Tatiana Barichello, Danielle Macedo, & Francisco das Chagas Medeiros. (2019). Peritoneal endometriosis induces time-related depressive- and anxiety-like alterations in female rats: involvement of hippocampal pro-oxidative and BDNF alterations. Metab Brain Dis, 34 (3), 909-925. doi: 0.1007/s11011-019-00397-1. |
| [39] | Haidar Tafner Curi, Clarissa Tavares Dias, Maria Laura Monteiro da Luz Camargo, Paula Dos Santos Gomez, Moises Felipe Pereira Gomes, Jose Ivo Araujo Beserra-Filho, Alessandra Medeiros, Alessandra Mussi Ribeiro, Fernando Moreira Simabuco, Rafael Herling Lambertucci, & Cristiano Mendes-da-Silva. (2021). Maternal high-fat diet increases anhedonic behavior and modulates hippocampal Mash1 and BDNF expression in adult offspring. Neurosci Lett, 764, 136239. doi: 0.1016/j.neulet.2021.136239. |
| [40] | Lorrane Kelle da Silva Moreira, Adriane Ferreira de Brito, Dayane Moreira da Silva, Lorrayne Siqueira, Daiany Priscilla Bueno da Silva, Carina Sofia Cardoso, Iziara Ferreira Florentino, Pablinny Moreira Galdino de Carvalho, Paulo Cesar Ghedini, Ricardo Menegatti, & Elson Alves Costa. (2021). Potential antidepressant-like effect of piperazine derivative LQFM212 in mice: Role of monoaminergic pathway and brain-derived neurotrophic factor. Behav Brain Res, 401, 113066. doi: 0.1016/j.bbr.2020.113066. |
| [41] | Arya Haj-Mirzaian, Shayan Amiri, Hossein Amini-Khoei, Mir-Jamal Hosseini, Arvin Haj-Mirzaian, Majid Momeny, Maryam Rahimi-Balaei, & Ahmad Reza Dehpour. (2017). Anxiety- and Depressive-Like Behaviors are Associated with Altered Hippocampal Energy and Inflammatory Status in a Mouse Model of Crohn's Disease. Neuroscience, 366, 124-137. doi: 0.1016/j.neuroscience.2017.10.023. |
| [42] | Xiaoyu Song, Bo Liu, Lingyu Cui, Biao Zhou, Weiwei Liu, Fanxing Xu, Toshihiko Hayashi, Shunji Hattori, Yuko Ushiki-Kaku, Shin-Ichi Tashiro, & Takashi Ikejima. (2017). Silibinin ameliorates anxiety/depression-like behaviors in amyloid beta-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus. Physiol Behav, 179, 487-493. doi: 0.1016/j.physbeh.2017.07.023. |
| [43] | Jie Liu, Chen Yang, Jing Yang, Xiaojie Song, Wei Han, Mingdan Xie, Li Cheng, Lingling Xie, Hengsheng Chen, & Li Jiang. (2019). Effects of early postnatal exposure to fine particulate matter on emotional and cognitive development and structural synaptic plasticity in immature and mature rats. Brain Behav, 9 (12), e01453. doi: 0.1002/brb3.1453. |
| [44] | Young-Ju Lee, Hye Ryeong Kim, Chang Youn Lee, Sung-Ae Hyun, Moon Yi Ko, Byoung-Seok Lee, Dae Youn Hwang, & Minhan Ka. (2020). 2-Phenylethylamine (PEA) Ameliorates Corticosterone-Induced Depression-Like Phenotype via the BDNF/TrkB/CREB Signaling Pathway. Int J Mol Sci, 21 (23). doi: 0.3390/ijms21239103. |
| [45] | Narmin Farazi, Javad Mahmoudi, Saeed Sadigh-Eteghad, Fereshteh Farajdokht, & Seyed Hossein Rasta. (2022). Synergistic effects of combined therapy with transcranial photobiomodulation and enriched environment on depressive- and anxiety-like behaviors in a mice model of noise stress. Lasers Med Sci, 37 (2), 1181-1191. doi: 0.1007/s10103-021-03370-6. |
