Identification of a low–molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice
Open accessAbstract
The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) have emerged as key mediators in the pathophysiology of several mood disorders, including anxiety and depression. However, therapeutic compounds that interact with TrkB receptors have been difficult to develop. Using a combination of structure-based in silico screening and high-capacity functional assays in recombinant and neuronal cells, we identified a low-molecular weight TrkB ligand (ANA-12) that prevented activation of the receptor by BDNF with a high potency. ANA-12 showed direct and selective binding to TrkB and inhibited processes downstream of TrkB without altering TrkA and TrkC functions. KIRA-ELISA analysis demonstrated that systemic administration of ANA-12 to adult mice decreased TrkB activity in the brain without affecting neuronal survival. Mice administered ANA-12 demonstrated reduced anxiety- and depression-related behaviors on a variety of tests predictive of anxiolytic and antidepressant properties in humans. This study demonstrates that structure-based virtual screening strategy can be an efficient method for discovering potent TrkB-selective ligands that are active in vivo. We further propose that ANA-12 may be a valuable tool for studying BDNF/TrkB signaling and may constitute a lead compound for developing the next generation of therapeutic agents for the treatment of mood disorders.
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ANA-12 is a selective partial agonist developed by Cazorla et al. using structure-based in silico screening.
“ANA-12 is a selective partial agonist that was first developed by Carzola et al. in 2011 using a structure-based in silico screening (Cazorla et al. 2011).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Cazorla et al. 2011
The paper identifies ANA-12 as a selective TrkB antagonist, not a partial agonist (section on structure-based virtual screening; no page available). Its account of virtual screening and its TrkB-selectivity experiments support those parts of the sentence, but directly contradict its description of ANA-12’s activity. (LLM, conf=0.92)
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Experimental — accuracy not yet measuredBDNF stimulation increases neurite outgrowth in PC12 cells transfected with TrkB compared to non-treated cells.
“Indeed, when PC12 cells transfected with TrkB were stimulated with BDNF for 48 h, neurite outgrowth was increased compared to the non-treated cells (Cazorla et al. 2011).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Cazorla et al. 2011
ANA-12 is a low-molecular weight antagonist of TrkB that can induce anxiolytic and antidepressant properties.
“In their study, the authors identified a low-molecular weight antagonist of TrkB that could induce anxiolytic and antidepressant properties.”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Cazorla et al. 2011
TrkB antagonists could induce cell death, an issue that should be addressed when considering chronic treatment regimens.
“In spite of these interesting results, antagonists could also induce cell death, an issue that should be addressed when considering using these agents in chronic treatment regimens (Cazorla et al. 2011; Takemoto et al. 2015).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Cazorla et al. 2011
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Cites
Duan, Y., Wu, C., Chowdhury, S., Lee, M. C., Xiong, G., Zhang, W., Yang, R., Cieplak, P., Luo, R., Lee, T.-S., et al. (2003) · Journal of Computational Chemistry · doi:10.1002/jcc.10349 · Cited by 4,271 · see citing works
The tail suspension test: A new method for screening antidepressants in mice
Steru, L., Chermat, R., Thierry, B., & Simon, P. (1985) · Psychopharmacology · doi:10.1007/bf00428203 · Cited by 3,534 · see citing works
A Neurotrophic Model for Stress-Related Mood Disorders
Duman, R. S., & Monteggia, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.013 · Cited by 3,375 · see citing works
Behavioral despair in mice: a primary screening test for antidepressants.