| [46] | Pit Shan Chong, Chi Him Poon, Jaydeep Roy, Ka Chun Tsui, Sze Yuen Lew, Michael Weng Lok Phang, Rachael Julia Yuenyinn Tan, Poh Guat Cheng, Man-Lung Fung, Kah Hui Wong, & Lee Wei Lim. (2021). Neurogenesis-dependent antidepressant-like activity of Hericium erinaceus in an animal model of depression. Chin Med, 16 (1), 132. doi: 0.1186/s13020-021-00546-8. |
| [47] | Wen-Xue Liu, Jing Wang, Ze-Min Xie, Ning Xu, Guang-Fen Zhang, Min Jia, Zhi-Qiang Zhou, Kenji Hashimoto, & Jian-Jun Yang. (2016). Regulation of glutamate transporter 1 via BDNF-TrkB signaling plays a role in the anti-apoptotic and antidepressant effects of ketamine in chronic unpredictable stress model of depression. Psychopharmacology (Berl), 233 (3), 405-415. doi: 0.1007/s00213-015-4128-2. |
| [48] | Bo He, Dan Xu, Chong Zhang, Li Zhang, & Hui Wang. (2018). Prenatal food restriction induces neurobehavioral abnormalities in adult female offspring rats and alters intrauterine programming. Toxicol Res (Camb), 7 (2), 293-306. doi: 0.1039/c7tx00133a. |
| [49] | Tingxu Yan, Yingying Sun, Feng Xiao, Bo Wu, Kaishun Bi, Bosai He, & Ying Jia. (2019). Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain-derived neurotrophic factor. Phytother Res, 33 (12), 3177-3190. doi: 0.1002/ptr.6489. |
| [50] | Ayyub Babaei, Maryam Nourshahi, Maryam Fani, Zahra Entezari, Seyed Behnamedin Jameie, & Abbas Haghparast. (2021). The effectiveness of continuous and interval exercise preconditioning against chronic unpredictable stress: Involvement of hippocampal PGC-1alpha/FNDC5/BDNF pathway. J Psychiatr Res, 136, 173-183. doi: 0.1016/j.jpsychires.2021.02.006. |
| [51] | Julia M Rosa, Francis L Pazini, Gislaine Olescowicz, Anderson Camargo, Morgana Moretti, Joana Gil-Mohapel, & Ana Lucia S Rodrigues. (2019). Prophylactic effect of physical exercise on Abeta (1-40)-induced depressive-like behavior: Role of BDNF, mTOR signaling, cell proliferation and survival in the hippocampus. Prog Neuropsychopharmacol Biol Psychiatry, 94, 109646. doi: 0.1016/j.pnpbp.2019.109646. |
| [52] | Osamu Nakagawasai, Kotaro Yamada, Kohei Takahashi, Takayo Odaira, Wakana Sakuma, Daisuke Ishizawa, Naruya Takahashi, Kentaro Onuma, Chikako Hozumi, Wataru Nemoto, & Koichi Tan-No. (2020). Liver hydrolysate prevents depressive-like behavior in an animal model of colitis: Involvement of hippocampal neurogenesis via the AMPK/BDNF pathway. Behav Brain Res, 390, 112640. doi: 0.1016/j.bbr.2020.112640. |
| [53] | Payal Bajaj, & Gurcharan Kaur. (2022). Acute Sleep Deprivation-Induced Anxiety and Disruption of Hypothalamic Cell Survival and Plasticity: A Mechanistic Study of Protection by Butanol Extract of Tinospora cordifolia. Neurochem Res, 47 (6), 1692-1706. doi: 0.1007/s11064-022-03562-8. |
| [54] | Jing Wen, Yaowei Xu, Zhixiang Yu, Yifan Zhou, Wenting Wang, Jingjie Yang, Yiming Wang, Qian Bai, & Zhisong Li. (2022). The cAMP Response Element- Binding Protein/Brain-Derived Neurotrophic Factor Pathway in Anterior Cingulate Cortex Regulates Neuropathic Pain and Anxiodepression Like Behaviors in Rats. Front Mol Neurosci, 15, 831151. doi: 0.3389/fnmol.2022.831151. |
| [55] | Abimbola S Olugbemide, Benneth Ben-Azu, Adewale G Bakre, Abayomi M Ajayi, Omowumi Femi-Akinlosotu, & Solomon Umukoro. (2021). Naringenin improves depressive- and anxiety-like behaviors in mice exposed to repeated hypoxic stress through modulation of oxido-inflammatory mediators and NF-kB/BDNF expressions. Brain Res Bull, 169, 214-227. doi: 0.1016/j.brainresbull.2020.12.003. |
| [56] | Su Yeon Seo, Se Kyun Bang, Suk Yun Kang, Seong Jin Cho, Kwang Ho Choi, & Yeon Hee Ryu. (2021). Acupuncture Alleviates Anxiety and 22-kHz Ultrasonic Vocalizations in Rats Subjected to Repeated Alcohol Administration by Modulating the Brain-Derived Neurotrophic Factor/Corticotropin-Releasing Hormone Signaling Pathway. Int J Mol Sci, 22 (8). doi: 0.3390/ijms22084037. |
| [57] | Olivier Berton, Colleen A McClung, Ralph J Dileone, Vaishnav Krishnan, William Renthal, Scott J Russo, Danielle Graham, Nadia M Tsankova, Carlos A Bolanos, Maribel Rios, Lisa M Monteggia, David W Self, & Eric J Nestler. (2006). Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science, 311 (5762), 864-868. doi: 0.1126/science.1120972. |
| [58] | J A Siuciak, D R Lewis, S J Wiegand, & R M Lindsay. (1997). Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav, 56 (1), 131-137. doi: 0.1016/S0091-3057 (96)00169-4. |
| [59] | Ting Lei, Dan Dong, Meiying Song, Yanfei Sun, Xiaofeng Liu, & Hua Zhao. (2020). Rislenemdaz treatment in the lateral habenula improves despair-like behavior in mice. Neuropsychopharmacology, 45 (10), 1717-1724. doi: 0.1038/s41386-020-0652-9. |
| [60] | Mannan Abdul, Hao-Qi Yan, Wei-Nan Zhao, Xiao-Bin Lyu, Zheng Xu, Xiao-Lu Yu, Yi-Hong Gao, & Jun-Li Cao. (2022). VTA-NAc glutaminergic projection involves in the regulation of pain and pain-related anxiety. Front Mol Neurosci, 15, 1083671. doi: 0.3389/fnmol.2022.1083671. |
| [61] | Daniel C Lowes, Linda A Chamberlin, Lisa N Kretsge, Emma S Holt, Atheir I Abbas, Alan J Park, Lyubov Yusufova, Zachary H Bretton, Ayesha Firdous, Armen G Enikolopov, Joshua A Gordon, & Alexander Z Harris. (2021). Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice. Nat Commun, 12 (1), 3539. doi: 0.1038/s41467-021-23906-2. |
| [62] | Megumi Adachi, Anita E Autry, Melissa Mahgoub, Kanzo Suzuki, & Lisa M Monteggia. (2017). TrkB Signaling in Dorsal Raphe Nucleus is Essential for Antidepressant Efficacy and Normal Aggression Behavior. Neuropsychopharmacology, 42 (4), 886-894. doi: 0.1038/npp.2016.201. |
| [63] | Emily Ploppert, Joanna Jacob, Ana Deutsch, Sally Watanabe, Katherine Gillenwater, Alison Choe, George B Cruz, Ericka Cabanas, Michelle A Vasquez, Zaid Ayaz, Lorenz S Neuwirth, & Kelly Lambert. (2022). Influence of Effort-based Reward Training on Neuroadaptive Cognitive Responses: Implications for Preclinical Behavioral Approaches for Depressive Symptoms. Neuroscience, 500, 63-78. doi: 0.1016/j.neuroscience.2022.08.002. |
| [64] | M Kent, S Scott, S Lambert, E Kirk, B Terhune-Cotter, B Thompson, S Neal, B Dozier, M Bardi, & K. Lambert. (2018). Contingency Training Alters Neurobiological Components of Emotional Resilience in Male and Female Rats. Neuroscience, 386, 121-136. doi: 0.1016/j.neuroscience.2018.06.010. |
| [65] | Megumi Adachi, Michel Barrot, Anita E Autry, David Theobald, & Lisa M Monteggia. (2008). Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy. Biol Psychiatry, 63 (7), 642-649. doi: 0.1016/j.biopsych.2007.09.019. |