Porsolt, R. D., Bertin, A., & Jalfre, M. (1977) · PubMed · Cited by 3,275 · see citing works
A Fast Flexible Docking Method using an Incremental Construction Algorithm
Rarey, M., Kramer, B., Lengauer, T., & Klebe, G. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0477 · Cited by 2,836 · see citing works
The use of a plus-maze to measure anxiety in the mouse
Lister, R. G. (1987) · Psychopharmacology · doi:10.1007/bf00177912 · Cited by 2,617 · see citing works
Krishnan, V., Han, M.-H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., LaPlant, Q., Graham, A., Lutter, M., Lagace, D. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.09.018 · Cited by 2,307 · see citing works
Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress
Berton, O., McClung, C. A., DiLeone, R. J., Krishnan, V., Renthal, W., Russo, S. J., Graham, D., Tsankova, N. M., Bolanos, C. A., Rios, M., et al. (2006) · Science · doi:10.1126/science.1120972 · Cited by 2,129 · see citing works
Neurotrophin signal transduction in the nervous system
Kaplan, D. R., & Miller, F. D. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00092-1 · Cited by 1,944 · see citing works
Assessing antidepressant activity in rodents: recent developments and future needs
Cryan, J. F., Markou, A., & Lucki, I. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(02)02017-5 · Cited by 1,551 · see citing works
Virtual screening of chemical libraries
Shoichet, B. K. (2004) · Nature · doi:10.1038/nature03197 · Cited by 1,425 · see citing works
Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior
Chen, Z.-Y., Jing, D., Bath, K. G., Ieraci, A., Khan, T., Siao, C.-J., Herrera, D. G., Toth, M., Yang, C., McEwen, B. S., et al. (2006) · Science · doi:10.1126/science.1129663 · Cited by 1,340 · see citing works
New insights into BDNF function in depression and anxiety
Martinowich, K., Manji, H., & Lu, B. (2007) · Nature Neuroscience · doi:10.1038/nn1971 · Cited by 1,221 · see citing works
BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis
Bramham, C. R., & Messaoudi, E. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.003 · Cited by 1,193 · see citing works
T-maze alternation in the rodent
Deacon, R. M. J., & Rawlins, J. N. P. (2006) · Nature Protocols · doi:10.1038/nprot.2006.2 · Cited by 901 · see citing works
Castrén, E., & Rantamäki, T. (2010) · Developmental Neurobiology · doi:10.1002/dneu.20758 · Cited by 864 · see citing works
p75 and Trk: A two-receptor system
Chao, M. V., & Hempstead, B. L. (1995) · Trends in Neurosciences · doi:10.1016/0166-2236(95)93922-k · Cited by 857 · see citing works
Early-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice
Ansorge, M. S., Zhou, M., Lira, A., Hen, R., & Gingrich, J. A. (2004) · Science · doi:10.1126/science.1101678 · Cited by 817 · see citing works
Saarelainen, T., Hendolin, P., Lucas, G., Koponen, E., Sairanen, M., MacDonald, E., Agerman, K., Haapasalo, A., Nawa, H., Aloyz, R., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00349.2003 · Cited by 800 · see citing works
BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory?
Lü, Y., Christian, K. M., & Lu, B. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.08.018 · Cited by 768 · see citing works
A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone
Jang, S., Liu, X., Yepes, M., Shepherd, K. R., Miller, G. W., Liu, Y., Wilson, W. D., Xiao, G., Blanchi, B., Sun, Y. E., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913572107 · Cited by 689 · see citing works
Mutant Mice and Neuroscience: Recommendations Concerning Genetic Background
Silva, A. J., Simpson, E. M., Takahashi, J. S., Lipp, H.-P., Nakanishi, S., Wehner, J. M., Giese, K. P., Tully, T., Abel, T., Chapman, P. F., et al. (1997) · Neuron · doi:10.1016/s0896-6273(00)80958-7 · Cited by 479 · see citing works
Parker, R. B., & Waud, D. R. (1971) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)28846-2 · Cited by 445 · see citing works
Eisch, A. J., Bolaños, C. A., de Wit, J., Simonak, R. D., Pudiak, C. M., Barrot, M., Verhaagen, J., & Nestler, E. J. (2003) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.08.003 · Cited by 420 · see citing works
Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents
Massa, S. M., Yang, T., Xie, Y., Shi, J., Bilgen, M., Joyce, J. N., Nehama, D., Rajadas, J., & Longo, F. M. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41356 · Cited by 406 · see citing works
Graham, D. L., Edwards, S., Bachtell, R. K., Dileone, R., Rios, M., & Self, D. W. (2007) · Nature Neuroscience · doi:10.1038/nn1929 · Cited by 401 · see citing works
The interplay of learning and anxiety in the elevated plus-maze
File, S. E. (1993) · Behavioural Brain Research · doi:10.1016/0166-4328(93)90103-w · Cited by 334 · see citing works
Green, S. H., Rydel, R. E., Connolly, J. L., & Greene, L. A. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.102.3.830 · Cited by 279 · see citing works
Bodnoff, S. R., Suranyi-Cadotte, B., Quirion, R., & Meaney, M. J. (1989) · Psychopharmacology · doi:10.1007/bf00442264 · Cited by 221 · see citing works
MacQUEEN, G. M., Ramakrishman, K., Croll, S. D., Siuciak, J. A., Yu, G., Young, T., & Fahnestock, M. L. (2001) · Behavioral Neuroscience · doi:10.1037/0735-7044.115.5.1145 · Cited by 212 · see citing works
Between a rock and a hard place?