| [66] | Yukihiko Shirayama, Andrew C-H Chen, Shin Nakagawa, David S Russell, & Ronald S Duman. (2002). Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci, 22 (8), 3251-3261. doi: 0.1523/JNEUROSCI.22-08-03251.2002. |
| [67] | Amelia J Eisch, Carlos A Bolanos, Joris de Wit, Ryan D Simonak, Cindy M Pudiak, Michel Barrot, Joost Verhaagen, & Eric J Nestler. (2003). Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression. Biol Psychiatry, 54 (10), 994-1005. doi: 0.1016/j.biopsych.2003.08.003. |
| [68] | K R Jones, I Farinas, C Backus, & L F Reichardt. (1994). Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell, 76 (6), 989-999. doi: 0.1016/0092-8674 (94)90377-8. |
| [69] | Tommi Saarelainen, Panu Hendolin, Guilherme Lucas, Eija Koponen, Mikko Sairanen, Ewen MacDonald, Karin Agerman, Annakaisa Haapasalo, Hiroyuki Nawa, Raquel Aloyz, Patrik Ernfors, & Eero Castren. (2003). Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci, 23 (1), 349-357. doi: 0.1523/JNEUROSCI.23-01-00349.2003. |
| [70] | Lisa M Monteggia, Bryan Luikart, Michel Barrot, David Theobold, Irena Malkovska, Serge Nef, Luis F Parada, & Eric J Nestler. (2007). Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biol Psychiatry, 61 (2), 187-197. doi: 0.1016/j.biopsych.2006.03.021. |
| [71] | Lisa M Monteggia, Michel Barrot, Craig M Powell, Olivier Berton, Victor Galanis, Terry Gemelli, Sven Meuth, Andreas Nagy, Robert W Greene, & Eric J Nestler. (2004). Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci U S A, 101 (29), 10827-10832. doi: 0.1073/pnas.0402141101. |
| [72] | Keri Martinowich, Husseini Manji, & Bai Lu. (2007). New insights into BDNF function in depression and anxiety. Nat Neurosci, 10 (9), 1089-1093. doi: 0.1038/nn1971. |
| [73] | T Saarelainen, J A Lukkarinen, S Koponen, O H Grohn, J Jolkkonen, E Koponen, A Haapasalo, L Alhonen, G Wong, J Koistinaho, R A Kauppinen, & E. Castren. (2000). Transgenic mice overexpressing truncated trkB neurotrophin receptors in neurons show increased susceptibility to cortical injury after focal cerebral ischemia. Mol Cell Neurosci, 16 (2), 87-96. doi: 0.1006/mcne.2000.0863. |
| [74] | Xiao Zhuang, Bing Zhan, Yufeng Jia, Chaoze Li, Nan Wu, Ming Zhao, Nuo Chen, Yaxin Guo, Yingxin Du, Yi Zhang, Baihui Cao, Yan Li, Faliang Zhu, Chun Guo, Qun Wang, Yuan Li, & Lining Zhang. (2022). IL-33 in the basolateral amygdala integrates neuroinflammation into anxiogenic circuits via modulating BDNF expression. Brain Behav Immun, 102, 98-109. doi: 0.1016/j.bbi.2022.02.019. |
| [75] | O Guillin, J Diaz, P Carroll, N Griffon, J C Schwartz, & P. Sokoloff. (2001). BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Nature, 411 (6833), 86-89. doi: 0.1038/35075076. |
| [76] | Carolin Hoyer, Laura Kranaster, Alexander Sartorius, Rainer Hellweg, & Peter Gass. (2012). Long-term course of brain-derived neurotrophic factor serum levels in a patient treated with deep brain stimulation of the lateral habenula. Neuropsychobiology, 65 (3), 147-152. doi: 0.1159/000335243. |
| [77] | Yachun Wang, Peng Qu, Yimeng Sun, Ziang Li, Lei Liu, & Limin Yang. (2022). Association between increased inflammatory cytokine expression in the lateral habenular nucleus and depressive-like behavior induced by unpredictable chronic stress in rats. Exp Neurol, 349, 113964. doi: 0.1016/j.expneurol.2021.113964. |
| [78] | Peng Qu, Yachun Wang, Lei Liu, Mengmeng Qi, Yimeng Sun, Siyang Zheng, Zichen Xu, Changhong Liu, Xiaoyan Bai, Qinggao Zhang, & Limin Yang. (2020). Habenula lesions improve glucose metabolism in rats with type 2 diabetes by increasing insulin sensitivity and inhibiting gluconeogenesis. BMJ Open Diabetes Res Care, 8 (1). doi: 0.1136/bmjdrc-2020-001250. |
| [79] | Luciano Roman-Albasini, Gabriela Diaz-Veliz, Felipe Antonio Olave, Felipe Ignacio Aguayo, Gonzalo Garcia-Rojo, Wladimir Antonio Corrales, Juan Pablo Silva, Ana Maria Avalos, Paulina S Rojas, Esteban Aliaga, & Jenny Lucy Fiedler. (2020). Antidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats. Neurobiol Stress, 13, 100234. doi: 0.1016/j.ynstr.2020.100234. |
| [80] | Ya Li, Yajing Chen, Xiaoxiao Gao, & Zhongqiu Zhang. (2017). The behavioral deficits and cognitive impairment are correlated with decreased IGF-II and ERK in depressed mice induced by chronic unpredictable stress. Int J Neurosci, 127 (12), 1096-1103. doi: 0.1080/00207454.2017.1337014. |
| [81] | Yvfeng Liang, Jiahong Li, Tao Jin, Ting Gu, Qingjie Zhu, Yizhong Hu, Yang Yang, Jisui Li, Donghong Wu, Kesheng Jiang, & Xiaohong Xu. (2018). Bisphenol-A inhibits improvement of testosterone in anxiety- and depression-like behaviors in gonadectomied male mice. Horm Behav, 102, 129-138. doi: 0.1016/j.yhbeh.2018.05.012. |
| [82] | Xiaoli Qi, Wenjuan Lin, Donglin Wang, Yuqin Pan, Weiwen Wang, & Meng Sun. (2009). A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior. Behav Brain Res, 199 (2), 203-209. doi: 0.1016/j.bbr.2008.11.051. |
| [83] | Vittoria Borgonetti, Francisco Les, Victor Lopez, & Nicoletta Galeotti. (2020). Attenuation of Anxiety-Like Behavior by Helichrysum stoechas (L.) Moench Methanolic Extract through Up-Regulation of ERK Signaling Pathways in Noradrenergic Neurons. Pharmaceuticals (Basel), 13 (12). doi: 0.3390/ph13120472. |
| [84] | Zhen Wu, Pengyu Wang, Daodong Pan, Xiaoqun Zeng, Yuxing Guo, & Guangsheng Zhao. (2021). Effect of adzuki bean sprout fermented milk enriched in gamma-aminobutyric acid on mild depression in a mouse model. J Dairy Sci, 104 (1), 78-91. doi: 0.3168/jds.2020-19154. |
| [85] | Afzal Misrani, Sidra Tabassum, Xi Chen, Shu-Yi Tan, Ji-Chen Wang, Li Yang, & Cheng Long. (2019). Differential effects of citalopram on sleep-deprivation-induced depressive-like behavior and memory impairments in mice. Prog Neuropsychopharmacol Biol Psychiatry, 88, 102-111. doi: 0.1016/j.pnpbp.2018.07.013. |
| [86] | Gangadharan Thamizhoviya, & Arambakkam Janardhanam Vanisree. (2019). Enriched environment modulates behavior, myelination and augments molecules governing the plasticity in the forebrain region of rats exposed to chronic immobilization stress. Metab Brain Dis, 34 (3), 875-887. doi: 0.1007/s11011-018-0370-8. |
| [87] | Xian-Feng Huang, Wen-Tao Jiang, Li Liu, Fang-Chen Song, Xia Zhu, Gui-Lan Shi, Shu-Ming Ding, Heng-Ming Ke, Wei Wang, James M O'Donnell, Han-Ting Zhang, Hai-Bin Luo, Yi-Qian Wan, Guo-Qiang Song, & Ying Xu. (2018). A novel PDE9 inhibitor WYQ-C36D ameliorates corticosterone-induced neurotoxicity and depression-like behaviors by cGMP-CREB-related signaling. CNS Neurosci Ther, 24 (10), 889-896. doi: 0.1111/cns.12864. |