Whitty, A., & Kumaravel, G. (2006) · Nature Chemical Biology · doi:10.1038/nchembio0306-112 · Cited by 170 · see citing works
Emerging themes in structural biology of neurotrophic factors
Ibáñez, C. F. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01266-1 · Cited by 163 · see citing works
Forebrain-specific trkB-receptor knockout mice: behaviorally more hyperactive than “depressive”
Zörner, B., Wolfer, D. P., Brandis, D., Kretz, O., Zacher, C., Madani, R., Kadow, I. C. G., Lipp, H., Klein, R., Henn, F. A., et al. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00418-9 · Cited by 145 · see citing works
BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine withdrawal
Pu, L., Liu, Q.-S., & Poo, M. (2006) · Nature Neuroscience · doi:10.1038/nn1687 · Cited by 133 · see citing works
Structure of the Brain-Derived Neurotrophic Factor/Neurotrophin 3 Heterodimer
Robinson, R. C., Radziejewski, C. H., Stuart, D. I., & Jones, E. Y. (1995) · Biochemistry · doi:10.1021/bi00013a001 · Cited by 125 · see citing works
Assessing the Scaffold Diversity of Screening Libraries
Krier, M., Bret, G., & Rognan, D. (2006) · Journal of Chemical Information and Modeling · doi:10.1021/ci050352v · Cited by 122 · see citing works
Self-citationCell death in regenerating populations of neurons in BDNF mutant mice
Linnarsson, S., Willson, C. A., & Ernfors, P. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00295-8 · Cited by 122 · see citing works
Fanous, S., Hammer, R. P., & Nikulina, E. M. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.02.064 · Cited by 118 · see citing works
A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats
Colangelo, A. M., Bianco, M. R., Vitagliano, L., Cavaliere, C., Cirillo, G., GIOIA, L. D., Diana, D., Colombo, D., Redaelli, C., Zaccaro, L., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5201-07.2008 · Cited by 116 · see citing works
Debeir, T., Saragovi, H. U., & Cuello, A. C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.4067 · Cited by 114 · see citing works
Specificity in Trk Receptor:Neurotrophin Interactions
Banfield, M. J., Naylor, R. L., Robertson, A., Allen, S. J., Dawbarn, D., & Brady, R. L. (2001) · Structure · doi:10.1016/s0969-2126(01)00681-5 · Cited by 113 · see citing works
Identification of Nonpeptide CCR5 Receptor Agonists by Structure-based Virtual Screening
Kellenberger, E., Springael, J., Parmentier, M., Hachet‐Haas, M., Galzi, J., & Rognan, D. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm061389p · Cited by 110 · see citing works
Self-citationNeurotrophin receptor structure and interactions
Yano, H., & Chao, M. V. (2000) · Pharmaceutica Acta Helvetiae · doi:10.1016/s0031-6865(99)00036-9 · Cited by 104 · see citing works
Cazorla, M., Jouvenceau, A., Rose, C., Guilloux, J.-P., Pilon, C., Dranovsky, A., & Prémont, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009777 · Cited by 99 · see citing works
Self-citationMolecular Basis of Neurotrophin−Receptor Interactions
Pattarawarapan, M., & Burgess, K. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm030221q · Cited by 85 · see citing works
Rashid, K., der Zee, C. E. V., Ross, G. M., Chapman, C. A., Stanisz, J., Rj, R., Racine, R. J., & Fahnestock, M. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.21.9495 · Cited by 70 · see citing works
Pardon, M., Roberts, R. E., Marsden, C. A., Bianchi, M., Latif, M. L., Duxon, M. S., & Kendall, D. A. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.01.033 · Cited by 60 · see citing works
The When and Where of BDNF and the Antidepressant Response
Wang, J., Dranovsky, A., & Hen, R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.01.008 · Cited by 55 · see citing works
Synthesis and amnesia-reversal activity of a series of 7- and 5-membered 3-acylamino lactams
Angelucci, L., Calvisi, P., Catini, R., Cosentino, U., Cozzolino, R., Witt, P. D., Ghirardi, O., Giannessi, F., & Giuliani, A. (1993) · Journal of Medicinal Chemistry · doi:10.1021/jm00063a001 · Cited by 12 · see citing works
Flagged first, then by citations
1 of the 50 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Psychedelics promote structural and functional neural plasticity
Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., Burbach, K. F., Soltanzadeh Zarandi, S., Sood, A., Paddy, M. R., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.05.022 · Cited by 1,207 · see citing works
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects
Yang, C., Shirayama, Y., Zhang, J.-C., Ren, Q., Yao, W., Ma, M., Dong, C., & Hashimoto, K. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.136 · Cited by 605 · see citing works
Zhang, J.-C., Yao, W., & Hashimoto, K. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666160119094646 · Cited by 538 · see citing works
Moylan, S., Maes, M., Wray, N. R., & Berk, M. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.33 · Cited by 529 · see citing works
Epigenetic inheritance of a cocaine-resistance phenotype
Vassoler, F. M., White, S., Schmidt, H. D., Sadri‐Vakili, G., & Pierce, R. C. (2012) · Nature Neuroscience · doi:10.1038/nn.3280 · Cited by 419 · see citing works
A leptin–BDNF pathway regulating sympathetic innervation of adipose tissue
Wang, P., Loh, K. H., Wu, M., Morgan, D. A., Schneeberger, M., Yu, X., Chi, J., Kosse, C., Kim, D., Rahmouni, K., et al. (2020) · Nature · doi:10.1038/s41586-020-2527-y · Cited by 332 · see citing works
Okamura, R., Boichard, A., Kato, S., Sicklick, J. K., Bazhenova, L., & Kurzrock, R. (2018) · JCO Precision Oncology · doi:10.1200/po.18.00183 · Cited by 328 · see citing works
Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression
Levy, M. J. F., Boulle, F., Steinbusch, H. W., van den Hove, D. L. A., Kenis, G., & Lanfumey, L. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4950-4 · Cited by 308 · see citing works
Longo, F. M., & Massa, S. M. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4024 · Cited by 294 · see citing works
Zhang, J.-C., Wu, J., Fujita, Y., Yao, W., Ren, Q., Yang, C., Li, S.-X., Shirayama, Y., & Hashimoto, K. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu077 · Cited by 289 · see citing works
Epigenetic Regulation of the BDNF Gene: Implications for Psychiatric Disorders
Boulle, F., van den Hove, D. L. A., Jakob, S. B., Rutten, B. P., Hamon, M., van Os, J., Lesch, K.-P., Lanfumey, L., Steinbusch, H. W., & Kenis, G. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.107 · Cited by 282 · see citing works
Podda, M. V., Cocco, S., Mastrodonato, A., Fusco, S., Leone, L., Barbati, S. A., Colussi, C., Ripoli, C., & Grassi, C. (2016) · Scientific Reports · doi:10.1038/srep22180 · Cited by 249 · see citing works
Ajdary, R., Tardy, B. L., Mattos, B. D., Bai, L., & Rojas, O. J. (2020) · Advanced Materials · doi:10.1002/adma.202001085 · Cited by 242 · see citing works
Neuroprotective strategies for retinal disease
Pardue, M. T., & Allen, R. S. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.02.002 · Cited by 237 · see citing works
Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs
Dale, E., Bang‐Andersen, B., & Sánchez, C. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.03.011 · Cited by 238 · see citing works
The Concise Guide to PHARMACOLOGY 2013/14: Catalytic Receptors
Alexander, S. P. H., Benson, H. E., Faccenda, E., Pawson, A. J., Sharman, J. L., Spedding, M., Peters, J. A., Harmar, A. J., & Collaborators, C. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12449 · Cited by 220 · see citing works
Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway
Walsh, J. J., Friedman, A. K., Sun, H., Heller, E. A., Ku, S. M., Juarez, B., Burnham, V. L., Mazei-Robison, M. S., Ferguson, D., Golden, S. A., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3591 · Cited by 210 · see citing works
Hashimoto, K. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.09.001 · Cited by 208 · see citing works
Fukumoto, K., Fogaça, M. V., Liu, R.-J., Duman, C., Kato, T., Li, X.-Y., & Duman, R. S. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814709116 · Cited by 188 · see citing works
Zhang, J.-C., Yao, W., Dong, C., Yang, C., Ren, Q., Ma, M., Han, M., & Hashimoto, K. (2015) · Psychopharmacology · doi:10.1007/s00213-015-4062-3 · Cited by 183 · see citing works
Ding, H., Chen, J., Su, M., Lin, Z., Zhan, H., Yang, F., Li, W., Xie, J., Huang, Y. L., Liu, X., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1704-0 · Cited by 162 · see citing works
Yang, J.-L., Lin, Y.-T., Chuang, P.-C., Bohr, V. A., & Mattson, M. P. (2014) · NeuroMolecular Medicine · doi:10.1007/s12017-013-8270-x · Cited by 159 · see citing works
Yao, W., Zhang, J.-C., Ishima, T., Dong, C., Yang, C., Ren, Q., Ma, M., Han, M., Wu, J., Suganuma, H., et al. (2016) · Scientific Reports · doi:10.1038/srep30659 · Cited by 154 · see citing works
STAT3–BDNF–TrkB signalling promotes alveolar epithelial regeneration after lung injury
Paris, A. J., Hayer, K. E., Oved, J. H., Avgousti, D. C., Toulmin, S. A., Zepp, J. A., Zacharias, W. J., Katzen, J. B., Basil, M. C., Kremp, M. M., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0569-x · Cited by 148 · see citing works
Lawn, S. O., Krishna, N., Pisklakova, A., Qu, X., Fenstermacher, D. A., Fournier, M., Vrionis, F. D., Tran, N., Chan, J. A.-W., Kenchappa, R. S., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.599373 · Cited by 141 · see citing works
Shirayama, Y., Yang, C., Zhang, J.-C., Ren, Q., Yao, W., & Hashimoto, K. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.09.002 · Cited by 137 · see citing works
Fan, D., Li, J., Zheng, B., Hua, L., & Zuo, Z. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-9013-1 · Cited by 127 · see citing works
Transient stimulation with psychoplastogens is sufficient to initiate neuronal growth
Ly, C., Greb, A. C., Vargas, M. V., Duim, W. C., Grodzki, A. C. G., Lein, P. J., & Olson, D. E. (2021) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.0c00065 · Cited by 123 · see citing works
Ghosal, S., Bang, E., Yue, W., Hare, B. D., Lepack, A. E., Girgenti, M. J., & Duman, R. S. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.06.017 · Cited by 111 · see citing works
The Pharmacology of Nociceptor Priming
Kandasamy, R., & Price, T. J. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-662-46450-2_2 · Cited by 107 · see citing works
BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals
Chen, W., Walwyn, W. M., Ennes, H. S., Kim, H. Y., McRoberts, J. A., & Marvizón, J. C. G. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12516 · Cited by 100 · see citing works
Ren, Q., Ma, M., Yang, C., Zhang, J.-C., Yao, W., & Hashimoto, K. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.157 · Cited by 99 · see citing works
Receptor Tyrosine Kinase Signaling and Targeting in Glioblastoma Multiforme
Tilak, M., Holborn, J., New, L. A., Lalonde, J., & Jones, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041831 · Cited by 99 · see citing works
TRiC subunits enhance BDNF axonal transport and rescue striatal atrophy in Huntington’s disease
Zhao, X., Chen, X., Han, E. K., Hu, Y., Paik, P. K., Ding, Z., Overman, J., Lau, A., Shahmoradian, S. H., Chiu, W., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1603020113 · Cited by 98 · see citing works
Bath, K. G., Chuang, J., Spencer-Segal, J. L., Amso, D., Altemus, M. M., McEwen, B. S., & Lee, F. S. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.03.032 · Cited by 94 · see citing works
Melemedjian, O. K., Tillu, D. V., Asiedu, M. N., Mandell, E. K., Moy, J. K., Blute, V. M., Taylor, C. J., Ghosh, S., & Price, T. J. (2013) · Molecular Pain · doi:10.1186/1744-8069-9-12 · Cited by 91 · see citing works
Zhang, G., Zhang, T., Li, N., Wu, L., Gu, J., Li, C., Zhao, C., Liu, W., Shan, L., Yu, P., et al. (2017) · British Journal of Pharmacology · doi:10.1111/bph.14102 · Cited by 90 · see citing works
Greenberg, G. D., Laman-Maharg, A., Campi, K. L., Voigt, H., Orr, V. N., Schaal, L., & Trainor, B. C. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00223 · Cited by 89 · see citing works
Chrysostomou, V., Galić, S., van Wijngaarden, P., Trounce, I. A., Steinberg, G. R., & Crowston, J. G. (2016) · Aging Cell · doi:10.1111/acel.12512 · Cited by 88 · see citing works
Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis
Sinkevicius, K. W., Kriegel, C., Bellaria, K. J., Lee, J. J., Lau, A. N., Leeman, K. T., Zhou, P., Beede, A. M., Brainson, C. F., Caswell, D. R., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404399111 · Cited by 87 · see citing works
Tau-Driven Neuronal and Neurotrophic Dysfunction in a Mouse Model of Early Tauopathy
Mazzaro, N., Barini, E., Spillantini, M. G., Goedert, M., Medini, P., & Gasparini, L. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0774-15.2016 · Cited by 86 · see citing works
Aerobic Exercise Protects Retinal Function and Structure from Light-Induced Retinal Degeneration
Lawson, E. C., Han, M. K., Sellers, J. T., Chrenek, M. A., Hanif, A. M., Gogniat, M. A., Boatright, J. H., & Pardue, M. T. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2062-13.2014 · Cited by 84 · see citing works
Sun, H.-L., Zhou, Z.-Q., Zhang, G.-F., Yang, C., Wang, X.-M., Shen, J.-C., Hashimoto, K., & Yang, J.-J. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.21 · Cited by 84 · see citing works
Zimmermann, K. S., Yamin, J. A., Rainnie, D. G., Ressler, K. J., & Gourley, S. L. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.10.026 · Cited by 78 · see citing works
Emili, M., Guidi, S., Uguagliati, B., Giacomini, A., Bartesaghi, R., & Stagni, F. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1810625 · Cited by 82 · see citing works