| [88] | Xi-Dan Zhou, Yu Zheng, Rakesh Sharma, & Zhang-Jin Zhang. (2019). Total Polysaccharides of Lily Bulb Ameliorate Menopause-Like Behavior in Ovariectomized Mice: Multiple Mechanisms Distinct from Estrogen Therapy. Oxid Med Cell Longev, 2019, 6869350. doi: 0.1155/2019/6869350. |
| [89] | Arindam Ghosh Mazumder, Pallavi Sharma, Vikram Patial, & Damanpreet Singh. (2017). Ginkgo biloba L. attenuates spontaneous recurrent seizures and associated neurological conditions in lithium-pilocarpine rat model of temporal lobe epilepsy through inhibition of mammalian target of rapamycin pathway hyperactivation. J Ethnopharmacol, 204, 8-17. doi: 0.1016/j.jep.2017.03.060. |
| [90] | Anfeng Wang, Xiaojuan Zou, Jiajia Wu, Qingyu Ma, Naijun Yuan, Fengmin Ding, Xiaojuan Li, & Jiaxu Chen. (2020). Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior. Front Genet, 11, 590068. doi: 0.3389/fgene.2020.590068. |
| [91] | Xiuping Sun, Xianglei Li, Ruile Pan, Yanfeng Xu, Qiong Wang, & Mingjing Song. (2018). Total Saikosaponins of Bupleurum yinchowense reduces depressive, anxiety-like behavior and increases synaptic proteins expression in chronic corticosterine-treated mice. BMC Complement Altern Med, 18 (1), 117. doi: 0.1186/s12906-018-2186-9. |
| [92] | Ju-Young Oh, Yu-Kang Kim, Seung-Nam Kim, Bombi Lee, Jae-Hwan Jang, Sunoh Kwon, & Hi-Joon Park. (2018). Acupuncture modulates stress response by the mTOR signaling pathway in a rat post-traumatic stress disorder model. Sci Rep, 8 (1), 11864. doi: 0.1038/s41598-018-30337-5. |
| [93] | Ju-Young Oh, Quan Feng Liu, Cai Hua, Ha Jin Jeong, Jae-Hwan Jang, Songhee Jeon, & Hi-Joon Park. (2020). Intranasal Administration of Melanin-Concentrating Hormone Reduces Stress-Induced Anxiety- and Depressive-Like Behaviors in Rodents. Exp Neurobiol, 29 (6), 453-469. doi: 0.5607/en20024. |
| [94] | Emilio Garro-Martinez, Maria Neus Fullana, Eva Florensa-Zanuy, Julia Senserrich, Veronica Paz, Esther Ruiz-Bronchal, Albert Adell, Elena Castro, Alvaro Diaz, Angel Pazos, Analia Bortolozzi, & Fuencisla Pilar-Cuellar. (2021). mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse. Int J Mol Sci, 22 (16). doi: 0.3390/ijms22168671. |
| [95] | Feini Zhou, Hao Jiang, Ning Kong, Jiangnan Lin, Fan Zhang, Ting Mai, Zhijian Cao, & Maosheng Xu. (2022). Electroacupuncture Attenuated Anxiety and Depression-Like Behavior via Inhibition of Hippocampal Inflammatory Response and Metabolic Disorders in TNBS-Induced IBD Rats. Oxid Med Cell Longev, 2022, 8295580. doi: 0.1155/2022/8295580. |
| [96] | Walaa Yehia Abdelzaher, Hanaa H Mohammed, Nermeen N Welson, Gaber El-Saber Batiha, Roua S Baty, & Asmaa Mohamed Abdel-Aziz. (2021). Rivaroxaban Modulates TLR4/Myd88/NF-Kbeta Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression. Front Pharmacol, 12, 715354. doi: 0.3389/fphar.2021.715354. |
| [97] | Xi Xiao, Hui Zhang, Wen Ning, Zhuo Yang, Yue Wang, & Tao Zhang. (2022). Knockdown of FSTL1 inhibits microglia activation and alleviates depressive-like symptoms through modulating TLR4/MyD88/NF-kappaB pathway in CUMS mice. Exp Neurol, 353, 114060. doi: 0.1016/j.expneurol.2022.114060. |
| [98] | Meng Wang, Li-Rong Feng, Zi-Long Li, Kai-Ge Ma, Ke-Wei Chang, Xin-Lin Chen, Peng-Bo Yang, Sheng-Feng Ji, Yan-Bing Ma, Hua Han, John Bosco Ruganzua, Wei-Na Yang, & Yi-Hua Qian. (2021). Thymosin beta4 reverses phenotypic polarization of glial cells and cognitive impairment via negative regulation of NF-kappaB signaling axis in APP/PS1 mice. J Neuroinflammation, 18 (1), 146. doi: 0.1186/s12974-021-02166-3. |
| [99] | Fernanda Severo Sabedra Sousa, Paloma Taborda Birmann, Suely Ribeiro Bampi, Mariana G Fronza, Renata Balaguez, Diego Alves, Marlon Regis Leite, Cristina Wayne Nogueira, Cesar Augusto Bruning, & Lucielli Savegnago. (2019). Lipopolysaccharide-induced depressive-like, anxiogenic-like and hyperalgesic behavior is attenuated by acute administration of alpha-(phenylselanyl) acetophenone in mice. Neuropharmacology, 146, 128-137. doi: 0.1016/j.neuropharm.2018.11.028. |
| [100] | Lea Decarie-Spain, Sandeep Sharma, Cecile Hryhorczuk, Victor Issa-Garcia, Philip A Barker, Nathalie Arbour, Thierry Alquier, & Stephanie Fulton. (2018). Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive sucrose seeking elicited by saturated dietary fat. Mol Metab, 10, 1-13. doi: 0.1016/j.molmet.2018.01.018. |
APA Style
Yafei Shi, Chunguang Mu, Yongjuan Xin. (2023). Role of BDNF-TrkB Signaling in Regulating Anxiety and Depression-Like Behavior in Diverse Brain Regions. Clinical Neurology and Neuroscience, 7(2), 18-30. https://doi.org/10.11648/j.cnn.20230702.11
ACS Style
Yafei Shi; Chunguang Mu; Yongjuan Xin. Role of BDNF-TrkB Signaling in Regulating Anxiety and Depression-Like Behavior in Diverse Brain Regions. Clin. Neurol. Neurosci. 2023, 7(2), 18-30. doi: 10.11648/j.cnn.20230702.11
AMA Style
Yafei Shi, Chunguang Mu, Yongjuan Xin. Role of BDNF-TrkB Signaling in Regulating Anxiety and Depression-Like Behavior in Diverse Brain Regions. Clin Neurol Neurosci. 2023;7(2):18-30. doi: 10.11648/j.cnn.20230702.11
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Download@article{10.11648/j.cnn.20230702.11,
author = {Yafei Shi and Chunguang Mu and Yongjuan Xin},
title = {Role of BDNF-TrkB Signaling in Regulating Anxiety and Depression-Like Behavior in Diverse Brain Regions},
journal = {Clinical Neurology and Neuroscience},
volume = {7},
number = {2},
pages = {18-30},
doi = {10.11648/j.cnn.20230702.11},
url = {https://doi.org/10.11648/j.cnn.20230702.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cnn.20230702.11},
abstract = {Depressive disorders occur often jointly with anxiety disorders, which can cause serious health problems. The underlying mechanism is not fully understood. Figuring out the mechanism of depressive and anxiety disorders would benefit patients in future therapy. Brain-derived neurotrophic factor (BDNF) is a famous neurotrophin that modulates synaptic plasticity in the brain. It is generally believed that decreased BDNF levels are associated with depression. The purpose of this review is to elucidate the role of the BDNF-TrkB signaling pathway in different brain regions and its antidepressant effect, to provide scientific evidence for the treatment of anxiety and depression. The changes of the BDNF-TrkB signaling pathway