TrkB inhibition as a therapeutic target for CNS-related disorders
Boulle, F., Kenis, G., Cazorla, M., Hamon, M., Steinbusch, H. W. M., Lanfumey, L., & van den Hove, D. L. A. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.06.002 · Cited by 80 · see citing works
Self-citationBrain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice
Stragier, E., Martin, V., Davenas, E., Poilbout, C., Mongeau, R., Corradetti, R., & Lanfumey, L. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.183 · Cited by 80 · see citing works
Neuronal K+-Cl- cotransporter KCC2 as a promising drug target for epilepsy treatment
McMoneagle, E., Zhou, J. Q., Zhang, S., Huang, W., Josiah, S. S., Ding, K., Wang, Y., & Zhang, J. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01149-9 · Cited by 78 · see citing works
Targeting the BDNF/TrkB pathway for the treatment of tumors (Review)
Meng, L., Liu, B., Ji, R., Jiang, X. M., Yan, X., & Xin, Y. (2018) · Oncology Letters · doi:10.3892/ol.2018.9854 · Cited by 75 · see citing works
Kishi, T., Hirooka, Y., Nagayama, T., Isegawa, K., Katsuki, M., Takesue, K., & Sunagawa, K. (2014) · International Heart Journal · doi:10.1536/ihj.14-168 · Cited by 75 · see citing works
Yan, T., He, B., Wan, S., Xu, M., Yang, H., Xiao, F., Bi, K., & Jia, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-07407-1 · Cited by 75 · see citing works
Wang, T., Martin, S., Nguyen, T. H., Harper, C. B., Gormal, R. S., Martínez‐Mármol, R., Karunanithi, S., Coulson, E. J., Glass, N. R., Cooper-White, J. J., et al. (2016) · Nature Communications · doi:10.1038/ncomms12976 · Cited by 74 · see citing works
Briz, V., Liu, Y., Zhu, G., Bi, X., & Baudry, M. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201504092 · Cited by 72 · see citing works
FTY720/Fingolimod Reduces Synucleinopathy and Improves Gut Motility in A53T Mice
Vidal-Martínez, G., Vargas‐Medrano, J., Gil-Tommee, C., Medina, D. X., Garza, N. T., Yang, B. C., Segura‐Ulate, I., Dominguez, S. J., & Perez, R. G. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.744029 · Cited by 72 · see citing works
Psychedelics as a novel approach to treating autoimmune conditions
Thompson, C., & Szabó, A. (2020) · Immunology Letters · doi:10.1016/j.imlet.2020.10.001 · Cited by 71 · see citing works
Schmauss, C. (2015) · Scientific Reports · doi:10.1038/srep08171 · Cited by 71 · see citing works
Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor
Eddings, C. R., Arbez, N., Akimov, S., Geva, M., Hayden, M. R., & Ross, C. A. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.05.009 · Cited by 70 · see citing works
Exenatide exerts cognitive effects by modulating the BDNF-TrkB neurotrophic axis in adult mice
Bomba, M., Granzotto, A., Castelli, V., Massetti, N., Silvestri, E., Canzoniero, L. M. T., Cimini, A., & Sensi, S. L. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.12.009 · Cited by 69 · see citing works
Inhibition of neuronal FLT3 receptor tyrosine kinase alleviates peripheral neuropathic pain in mice
Rivat, C., Sar, C., Méchaly, I., Leyris, J.-P., Diouloufet, L., Sonrier, C., Philipson, Y., Lucas, O., Mallié, S., Jouvenel, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03496-2 · Cited by 69 · see citing works
Self-citationHsu, C., Kuo, T., Liu, W., Chang, C., & Lin, H. (2020) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09903-9 · Cited by 68 · see citing works
Melatonin protects inner retinal neurons of newborn mice after hypoxia‐ischemia
Huang, R., Xu, Y., Lü, X., Tang, X., Lin, J., Cui, K., Yu, S., Shi, Y., Ye, D., Liu, Y., et al. (2021) · Journal of Pineal Research · doi:10.1111/jpi.12716 · Cited by 67 · see citing works
Kishi, T., Hirooka, Y., & Sunagawa, K. (2012) · Journal of Cardiology · doi:10.1016/j.jjcc.2012.08.004 · Cited by 67 · see citing works
Yu, T.-H., Wu, Y., Chien, M.-E., & Hsu, K. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.11.012 · Cited by 65 · see citing works
Cannavò, A., Jun, S., Rengo, G., Marzano, F., Agrimi, J., Liccardo, D., Elia, A., Keceli, G., Altobelli, G. G., Marcucci, L., et al. (2023) · Circulation Research · doi:10.1161/circresaha.122.321583 · Cited by 65 · see citing works
Nomura, T., Musial, T. F., Marshall, J. J., Zhu, Y., Remmers, C. L., Xu, J., Nicholson, D. A., & Contractor, A. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2893-16.2017 · Cited by 64 · see citing works
Is neurotrophin-3 (NT-3): a potential therapeutic target for depression and anxiety?