before and after antidepressant treatment were compared by retrieving preclinical studies related to the BDNF-TrkB signaling pathway and classifying them according to different brain regions. It is found that the concentration of BDNF varies in different brain regions. The inhibition of the BDNF-TrkB pathway in the cortex, hippocampus, and amygdala and the activation of the BDNF-TrkB pathway in the anterior cingulate cortex (ACC), nucleus accumbens (NAc), and lateral habenula (LHb) is associated with anxiety and depression-like behaviors. Lacking BDNF or its receptor TrkB is not the cause of anxiety or depression, but affects the effect of antidepressant treatment. Increased BDNF can alleviate anxiety and depression. There are still other molecules that can regulate anxiety and depression-like behaviors by influencing the expression of BDNF or TrkB. The function of BDNF in the ACC, NAc, and LHb areas needs to be further explored.},
year = {2023}
}
TY - JOUR T1 - Role of BDNF-TrkB Signaling in Regulating Anxiety and Depression-Like Behavior in Diverse Brain Regions AU - Yafei Shi AU - Chunguang Mu AU - Yongjuan Xin Y1 - 2023/07/06 PY - 2023 N1 - https://doi.org/10.11648/j.cnn.20230702.11 DO - 10.11648/j.cnn.20230702.11 T2 - Clinical Neurology and Neuroscience JF - Clinical Neurology and Neuroscience JO - Clinical Neurology and Neuroscience SP - 18 EP - 30 PB - Science Publishing Group SN - 2578-8930 UR - https://doi.org/10.11648/j.cnn.20230702.11 AB - Depressive disorders occur often jointly with anxiety disorders, which can cause serious health problems. The underlying mechanism is not fully understood. Figuring out the mechanism of depressive and anxiety disorders would benefit patients in future therapy. Brain-derived neurotrophic factor (BDNF) is a famous neurotrophin that modulates synaptic plasticity in the brain. It is generally believed that decreased BDNF levels are associated with depression. The purpose of this review is to elucidate the role of the BDNF-TrkB signaling pathway in different brain regions and its antidepressant effect, to provide scientific evidence for the treatment of anxiety and depression. The changes of the BDNF-TrkB signaling pathway before and after antidepressant treatment were compared by retrieving preclinical studies related to the BDNF-TrkB signaling pathway and classifying them according to different brain regions. It is found that the concentration of BDNF varies in different brain regions. The inhibition of the BDNF-TrkB pathway in the cortex, hippocampus, and amygdala and the activation of the BDNF-TrkB pathway in the anterior cingulate cortex (ACC), nucleus accumbens (NAc), and lateral habenula (LHb) is associated with anxiety and depression-like behaviors. Lacking BDNF or its receptor TrkB is not the cause of anxiety or depression, but affects the effect of antidepressant treatment. Increased BDNF can alleviate anxiety and depression. There are still other molecules that can regulate anxiety and depression-like behaviors by influencing the expression of BDNF or TrkB. The function of BDNF in the ACC, NAc, and LHb areas needs to be further explored. VL - 7 IS - 2 ER -
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