de Miranda, A. S., de Barros, J. L. V. M., & Teixeira, A. L. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1846720 · Cited by 64 · see citing works
Solana‐Balaguer, J., Campoy‐Campos, G., Martín‐Flores, N., Pérez‐Sisqués, L., Sitjà‐Roqueta, L., Küçükerden, M., Gámez‐Valero, A., Coll‐Manzano, A., Martı́, E., Pérez‐Navarro, E., et al. (2023) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12355 · Cited by 64 · see citing works
Zhang, J.-C., Yao, W., Ren, Q., Yang, C., Dong, C., Ma, M., Wu, J., & Hashimoto, K. (2016) · Scientific Reports · doi:10.1038/srep36705 · Cited by 64 · see citing works
Saba, J., Turati, J., Ramírez, D., Carniglia, L., Durand, D., Lasaga, M., & Caruso, C. M. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14476 · Cited by 63 · see citing works
Ambrogini, P., Lattanzi, D., Ciuffoli, S., Betti, M., Fanelli, M., & Cuppini, R. (2013) · Brain Research · doi:10.1016/j.brainres.2013.08.023 · Cited by 61 · see citing works
Ma, M., Ren, Q., Yang, C., Zhang, J.-C., Yao, W., Dong, C., Ohgi, Y., Futamura, T., & Hashimoto, K. (2016) · Scientific Reports · doi:10.1038/srep39209 · Cited by 58 · see citing works
Ethanol-induced epigenetic regulations at the Bdnf gene in C57BL/6J mice
Stragier, E., Massart, R., Salery, M., Hamon, M., Gény, D., Martin, V., Boulle, F., & Lanfumey, L. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.38 · Cited by 59 · see citing works
Li, W., Su, X., Hu, N.-Y., Hu, J., Li, X., Yang, J., & Gao, T. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.04.019 · Cited by 61 · see citing works
Dopamine D3 Receptor Is Necessary for Ethanol Consumption: An Approach with Buspirone
Leggio, G. M., Camillieri, G., Platania, C. B. M., Castorina, A., Marrazzo, G., Torrisi, S. A., Nona, C. N., D’Agata, V., Nóbrega, J. N., Stark, H., et al. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.51 · Cited by 58 · see citing works
Burgos-Vega, C., Quigley, L. D., Avona, A., Price, T. J., & Dussor, G. O. (2016) · Pain · doi:10.1097/j.pain.0000000000000692 · Cited by 58 · see citing works
Langhnoja, J., Buch, L., & Pillai, P. P. (2020) · Cell Biology International · doi:10.1002/cbin.11500 · Cited by 57 · see citing works
Ferrini, F., Pérez-Sánchez, J., Ferland, S., Lorenzo, L.-É., Godin, A. G., Plasencia-Fernández, I., Cottet, M., Castonguay, A., Wang, F., Salio, C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17824-y · Cited by 57 · see citing works
White, A. O., Kramár, E. A., López, A. J., Kwapis, J. L., Doan, J., Saldana, D., Davatolhagh, M. F., Alaghband, Y., Blurton-Jones, M. M., Matheos, D. P., et al. (2016) · Nature Communications · doi:10.1038/ncomms11725 · Cited by 56 · see citing works
Nasrallah, P., Haidar, E. A., Stephan, J. S., Hayek, L. E., Karnib, N., Khalifeh, M., Barmo, N., Jabre, V., Houbeika, R. Y., Ghanem, A., et al. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100170 · Cited by 56 · see citing works
Jiang, N., Lv, J., Wang, H., Lü, C., Wang, Q., Xia, T., Bao, Y., Li, S., & Liu, X. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2019.09.007 · Cited by 56 · see citing works
Xu, J.-G., Li, S., Hua, X., Zheng, M., Wu, J., Ma, Z., Xing, X., Ma, J., & Shan, C. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.330617 · Cited by 55 · see citing works
Tillu, D. V., Hassler, S. N., Burgos-Vega, C., Quinn, T. L., Sorge, R. E., Dussor, G. O., Boitano, S. A., Vágner, J., & Price, T. J. (2015) · Pain · doi:10.1097/j.pain.0000000000000125 · Cited by 55 · see citing works
Chávez-Castillo, M., Núñez, V., Nava, M., Ortega, Á., Rojas, M., Bermúdez, V., & Rojas, J. (2019) · Advances in Pharmacological Sciences · doi:10.1155/2019/7943481 · Cited by 56 · see citing works
Brain-Derived Neurotrophic Factor, Nociception, and Pain
Merighi, A. (2024) · Biomolecules · doi:10.3390/biom14050539 · Cited by 54 · see citing works
Fischer, D. L., Kemp, C. J., Cole-Strauss, A., Polinski, N. K., Paumier, K. L., Lipton, J. W., Steece‐Collier, K., Collier, T. J., Buhlinger, D. J., & Sortwell, C. E. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2060-16.2017 · Cited by 54 · see citing works
Fujita, A., Fujita, Y., Pu, Y., Chang, L., & Hashimoto, K. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05346-5 · Cited by 53 · see citing works
Potential benefits of phytochemicals from Azadirachta indica against neurological disorders
Sandhir, R., Khurana, M., & Singhal, N. K. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105023 · Cited by 53 · see citing works
Neuroprotective Effects of Voluntary Exercise in an Inherited Retinal Degeneration Mouse Model
Hanif, A. M., Lawson, E. C., Prunty, M. C., Gogniat, M. A., Aung, M. H., Chakraborty, R., Boatright, J. H., & Pardue, M. T. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-16792 · Cited by 53 · see citing works
Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons
Sampathkumar, C., Wu, Y.-J., Vadhvani, M., Trimbuch, T., Eickholt, B. J., & Rosenmund, C. (2016) · eLife · doi:10.7554/elife.19374 · Cited by 51 · see citing works
Barfield, E. T., & Gourley, S. L. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.10.015 · Cited by 53 · see citing works
Zinc deficiency in rats is associated with up-regulation of hippocampal NMDA receptor
Doboszewska, U., Sowa-Kućma, M., Młyniec, K., Pochwat, B., Hołuj, M., Ostachowicz, B., Pilc, A., Nowak, G., & Szewczyk, B. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.09.013 · Cited by 52 · see citing works
The Expanding Therapeutic Potential of Neuronal KCC2
Tang, B. L. (2020) · Cells · doi:10.3390/cells9010240 · Cited by 52 · see citing works
BDNF receptor TrkB as the mediator of the antidepressant drug action
Casarotto, P. C., Umemori, J., & Ċastrén, E. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1032224 · Cited by 51 · see citing works
Chen, L., Gao, X., Zhao, S., Hu, W., & Chen, J. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000199 · Cited by 51 · see citing works
Jeon, S. J., Lee, H. J., Lee, H. E., Park, S. J., Gwon, Y., Kim, H., Zhang, J., Shin, C. Y., Kim, D. H., & Ryu, J. H. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.07.029 · Cited by 51 · see citing works
TrkB signalling pathway mediates the protective effects of exercise in the diabetic rat retina
Allen, R. S., Hanif, A. M., Gogniat, M. A., Prall, B. C., Haider, R., Aung, M. H., Prunty, M. C., Mees, L. M., Coulter, M. M., Motz, C. T., et al. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13909 · Cited by 51 · see citing works
Spaeth, A. M., Kanoski, S. E., Hayes, M. R., & Grill, H. J. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00025.2012 · Cited by 49 · see citing works
Brady, M. L., Pilli, J., Lorenz‐Guertin, J. M., Das, S., Moon, C. E., Graff, N., & Jacob, T. C. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.10.022 · Cited by 49 · see citing works
Targeting reactive astrogliosis by novel biotechnological strategies
Colangelo, A. M., Cirillo, G., Lavitrano, M., Alberghina, L., & Papa, M. (2011) · Biotechnology Advances · doi:10.1016/j.biotechadv.2011.06.016 · Cited by 48 · see citing works
Genome-Wide Association for Fear Conditioning in an Advanced Intercross Mouse Line
Parker, C. C., Sokoloff, G., Cheng, R., & Palmer, A. A. (2012) · Behavior Genetics · doi:10.1007/s10519-011-9524-8 · Cited by 47 · see citing works
- Authors
- Cazorla, M., Prémont, J., Mann, A., Girard, N., Kellendonk, C., & Rognan, D.
- Affiliations
- Inserm (FR)
- Laboratoire d'Innovation Thérapeutique (FR)
- Columbia University Irving Medical Center (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2011-05-02
- Volume
- 121
- Issue
- 5
- Pages
- 1846-1857
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3083767
- OpenAlex
- W2087102666
- Cited by
- 392
- References
- 50
- Citations by year
- 2026: 32 · 2025: 23 · 2024: 21 · 2023: 21 · 2022: 22 · 2021: 21 · 2020: 39 · 2019: 29 · 2018: 47 · 2017: 22 · 2016: 29 · 2015: 32 · 2014: 19 · 2013: 16 · 2012: 13
- FWCI
- 12.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Université de Strasbourg
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- TrkB receptor, brain-derived neurotrophic factor, ANA-12, anxiolytic effects, antidepressant effects, mood disorders, anxiety, depression, structure-based virtual screening, BDNF/TrkB signaling
- MeSH terms
- Animals, Antidepressive Agents, Anxiety, Azepines, Behavior, Animal, Benzamides, Brain, Chemistry, Pharmaceutical, Depression, Enzyme-Linked Immunosorbent Assay, Humans, Ligands, Molecular Weight, Neurons, Anti-Anxiety Agents, Drug Design, Signal Transduction, Brain-Derived Neurotrophic Factor, Mood Disorders, Receptor, trkB, Receptor, trkA, Mice
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